FDA Decisions: Amgen, Zealand Hit with CRLs in NSCLC, Congenital Hyperinsulinism

FDA Entrance_iStock, Grandbrothers

Pictured: FDA headquarters/iStock, Grandbrothers

The FDA approved 55 new drugs and 34 cell and gene therapies in 2023. But it’s not always good news that companies have to deliver to their stakeholders; the year also had its fair share of Complete Response Letters.

As we embark on 2024, BioSpace is committed to keeping you up-to-date on all the FDA’s actions in this FDA Decision Tracker.  


Dec 26:

Accelerated approval doesn’t always equal full clearance, something Amgen was reminded of when the FDA declined to convert Lumakras’ May 2021 conditional nod in KRASG12C-mutated non-small cell lung cancer (NSCLC) to a traditional one.

The decision likely didn’t come as a complete surprise to Amgen, as it followed a 10-2 advisory committee vote in October against the drug. The FDA’s Oncologic Drugs Advisory Committee argued that the data from the confirmatory Phase III CodeBreaK 200 study could not reliably be interpreted. Amgen will now be required to run an additional confirmatory study to be completed no later than February 2028, the company stated in a press release announcing the Complete Response Letter.

Dec 23:

The holidays didn’t get off to a happy start for Zealand Pharma, which received a Complete Response Letter for dasiglucagon, which the company intends to treat hypoglycemia in pediatric patients with congenital hyperinsulinism (CHI). The CRL is specifically for part one of the New Drug Application, in which Zealand sought approval for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with CHI for up to 3 weeks of dosing.

The CRL is related to deficiencies identified following an inspection at a third-party contract manufacturing facility, Zealand noted in a press release, adding that the deficiencies are not specific to dasiglucagon itself. The company intends to resubmit the NDA during the first half of this year after a successful reinspection of the manufacturing site.

Dec 21:

The FDA on Thursday signed off on the first and only self-administered treatment for polyneuropathy in hereditary transthyretin-mediated amyloidosis (hATTR-PN): AstraZeneca and Ionis’ eplontersen, now to be known as Wainua. The approval was granted based on data from the Phase III NEURO-TTRansform study, where treatment with Wainua significantly reduced serum concentrations of the transthyretin (TTR) protein and significantly improved neuropathy impairment.

Wainua is a ligand-conjugated antisense oligonucleotide therapy that works by tagging the TTR mRNA for degradation, reducing the overall production and concentration of the TTR protein. It can be self-administered with an auto-injector.

Dec 20:

The FDA on Wednesday granted full approval to Calliditas Therapeutics’ Tarpeyo (budesonide) delayed release capsules for adults with primary immunoglobulin A nephropathy (IgAN). Tarpeyo won accelerated approval in December 2021.

In the Phase III NefIgArd trial, patients treated with Tarpeyo saw significantly better kidney function, as measured by the estimated glomerular filtration rate (eGFR) versus placebo after nine months on the drug and 15 months of follow-up. After two years of treatment, patients receiving Tarpeyo saw 50% less deterioration in kidney function than those in the placebo arm.

According to Calliditas’ announcement, Tarpeyo is the only FDA-approved treatment for IgAN to significantly reduce the loss of kidney function.          

Dec 20:

Merck just can’t get gefapixant across the regulatory finish line. On Wednesday, the FDA issued a Complete Response Letter, stating that Merck’s data package “did not meet substantial evidence of effectiveness” for the treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults.

The rejection—Merck’s second in nearly two years—was not a complete surprise. Last month, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the evidence supplied by Merck did not show a clinically meaningful benefit in the intended population.

Merck will review the FDA’s letter and feedback to determine the next steps for gefapixant, according to Wednesday’s announcement of the CRL.

Dec 19:

A rare skin disease affecting young children has a new treatment. On Tuesday, the FDA approved Chiesi Global Rare Diseases’ Filsuvez (triterpenes) to treat wounds related to junctional epidermolysis bullosa (EB).

Filsuvez won approval based on data from the Phase III EASE study, where the drug led to accelerated wound healing, along with a reduction in overall wound burden and less pain associated with changing wound dressings.

Filsuvez, a topical herbal gel mixture containing dry extracts from two species—Betula pendula Roth and Betula pubescens Ehrh and hybrids of the two—was developed by Amryt Pharma, which Chiesi acquired in January of this year for $1.25 billion upfront.

Dec 18:

Inspection issues have, at least temporarily, quashed Checkpoint Therapeutics’ hopes of an approval for cosibelimab in metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). In a Complete Response Letter issued Monday, the FDA cited findings during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturer that the company will need to address in its resubmission, Checkpoint said in a press release.

Checkpoint is confident, however, that it will prevail next year. “As the only deficiencies relate to the FDA’s inspection of our third-party contract manufacturing organization, we believe we can address the feedback in a resubmission to enable marketing approval in 2024,” James Oliviero, the company’s president and CEO, said in a statement.

Dec 15:

This cancer collaboration just keeps on giving. On Friday, the FDA approved the combination of Merck’s Keytruda and Astellas and Pfizer/Seagen’s Padcev for the first-line treatment of locally advanced or metastatic urothelial cancer.

In a Phase III trial of 886 patients, Keytruda, a PD-1 inhibitor, plus Padcev, an antibody-drug conjugate, reduced the risk of death by 53% over platinum-based chemotherapy. Median overall survival was 31.5 months for the combo versus 16.1 months for chemotherapy. Median progression-free survival for Keytruda plus Padcev was 12.5 months compared to 6.3 months for chemo alone. These results were good enough for a very early approval—the companies’ supplemental Biologics License Application was accepted not three weeks ago on Nov. 30, when the FDA set a PDUFA date of May 9, 2024.

Dec 15:

On Friday, the FDA approved Zoryve (roflumilast) topical foam, developed by Arcutis Biotherapeutics to treat patients 9 years and older with seborrheic dermatitis. According to Arcutis’ press release, Zoryve is the first drug in more than two decades with a new mechanism of action for seborrheic dermatitis, a skin condition affecting primarily the scalp.

In the pivotal STRATUM trial, nearly 80% of individuals achieved the primary efficacy endpoint of Investigator's Global Assessment (IGA) Success, with just over 50% reaching complete clearance at week 8.

Seborrheic dermatitis, which affects more than 10 million people in the United States, is characterized by red patches covered with large, greasy, flaking yellow-gray scales and persistent itch, according to Arcutis.

Dec 14:

Merck scored a second approval for HIF-2α inhibitor Welireg (belzutifan), this one in advanced renal cell carcinoma (RCC). Specifically, Welireg is approved for RCC patients who have already been treated with a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. 

The approval is based on the Litespark-005 trial, where Welireg surpassed Novartis’ Afinitor (everolimus), Merck stated in a press release. Treatment with Welireg led to an objective response rate of 22% versus 4% for those treated with Afinitor. Welireg represents the first novel therapeutic class to be approved in advanced RCC since 2015, according to Merck.

Welireg was first approved in 2021 to treat adults with von Hippel-Lindau disease, a genetic condition that causes non-cancerous tumors in the body to grow.

Dec 14:

High-risk neuroblastoma (HRNB) patients now have an oral maintenance therapy option after the FDA greenlit US WorldMeds’ Iwilfin (eflornithine). Iwilfin is intended to reduce the risk of disease relapse in both adult and pediatric patients.

Iwilfin, an orally available inhibitor of ornithine decarboxylase, was approved based on the results of a single-arm study of children with HRNB who were initially treated with standard regimens, including immunotherapy. Results of the study showed an 84% event-free survival rate after four years compared with 73% in an external control arm. Overall survival after treatment with Iwilfin was 96% after four years versus 84% in the external control group.

Iwilfin led to a drop in expression levels of two oncogenic drivers—MYCN and LIN28B—both known to promote cell aging and prevent cancer development, according to the drug’s label.

Dec 8:

In an historic moment Friday, the FDA approved the first-ever gene therapy based on the Nobel Prize-winning CRISPR/Cas9 gene editing system discovered more than a decade ago by Jennifer Doudna and Emmanuelle Charpentier.

Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, has been hailed as curative for sickle cell disease (SCD) patients. Data from a pivotal Phase I/II/III trial and long-term safety and efficacy study together showed the therapy could significantly lessen severe vaso-occlusive events and hospitalizations. Vertex and CRISPR have priced Casgevy at $2.2 million.

SCD patients got not one but two new therapies Friday—the first gene therapies for the disorder caused by a mutation in the genes involved in producing hemoglobin beta—when the FDA approved bluebird bio’s Lyfgenia nearly two weeks ahead of its Dec. 20 action date. Lyfgenia (lovo-cel), a lentiviral gene therapy, led to complete resolution of vaso-occlusive events in 28 of 32 patients. Bluebird has set a list price of $3.1 million for Lyfgenia.

Dec 5:

Another rare disease saw an FDA approval Wednesday as the regulator approved Novartis’ Fabhalta (iptacopan) for paroxysmal nocturnal hemoglobinuria (PNH).

Fabhalta inhibits Factor B, which plays a key role in the proximal alternative pathway of the complement cascade. In PNH, heightened activity of the complement system prematurely destroys red blood cells, causing symptoms such as anemia and thrombosis. In a Phase III study, 82.3% of patients—who had residual anemia after anti-C5 treatment—saw a sustained increase in hemoglobin levels even without transfusions compared with 0% of those who stayed on anti-C5 treatments.

As of Dec. 4, 37 rare disease treatments had been approved by the FDA in 2023, according to stats provided to BioSpace by the National Organization for Rare Disorders.

Dec 1:

Eli Lilly can add two more indications for Jaypirca (pirtobrutinib) as the FDA greenlit the reversible Bruton's tyrosine kinase (BTK) inhibitor for chronic lymphocytic leukemia or small lymphocytic leukemia. Jaypirca is specifically intended for adults who have undergone at least two prior lines of therapy, including another BTK inhibitor and a BCL-2 inhibitor.

Jaypirca was first approved for relapsed or refractory mantle cell lymphoma in January. That approval broke new ground, as Jaypirca was the first-ever reversible BTK inhibitor to be authorized by the FDA. It is still the only such drug on the market.


Nov 27:

SpringWorks Therapeutics and people with desmoid tumors—a rare type of non-cancerous tumor that can be locally aggressive—have a new treatment to be thankful for. On Monday, the FDA approved nirogacestat, to be marketed as Ogsiveo, as the first-ever therapy for this potentially painful and physically debilitating condition.

In a pivotal trial of 142 adult patients with progressing desmoid tumors not amenable to surgery, Ogsiveo elicited “clinically meaningful and statistically significant improvement” in the primary endpoint of progression-free survival compared to placebo. An additional efficacy measure, objective response rate, was also statistically different, with 41% of patients receiving Ogsiveo seeing a response versus just 8% of those on placebo.

Nov 27:

As the company anticipated and warned investors last month in an SEC filing, the FDA on Monday rejected Aldeyra Therapeutics’ dry eye disease candidate. In a Complete Response Letter, the regulator stated that Aldeyra’s New Drug Application did not demonstrate “efficacy in treating ocular symptoms associated with dry eyes” and informed the company that “at least one additional adequate and well-controlled study” would be required to demonstrate efficacy.

Aldeyra has already submitted a Special Protocol Assessment for a crossover clinical trial and expects to hear FDA feedback on the plan in December. Depending on this feedback and assuming that the results of this trial are positive, Aldeyra intends to resubmit the NDA during the first half of 2024.  

Nov 17:

AstraZeneca scored a first-in-class approval for its pan-AKT inhibitor capivasertib as a treatment for adults with hormone receptor–positive and HER2-negative locally advanced or metastatic breast cancer whose tumors also have PIK3CA, AKT1 or PTEN mutations. Dubbed Truqap, the new treatment is approved in combination with Astra’s Faslodex.

The FDA’s green light was based on results from the Phase III CAPItello-291 where the combination cut the risk of disease progression or death by half compared to Faslodex alone.

“The rapid U.S. approval of Truqap reinforces the important role of the PI3K/AKT/PTEN pathway in HR-positive breast cancer and the critical need to test patients at the time of diagnosis, as up to fifty percent have tumors with these alterations,” Dave Fredrickson, executive vice president of Astra’s oncology business unit, said in a prepared statement.

Nov 17:

Astellas and Pfizer won FDA approval Friday for Xtandi, an androgen receptor signaling inhibitor, to treat nonmetastatic castration-sensitive prostate cancer (nmCSPC). Xtandi—which is also approved for four other types of prostate cancer—is the first androgen receptor signaling inhibitor authorized to treat nmCSPC with biochemical recurrence at high risk for metastasis, according to the companies’ announcement.

The supplemental approval was granted based on data from the Phase III EMBARK trial, which studied Xtandi plus leuprolide, placebo plus leuprolide (a synthetic hormone regulator) and Xtandi as a monotherapy. After five years, patients treated with the combination had a metastasis-free survival of 87.3%. This was compared to 80% in the Xtandi monotherapy arm and 71.4% in the leuprolide-only cohort.

Nov 16:

Merck’s Keytruda racked up another indication Thursday, this time for the first-line treatment of stomach cancer. Specifically, Keytruda was approved in combination with chemotherapy to treat adults with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The approval marks the seventh for the anti-PD-1 superstar in gastrointestinal cancer and its 38th overall in the U.S.

The first-line nod was given based on data from the Phase III KEYNOTE-859 study, where the Keytruda-based regimen cut the risk of death by 22% versus chemotherapy alone. Median survival was just over a month longer with Keytruda treatment at 12.9 months versus 11.5 months.

Nov 15:

Patients with ROS1-positive non-small cell lung cancer have a new treatment option after the FDA approved Bristol Myers Squibb’s Augtyro (repotrectinib) on Wednesday. A particularly aggressive form of lung cancer, ROS-positive NSCLC is difficult to treat and can often spread to the brain.  

In the pivotal TRIDENT-1 study, Augtyro, a tyrosine kinase inhibitor (TKI) targeting ROS1 oncogenic fusions, led to an objective response rate of 79% in TKI-naive patients. Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy, the ORR was 38%. The median duration of response (mDOR) for TKI-naive patients was 34.1 months and 14.8 months for the pretreated group.

Nov 15:

Patients with kidney failure receiving chronic hemodialysis are vulnerable to contracting catheter-related bloodstream infections. On Wednesday, the FDA greenlit a treatment designed to reduce these infections: CorMedix’s DefenCath, a combination of the amino acid derivative taurolidine and the anticoagulant heparin.

In a Phase III trial, DefenCath lowered the incidence of catheter-related bloodstream infections by 71% versus heparin alone. The efficacy results were so impressive that an Independent Data Safety and Monitoring Board recommended the study’s early termination.

It has not been an easy path to the finish line for CorMedix, which was previously turned away twice by the FDA. Both Complete Response Letters were due to manufacturing and supplier issues. CorMedix expects DefenCath to be available in the inpatient setting in the first quarter of 2024.

Nov 9:

Thursday, the FDA approved Valneva’s Ixchiq as the first vaccine to prevent disease caused by the chikungunya virus. Ixchiq is intended for adults at increased risk of exposure to the virus, which is typically transmitted through the bite of an infected mosquito. Those at highest risk live in the tropical and subtropical regions of Africa, Southeast Asia and parts of the Americas, according to the FDA’s announcement.

Safety of Ixchiq was demonstrated in two clinical studies made up of approximately 3,500 participants; in one study, around 1,000 people received a placebo. The most common side effects included headache, fatigue, muscle pain and joint pain. Efficacy was based on a U.S. study of 266 people who received Ixchiq versus 96 on placebo. Protective antibody levels were shown in non-human primates that had received blood from people who had been vaccinated. The FDA reported that “almost all vaccine study participants achieved this antibody level.”

Nov 9:

Takeda is having a big week. One day after winning approval of colorectal cancer drug Fruzaqla, the Japanese pharma announced the FDA approval of Adzynma for congenital thrombotic thrombocytopenic purpura (cTTP). Adzynma is approved as either a preventive or on demand enzyme replacement therapy for adult and pediatric patients with cTTP.

A very rare, inherited disorder, cTTP is caused by a disease-causing mutation in the ADAMTS13 gene, which is responsible for making the ADAMTS13 enzyme that regulates blood clotting. Adzynma, a purified recombinant form of this enzyme, provides a replacement for the low levels of the deficient enzyme in patients with cTTP. Thursday’s approval marks the first treatment for this patient population.

Nov 8:

Wednesday turned out to be a big day at the FDA. Hours after greenlighting Eli Lilly’s obesity treatment Zepbound, the regulator approved Takeda’s Fruzaqla (fruquintinib) for previously treated patients with metastatic colorectal cancer. Fruzaqla targets the VEGF-1, -2 and -3 receptors, which together play a crucial role in the formation of the blood vessels that sustain tumors. The drug’s strong selectivity allows for higher doses while minimizing off-target effects for sustained inhibition of its targets.

The approval, which came 20 days before Takeda’s scheduled PDUFA date, makes Fruzaqla the “first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status,” according to the Japanese pharma.

Nov 8:

A new chapter opened Wednesday in the obesity treatment space as the FDA approved Eli Lilly’s Zepbound (tirzepatide) injection for chronic weight management in adults with obesity or excessive weight with at least one weight-related condition, such as hypertension, type 2 diabetes (T2D) or high cholesterol. Tirzepatide, the active ingredient in Zepbound, is already approved in Lilly’s Mounjaro for T2D.

Zepbound is the first and only approved treatment activating two incretin hormone receptors, GIP and GLP-1, to tackle an underlying cause of excess weight, according to Lilly’s announcement. Zepbound won approval on the strength of the Phase III SURMOUNT-1 and SURMOUNT-2 trials, where patients taking Lilly’s drug saw a “statistically significant” reduction in body weight compared to their placebo counterparts. The Indianapolis–based pharma intends to make Zepbound available in the U.S. by the end of this year.

Nov 1:

Erosive GERD patients have a new treatment option after the FDA greenlit Phathom Pharmaceuticals’ Voquezna (vonoprazan) tablets—which the gastrointestinal-focused company claims is the “first major innovation to the U.S. erosive GERD market in over 30 years.”

Approval of Voquezna—a novel, oral small molecule potassium-competitive acid blocker—was granted based on results of the Phase III PHALCON-EE study, which compared the drug to the acid-reducer lansoprazole in terms of healing and maintenance of erosive GERD and associated heartburn symptom relief. Voquezna met the study’s primary endpoint of non-inferiority after eight weeks of treatment and showed a healing rate of 93% compared to 85% for lansoprazole.

Nov 1:

Merck’s blockbuster Keytruda racked up another FDA approval Wednesday, as the company announced that the anti-PD-1 therapy is now authorized—in combination with gemcitabine and cisplatin—to treat patients with locally advanced unresectable or metastatic biliary tract cancer (BTC). BTC is the sixth U.S. GI cancer indication for Keytruda, which is also approved for esophageal or gastroesophageal cancer and HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, among others.

Approval in BTC was granted based on results of the Phase III KEYNOTE-966 trial, where Keytruda elicited a “significant overall survival benefit” in this patient population versus chemotherapy alone, according to Merck’s announcement. Keytruda reduced the risk of death by 17% over chemo alone, with patients on the Keytruda plus chemo regimen surviving for a median 12.7 months versus 10.9 months for those receiving chemotherapy alone.


Oct 31:

Novartis picked up another indication for Cosentyx Tuesday as the FDA greenlit the IL-17A inhibitor to treat severe hidradenitis suppurativa, a painful, chronic skin condition characterized by boil-like lumps that typically burst into open wounds, leaving lasting scars. The approval marks the first new biologic treatment option for HS in almost a decade, according to Novartis’ announcement.

The approval was based on data from the SUNSHINE and SUNRISE studies, which together showed that Cosentyx-treated patients achieved significantly higher rates of clinical response compared to placebo. Safety was consistent with that observed in the plaque psoriasis trials, which Novartis said affirmed Cosentyx’s “differentiated safety profile.”

Oct 31:

J&J has new competition in the inflammatory disease space after the FDA approved Amgen’s Wezlana (ustekinumab-auub) for multiple such conditions. Wezlana is a biosimilar to and interchangeable with J&J’s Stelara and like Stelara, is approved to treat moderate to severe plaque psoriasis, active psoriatic arthritis, moderately to severely active Crohn's disease and moderately to severely active ulcerative colitis. In the pediatric setting, Wezlana can be used to treat patients six and older with active psoriatic arthritis and moderate to severe plaque psoriasis.

On the safety side, Wezlana’s label lists infection as its most serious side effect and recommends discontinuing treatment in case of serious or clinically significant infections. As with other ustekinumab products, Wezlana carries the risk of malignancies, hypersensitivity reactions and non-infectious pneumonia.

Oct 27: 

Coherus BioSciences and Shanghai Junshi Biosciences won approval Friday for Loqtorzi (toripalimab-tpzi)—in combination with cisplatin and gemcitabine—for the first-line treatment of metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC). This marks the first FDA-authorized treatment for NPC, a rare cancer. Loqtorzi is also approved as a monotherapy for adult patients with recurrent, unresectable or metastatic NPC with disease progression on or after platinum-containing chemotherapy.

The approval is based on the Phase III JUPITER-02 study where Loqtorzi combined with chemotherapy “significantly improved” progression-free survival, reducing the risk of disease progression or death by 48% compared to chemo alone. In terms of overall survival, treatment with Loqtorzi led to a 37% reduction in risk of death versus chemo alone.

Oct 27:

Roche’s Genentech can add a third indication to Vabysmo’s label after the FDA signed off on the bispecific antibody to treat macular edema—swelling—following retinal vein occlusion (RVO). Vabysmo is also approved for age-related macular degeneration and diabetic macular edema. It is the first and only bispecific antibody approved for the eye, according to Genentech’s announcement.

In the Phase III BALATON and COMINO studies, treatment with Vabysmo led to early and sustained improvement in vision in people with branch and central RVO, Genentech reported, which met the primary endpoint of non-inferior visual acuity gains at 24 weeks compared to Regeneron’s Eylea (aflibercept). Vabysmo’s safety profile was consistent with earlier trials, though Genentech noted that information on “rare post-marketing reports of retinal vasculitis and/or retinal vascular occlusion” has been added to the drug’s label across indications.

Oct 26:

There’s a new treatment on the immediate horizon for patients with Duchenne muscular dystrophy after the FDA approved Santhera Pharmaceuticals’  vamorolone—now Agamree. An oral suspension drug, Agamree is indicated for DMD patients two years and older.

Patients with DMD are typically treated with glucocorticoid regimens, which, while effective at slowing muscle deterioration, come with significant side effects. Agamree elicits “differential effects” on glucocorticoid and mineralocorticoid receptors, modifying their downstream activities. This allows it to maintain the usual efficacy of glucocorticoid regimens while also achieving a better-tolerated side effect profile, according to Catalyst Pharmaceuticals, which will commercialize the drug in North America. Catalyst CEO Patrick McEnany touted Agamree’s “transformational potential” for DMD patients.

While Agamree’s label does not carry a boxed warning, it does list precautions regarding alterations in endocrine, cardiovascular and renal function, immunosuppression and ophthalmic side effects, among others.

Oct 26:

Eli Lilly won FDA approval Thursday for Omvoh (mirikizumab-mrkz) for the treatment of moderately to severely active ulcerative colitis (UC), marking the company’s first approved drug for a type of inflammatory bowel disease. Omvoh—which is the second new treatment option for UC patients approved this week after Celltrion’s Zymfentra—is the first to selectively target the p19 subunit of IL-23, which plays a role in inflammation related to the condition, according to Lilly.

Omvoh hit both primary and key secondary endpoints in its pivotal trials, including sustained clinical remission, and Lilly noted that the drug delivered “significant improvement in bowel urgency,” which patients reported as one of the most disruptive symptoms of UC.

Oct 24:

Servier on Tuesday won its fifth FDA approval for Tibsovo (ivosidenib tablets)—which also happens to be the first and only targeted therapy for patients with relapsed or refractory (R/R) myelodysplastic syndromes (MDS) with a susceptible IDH1 mutation. Tibsovo is joined in this indication by a companion diagnostic, Abbott Laboratories’ RealTime IDH1 Assay—also approved Tuesday—which physicians can use to identify patients eligible for Tibsovo treatment.

Tibosovo’s approval was supported by data from a pivotal Phase I open-label study of 18 patients from the target population, where the drug elicited a 38.9% complete remission rate after a median of 1.9 months. The objective response rate in the study was 83.3% and median overall survival was 35.7 months; median duration of complete response had not been reached at the time of the data cutoff.

Oct 23:

Ulcerative colitis (UC) and Crohn’s disease (CD) patients who have previously used intravenous infliximab now have a subcutaneous option after the FDA approved Celltrion’s Zymfentra on Monday. Zymfentra is the first and only subcutaneous version of infliximab for the maintenance treatment of adults with inflammatory bowel disease, according to Celltrion.

Infliximab, approved in 1998 and marketed by J&J’s Janssen under the name Remicade, is a monoclonal antibody that works by blocking the pro-inflammatory cytokine TNF-alpha. In the Phase III LIBERTY-UC and LIBERTY-CD studies, Zymfentra elicited higher rates of clinical remission than placebo in patients with moderate-to-severe UC and CD, respectively, following induction with intravenous infliximab.

Oct 20:

Nearly two years ago, the FDA approved BioMarin’s Voxzogo (vosoritide) as the first therapy for achondroplasia, a rare genetic disorder that causes the most common form of dwarfism—fueling ongoing controversy within the dwarfism community about such treatments. That approval was for children five and older. On Friday, the FDA expanded Voxzogo’s label to include kids under five.

Voxzogo is designed to increase linear growth in pediatric patients with achondroplasia who have open growth plates. Friday’s supplemental approval enables Voxzogo to be prescribed to all children with open growth plates, the California–based company said in its announcement. Accelerated approval was granted based on an “improvement in annualized growth velocity,” according to BioMarin.

Oct 20:

Sanofi and Regeneron suffered a rare defeat with Dupixent this weekend as the FDA issued a Complete Response Letter to their supplemental Biologics License Application in chronic spontaneous urticaria, an inflammatory skin condition that leads to debilitating hives.

In its rejection, the regulator said additional efficacy data are required to support an approval. No safety or manufacturing issues were noted. Sanofi and Regeneron are running an ongoing study which they expect to provide this data, the pharma partners said in their announcement. Results of this study are expected late next year.

Oct 20:

Pfizer’s vaccines business got a boost on Friday as the FDA greenlit Penbraya as the “first and only vaccine” covering the five most common serogroups causing meningococcal disease in adolescents and young adults 10 to 25 years of age.

Annaliesa Anderson, Pfizer’s senior vice president and head of vaccine research and development, touted the benefits of Penbraya—which combines components from two other meningococcal vaccines, Trumenba and Nimenrix—saying the new vaccine “has the potential to protect more adolescents and young adults from this severe and unpredictable disease by providing the broadest meningococcal coverage in the fewest shots.”

Approval for Penbraya was granted based on positive results from Phase II and III trials, including a Phase III study that sought to determine the immunologic noninferiority of the vaccine against meningococcal vaccines currently available in the U.S. in terms of safety, tolerability and immunogenicity.

Oct 18:

The gene therapy space celebrated another first on Wednesday, as the FDA cleared the way for the first-ever investigational in vivo CRISPR-based gene editing therapy to enter late-stage development. Intellia’s NTLA-2001, being developed along with partner Regeneron for the genetic liver disease transthyretin (ATTR) amyloidosis cardiomyopathy, is expected to enter Phase III by the end of this year, Intellia announced.

Intellia and Regeneron made history in June 2021 with NTLA-2001 when they announced positive early data from the first-ever patients to have their DNA edited with an in vivo CRISPR/Cas9 therapy delivered systemically. 

Oct 18:

It’s been a charmed week for UCB, which on Wednesday announced its second straight approval, this one for bimekizumab—now Bimzelx—for adults with moderate-to-severe plaque psoriasis. Bimzelx is the first FDA-approved plaque psoriasis medication to inhibit both the IL-17A and IL-17F cytokines, each of which is a key player in the inflammatory cascade.

Bimzelx’s road to approval has not been without its trials. Its regulatory path was first interrupted by the COVID-19 pandemic; UCB reported in October 2021 that the FDA had to delay its verdict on the drug’s Biologics License Application because it was unable to conduct on-site facility inspections due to travel restrictions. Then, in May 2022, UCB received a Complete Response Letter that cited “pre-approval inspection observations” the company would need to address before Bimzelx could be approved.

Oct 17:

A long road for Ardelyx’s tenapanor ended in victory Tuesday as the FDA approved the phosphate absorption inhibitor to reduce serum phosphorus levels in patients with chronic kidney disease (CKD). Specifically, tenapanor—to be marketed as Xphozah—is intended for CKD patients on dialysis who have previously shown an inadequate response to phosphate binders or who are otherwise intolerant of such therapies.

Xphozah’s path has not been without challenges. In July 2021, the FDA issued Ardelyx a Complete Response Letter in which it stated that the molecule’s effect size was “small and of unclear clinical significance.” Then, in November 2022, an FDA advisory committee voted 9-4 that Xphozah’s benefits outweighed its risks. Ardelyx’s revamped New Drug Application included data from the Phase III PHREEDOM, BLOCK and AMPLIFY studies, all of which met their primary efficacy endpoints.

Oct 17:

The FDA signed off on the first once-daily subcutaneous targeted C5 complement inhibitor for generalized myasthenia gravis (gMG) in the form of UCB’s zilucoplan, now Zilbrysq. It is also the only once-daily target therapy for gMG that patients can self-administer for the rare autoimmune disease, according to UCB’s announcement.

Zilbrysq won approval based on the Phase III RAISE study, which assessed the therapy in adults with anti-acetylcholine receptor antibody-positive gMG. Zilbrysq demonstrated “rapid, consistent and statistically significant benefits” after 12 weeks in various patient- and clinician-reported outcomes, according to UCB. Zilbrysq’s label comes with a boxed warning for serious meningococcal infections, as “life-threatening and fatal episodes” of these infections have been observed with other C5 complement inhibitors. UCB noted that there have been no life-threatening or fatal meningococcal infections in patients treated with Zilbrysq to date.

Oct 16:

Patients with early-stage non-small cell lung cancer (NSCLC) can now rely on just one drug—Merck’s Keytruda—before and after surgery, in addition to chemotherapy during pre-surgical treatment, after the FDA approved the blockbuster Monday as a continuous regimen for these patients.

Approval was based on data from the KEYNOTE-671 trial, where Keytruda plus chemotherapy showed an advantage over placebo plus chemo in both overall survival and investigator-assessed event-free survival. Neither indicator was reached for patients taking Keytruda, while those on placebo survived an average of 52.4 months, with an event-free survival time of 17 months.

The approval is the sixth for Keytruda in NSCLC, according to Merck, which made the announcement Monday evening.

Oct 14:

Bristol Myers Squibb can add another adjuvant indication to Opdivo’s label after the FDA approved the immunotherapy blockbuster to treat patients 12 and older with completely resected stage IIB or IIC melanoma. According to BMS’ announcement, Opdivo is the only PD-1 inhibitor indicated for both this patient population and for stage III and stage IV completely resected melanoma.

The approval was granted based on the results of the Phase III CheckMate -76K trial, where Opdivo reduced the risk of recurrence, new primary melanoma or death by 58% compared to placebo. After one year of treatment with Opdivo, recurrence-free survival was 89% compared with 79% for placebo.

Oct 13:

Pfizer’s $6.7 billion acquisition of Arena Pharmaceuticals paid off in a big way Friday as the FDA approved etrasimod to treat moderate to severe ulcerative colitis (UC). Etrasimod—which will henceforth be known as Velsipity in this indication—was the centerpiece of Pfizer’s 2021 pick-up of Arena.

The approval was based on results from Pfizer’s ELEVATE UC Phase III registrational program. In May 2022, Pfizer announced data from two pivotal trials of the selective sphingosine 1-phospate (S1P) receptor modulator. The 52-week ELEVATE UC 52 study showed 27% clinical remission in patients taking Velsipity versus 7.4% in those who were part of the placebo group at week 12, and 32.1% clinical remission compared with 6.7% at week 52. In ELEVATE UC 12, clinical remission was 24.8% in those who received Velsipity compared to 15.2% in those who were given a placebo.

Velsipity’s label notes that the drug may increase the risk of infections and cause bradyarrhythmia and atrioventricular conduction delays. Velsipity showed a “favorable safety profile” across the Phase III program, according to Pfizer’s approval announcement.

Oct 12:

Alvotech has been iced out by “deficiencies” at the company’s manufacturing facility in Reykjavik, Iceland, which the FDA cited in a Complete Response Letter it issued in response to Alvotech’s bid for approval of AVT04. The company was proposing AVT04 as a biosimilar to J&J’s Stelara (ustekinumab), which binds to binds to two cytokines, IL-12 and IL-23, that are involved in inflammatory and immune responses. 

The deficiencies, which were identified via an FDA inspection of the Reykjavik facility that concluded in March, “must be satisfactorily resolved before the application can be approved,” Alvotech noted in its announcement. No other issues were flagged, according to Alvotech. The company plans to file a resubmission “shortly,” which it said would trigger another six-month review cycle and a new target action date.

Oct 12:

PepGen’s Phase I myotonic dystrophy type 1 (DM1) trial is cleared to begin in the U.S. after the FDA lifted a full clinical hold it had placed on the Investigational New Drug Application for PGN-EDODM1. PepGen announced the hold in May but did not provide details as to the reason for it.

“We have worked closely with the FDA to resolve their questions expeditiously and are pleased that the clinical hold on our DM1 program in the United States has been lifted,” PepGen president and CEO James McArthur said in Thursday’s press release.

The Phase I trial will study target dose levels of 5 mg/kg, 10 mg/kg and 20 mg/kg of PGN-EDODM1, with safety, transcript splicing and clinical outcome measures data from the 5 mg/kg cohort expected in 2024.

Oct 12:

The FDA greenlit Pfizer’s Braftovi (encorafenib)/Mektovi (binimetinib) combination for the treatment of adult patients with non-small cell lung cancer (NSCLC) with a BRAF V600E mutation as confirmed by an FDA-approved test.

“BRAF V600E mutations identify a unique subtype of metastatic non-small cell lung cancer that presents an actionable biomarker that precision medicines like [the Braftovi/ Mektovi] combination therapy can help address,” said Gregory Riely, vice chair of clinical research in the Department of Medicine at Memorial Sloan Kettering Cancer Center and a PHAROS investigator, in a prepared statement.

The approval was based on data from the ongoing Phase II PHAROS clinical trial, which is studying the combination in both treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. The trial met the major efficacy outcome measures of objective response rate and duration of response in both treatment groups, according to Pfizer’s announcement. 

Oct 9:

In a relatively rare move, the FDA went against the recommendation of one of its advisory committees, rejecting a bid by Alnylam to expand Onpattro (patisiran)’s label to cardiomyopathy of transthyretin-mediated amyloidosis. In September, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-3 in patisiran’s favor, but on Monday, Alnylam announced that the regulator had issued a Complete Response Letter in response to its supplemental New Drug Application in this indication. In the CRL, the FDA said Alnylam had not provided enough evidence of the therapy’s benefit.

In the same announcement, Alnylam said it would no longer work toward an expanded label for the siRNA therapeutic in cardiomyopathy of ATTR amyloidosis in the U.S.

Oct 6:

People with a range of rheumatic diseases have a new treatment delivery option after the FDA approved an intravenous formulation of Novartis’ IL-17A antagonist Cosentyx (secukinumab). The new authorization covers existing indications for Cosentyx, including ankylosing spondylitis (AS), psoriatic arthritis (PsA) and non-radiographic axial spondyloarthritis (nr-axSpA). A fully human monoclonal antibody, Cosentyx, which works by targeting and inhibiting the IL-17A cytokine, thereby suppressing the inflammatory pathway, was previously only authorized as a subcutaneous treatment in these indications.

The IV route of administration will improve treatment access for “a significant portion of patients” with AS, PsA and nr-axSpA who are not comfortable with self-injections or simply prefer to receive treatments in their healthcare provider’s office, said Philip Mease, clinical professor at the University of Washington School of Medicine, in a prepared statement.

Oct 6:

Arcutis Biotherapeutics is adding another indication for its psoriasis cream, Zoryve, after the FDA approved the company’s supplemental New Drug Application (sNDA) to expand the treatment for children ages 6 to 11. Zoryve is a once-daily, steroid-free cream, an option that Adelaide A. Hebert, professor and chief of pediatric dermatology at McGovern Medical School at UTHealth Houston and Children’s Memorial Hermann, said in a statement is “especially needed for managing plaque psoriasis in younger children.” 

Zoryve won approval in July 2022 to treat patients psoriasis patients 12 years and older. 

Oct 5:

Amgen has “interpretation” issues—of the confirmatory study variety, at least according to an FDA advisory committee that voted against converting the accelerated approval of its oral G12C KRAS inhibitor Lumakras (sotorasib) to full approval in non-small cell lung cancer (NSCLC). In a 10-2 vote Thursday, the Oncologic Drugs Advisory Committee determined that progression-free survival (PFS) data from the Phase III confirmatory CodeBreaK 200 study could not be reliably interpreted. The advisers pointed to the high number of study dropouts, the small sample size and potentially biased behavior of the trial’s investigators.

Panelist Mark Conaway, a professor at the Division of Translational Research and Applied Statistics at the University of Virginia School of Medicine, said that in CodeBreaK 200, there were “. . . a large number of issues that cloud the interpretation of a small observed effect.” 

Lumakras was approved under the FDA’s accelerated approval pathway in May 2021.

Oct 4:

The FDA’s Oncologic Drugs Advisory Committee voted 14-6 in favor of US WorldMeds’ neuroblastoma drug Wednesday—even without the benefit of a randomized controlled trial. The external advisers ultimately determined there was enough evidence to conclude that eflornithine hydrochloride (DFMO) boosts event-free survival in pediatric patients with high-risk neuroblastoma. In its application, US WorldMeds submitted data from a prospective Phase II, multicenter, open-label, single-arm study of DFMO maintenance treatment of patients who had completed multiagent and multimodality therapy.

While voting “yes,” Christopher Lieu, committee chairperson and director of the Gastrointestinal Medical Oncology Program at the University of Colorado, acknowledged that a positive decision could lead to a “slippery slope” in terms of the degree of clinical evidence that will be required of future drug applications in similar rare and difficult-to-study indications.

Oct 3:

The latest updated COVID-19 vaccine will soon be available in U.S. retail pharmacies and physicians’ offices after the FDA approved the 2023-2024 formulation of Novavax’s adjuvanted shot, NVX-CoV2601 under its Emergency Use Authorization pathway. The vaccine is also now included in the CDC’s recommendations, initially issued September 12. Doses of the updated vaccine will be available across the U.S. “in the coming days,” Novavax announced Tuesday. The EUA is for individuals 12 years and older. 

Oct 2:

Rocket Pharmaceuticals has lift-off in Leukocyte Adhesion Deficiency-I (LAD-I). The Cranbury, New Jersey–based biotech announced FDA acceptance of its Biologics License Application for RP-L201 (marnetegragene autotemcel), an investigational lentiviral vector (LV)-based gene therapy for LAD-I, a rare, genetic immune disorder that predisposes patients to frequent and often fatal infections. Without an allogeneic hematopoietic stem cell transplant, most patients do not live past childhood. Kinnari Patel, Rocket’s president and chief operating officer, noted that this treatment option “has substantial morbidity and mortality and may not be available in time for these children.” 

RP-L201 holds the FDA’s Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric, Fast Track and Orphan Drug designations.

Oct 2:

Adults and kids nine and older with primary hyperoxaluria type 1 (PH1)—a rare genetic disease—have a new treatment option after the FDA approved Novo Nordisk’s Rivfloza. The approval for Novo’s first RNAi therapy was based on data from the pivotal Phase II PHYOXTM2 trial and interim data from the ongoing Phase III PHYOXTM3 extension study. Rivfloza met the primary endpoint in PHYOXTM2 as patients in the treatment group saw a marked reduction from baseline in 24-hour-urinary oxalate (Uox) excretion from Day 90 to Day 180, according to Novo’s press release announcing the decision.

Primary hyperoxaluria causes an overproduction of oxalate by the liver. PH1, the most prevalent and severe subtype, primarily affects the kidneys and can lead to progressive kidney damage. It is estimated to affect more than 2,000 people in the U.S., according to Novo.

"RNA interference is a proven treatment approach for individuals with PH1,” David S. Goldfarb, clinical chief of the nephrology division at NYU Langone Medical Center and professor of medicine and physiology at NYU Grossman School of Medicine, said in the same press release. “With the approval of Rivfloza, we now have a novel treatment that lowers oxalate production safely and effectively.” 

Oct 2:

Eli Lilly will have to wait a little longer to see a payoff from lebrikizumab, which it picked up in its $1.1 billion acquisition of Dermira in January 2020. On Monday, the FDA issued a Complete Response Letter for lebrikizumab due to inspection findings at a third-party manufacturer. Lebrikizumab was being proposed to treat moderate-to-severe atopic dermatitis (eczema). The CRL did not cite any concerns about Lilly’s clinical data package, safety or label for lebrikizumab, according to a company press release.

In the statement, Patrik Jonsson, executive vice president, president of Lilly Immunology and Lilly USA, and chief customer officer, expressed confidence in lebrikizumab’s potential and said the company would continue to work closely with the unnamed third-party manufacturer and FDA in order to bring the drug to patients.


Sept 29:

On Friday, the FDA approved Biogen’s Tofidence as the first biosimilar to Roche’s Actemra (tocilizumab) in the U.S. Tofidence is authorized to treat moderately to severely active rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis.

The approval was based on a three-arm, parallel Phase I study that compared the pharmacokinetics, safety and immunogenicity of Tofidence to reference tocilizumab in healthy volunteers; a Phase III study compared the two products in RA not sufficiently controlled by methotrexate in order to establish equivalent efficacy and comparable pharmacokinetic, safety and immunogenicity profiles. 

To illustrate the value of a biosimilar in this space, Biogen referenced in its press release a report by the Association for Accessible Medicines which states that spending on therapies for autoimmune diseases has consistently increased by 10% to 25% each year over the past decade. “The entry of new biosimilar competition in 2023 and 2024 is projected to dramatically reduce this trend,” according to the report.

Sept 28:

Adults with late-onset Pompe disease (LOPD) have a new treatment option after the FDA approved Amicus Therapeutics’ Pombiliti (cipaglucosidase alfa-atga) plus Opfolda (miglustat). The treatment—the first and only two-component therapy for patients with LOPD—is specifically for individuals who are not their current enzyme replacement therapy. LOPD is a life-threatening lysosomal disorder caused by a deficiency of acid alpha-glucosidase (GAA). Pombiliti is a recombinant human GAA enzyme that is taken up into the muscle cells while Opfolda is an enzyme-stabilizer designed to stabilize Pombiliti in the blood.

Amicus intends to launch the treatment in the U.S. “immediately.”

The depression treatment space has had a landmark year with the August approval of Biogen and Sage Therapeutics’ Zurzuvae as the first pill for postpartum depression—though the drug was rejected for major depressive disorder (MDD). On Thursday, the FDA approved a new therapy for that indication in Fabre-Kramer Pharmaceuticals’ Exxua (gepirone hydrochloride tablets). 

The approval of Exxua—which Houston–based Fabre-Kramer states is the “first and only approved” antidepressant for adults with MDD that works through the selective agonism of 5HT1a receptors to modulate serotonin throughout the central nervous system—was hard won. The privately held company first filed for approval of the drug in September 1999 but the New Drug Application was rejected by the FDA in 2002.  Exxua’s label includes a boxed warning for suicidal thoughts and behaviors in children and young adults, for whom the drug is not approved. It does not, Fabre-Kramer notes, carry precautions for sexual dysfunction and weight gain. The company plans to launch Exxua in early 2024.

Sept 27:

Takeda on Wednesday won approval for a subcutaneous (SC) form of Entyvio as a maintenance therapy for adults with moderately to severely active ulcerative colitis (UC) following induction therapy with intravenous Entyvio. The SC treatment is expected to be available in the U.S. by the end of October as a single-dose pre-filled pen.  

Bruce Sands, chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, lauded the SC approval, saying he appreciates being able to provide “appropriate UC patients a choice of how they receive their maintenance therapy.” 

Entyvio, which is also under FDA review for severely active Crohn’s disease, was first approved in 2014.

After a long day of presentations and deliberations, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted overwhelmingly to reject BrainStorm Cell Therapeutics’ experimental amyotrophic lateral sclerosis (ALS) therapy NurOwn. With a tally of 17-1, the advisory committee (adcomm) determined that there was not substantial evidence that NurOwn, a cell therapy made up of mesenchymal stromal cells secreting neurotrophic factors (MSC-NTF), was an effective treatment for patients with mild to moderate ALS.

The outcome was not a surprise after FDA briefing documents released on Monday took issue with NurOwn’s manufacturing plan and said the company failed to demonstrate substantial evidence of efficacy in its Biologics License Application. BrainStorm filed the BLA using the FDA’s File Over Protest procedure after the regulator issued a Refuse to File letter in November 2022.

Ocuphire and Viatris won approval Wednesday for Ryzumvi (phentolamine ophthalmic solution) for the reversal of pharmacologically-induced pupil dilation. While the topical drug does not come with a boxed warning, its label does carry warnings for uveitis and other common adverse effects of treatment, including site discomfort and conjunctival hyperemia. The partners intend to launch Ryzvumi in the U.S. in the first half of 2024.

Artificial dilation can last from six to 24 hours, creating barriers for some patients. “Our hope is that by addressing patient dilation barriers, we're empowering eye care professionals to broaden exam availability, leading to enhanced eye health outcomes,” Viatris Eye Care division president Jeffrey Nau said in a prepared statement.

Sept 25:

Coherus BioSciences just can’t seem to catch a regulatory break this week. The company announced Monday that Udenyca Onbody, its updated biosimilar to Amgen’s Neulasta, has been rejected by the FDA due to an ongoing issue at a third-party filler. The Complete Response Letter did not note any issues with the biosimilar’s clinical efficacy or safety, trial design, labeling, drug substance manufacturing or device design or manufacturing, Coherus stated in a press release. Neulasta is used to prevent neutropenia, a lack of white blood cells caused by chemotherapy. 

In the same announcement, Coherus reported that in the process of inspecting three sites in China enrolling patients for two pivotal trials of its PD-1 antibody toripalimab in recurrent nasopharyngeal carcinoma (NPC), the FDA identified one “observation”. Toripalimab is being proposed as a first-line, second-line or greater treatment for metastatic or recurrent NPC. Coherus said the observation—communicated in an FDA Form 483—is readily addressable and the company “continues to anticipate potential approval for toripalimab by year end 2023."

Coherus and its partner Junshi Biosciences received a CRL for toripalimab in this indication requesting a “quality process change” in May 2022.

Sept 25:

Canadian biopharma company Appili Therapeutics announced the FDA approval of Likmez—formerly ATI-1501—a  liquid oral reformulation of the antibiotic metronidazole. With more than 10 million prescriptions filled annually in the U.S., metronidazole is a front-line oral antibiotic used commonly for parasitic and anaerobic bacterial infections, according to Appili’s website. Prior to the approval of Likmez, metronidazole was only available in tablet form, which posed therapeutic barriers for very young patients and those who have difficulties swallowing, especially the elderly. New York–based Saptalis Pharmaceuticals will commercialize Likmez in the U.S.

Located in Halifax, Nova Scotia, Appili is developing novel approaches to treat infectious diseases. Also in the pipeline are a topical product for the disfiguring skin infection cutaneous leishmaniasis and a live attenuated vaccine against aerosolized bacteria Francisella tularensis, which the National Institutes of Health defines as a Category A pathogen.

Sept 22:

Nearly two months after winning approval in the EU for Jardiance in chronic kidney disease (CKD), Eli Lilly and Boehringer Ingelheim can add CKD to the SGLT2 inhibitor’s label stateside too. The FDA nod, which the companies announced on Friday, is specifically for the reduction of risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease and cardiovascular death and hospitalization in adults with CKD at risk of progression.

The ”meaningful benefits” shown by Jardiance in the Phase III EMPA-KIDNEY trial “are welcome news for adults living with CKD in [the U.S.]," Katherine Tuttle, executive director for research at Providence Inland Northwest Health, regional principal investigator for the Institute of Translational Health Sciences, professor of medicine at the University of Washington, and a steering committee member for the trial, said in a prepared statement.

In EMPA-KIDNEY, which enrolled more than 6,600 patients, Jardiance combined with standard of care elicited a 28% relative risk reduction in kidney disease progression, defined as end-stage kidney disease, or cardiovascular death compared with placebo plus standard of care. Jardiance also met the trial’s secondary endpoint, showing a 14% reduction in the risk of first and recurrent hospitalization compared to placebo, a result that was deemed significant.

Sept 21:

In a setback for Intarcia Therapeutics, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously that the benefits of its drug-device combination for Type 2 diabetes, ITCA 650, did not outweigh the risks. The panel cited the high rate of acute kidney injury (AKI) in patients assigned to the treatment group, which it said could potentially be attributed to ITCA 650. The advisors concluded that there is a lot of uncertainty surrounding ITCA 650’s safety profile and that additional data are needed, which they suggested Intarcia could gather in larger trials.

Intarcia has walked a troubled regulatory path with ITCA 650, suffering two FDA rejections for ITCA 650. The first Complete Response Letter, in which the regulator cited manufacturing issues, came in 2017, and the FDA issued a second CRL in March 2022, flagging signals of AKI.

Sept 20:

The FDA surprised ARS Pharmaceuticals—if the tone of the company’s press release is any indication—by issuing a Complete Response Letter for neffy, an epinephrine nasal spray, in type 1 allergic reactions, including anaphylaxis. The regulator went against the recommendation of its Pulmonary-Allergy Drugs Advisory Committee (PADAC), which in May voted 16-6 in favor of the treatment in adults and 17-5 in kids 18 years and younger.

In its CRL announcement, ARS said it had aligned with the FDA on physician labeling and post-market requirements, which included a repeat-dose study of neffy under allergen-induced allergic rhinitis conditions. The agency is now requesting a repeat-dose study be completed before it will approve neffy. FDA is also asking that ARS submit additional information on testing for nitrosamine impurities based on new draft guidance that was issued after 
neffy’s New Drug Application was submitted in October 2022.

ARS intends to submit a Formal Dispute Resolution Request to appeal the CRL. The company plans to resubmit the application for neffy in the first half of next year and anticipates another FDA action date in the second half of 2024.

Sept 16:

After a three-month delay, the FDA handed GSK a victory Friday, approving momelotinib—to be henceforth known as Ojjaara—for the treatment of myelofibrosis with anemia. Ojjaara’s label is for adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis who suffer from anemia. The JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor is the only approved drug for both newly diagnosed and previously treated myelofibrosis patients with anemia to address key disease manifestations including anemia, constitutional symptoms and enlarged spleen, according to GSK’s press release.

“The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions,” said Nina Mojas, senior vice president of oncology global product strategy at GSK in the same press release.

By silencing the JAK1 and JAK2 pathways, momelotinib alleviates symptoms of splenomegaly and elicits improvements in patients’ constitution.

Sept 14: 

Iovance Biotherapeutics just can’t catch a break when it comes to the regulatory review of Lifileucel, its tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma. Originally anticipating an FDA decision on or before November 25, the San Carlos, Calif–based company will now have to wait until 2024 due to “resource constraints” on behalf of the regulator, Iovance announced Thursday.

Nearly three years ago, in October 2020, Iovance’s planned Biologics License Application was pushed back when the FDA requested additional data on Lifileucel’s potency assays. Then, in May 2021, the regulator requested more data on the potency assays. In March 2023, Iovance finally completed a rolling BLA submission, which the FDA accepted in May, setting the late November action date.

The new action date is February 24, 2024. Successful facility inspections have been completed and there have been no major review issues, according to Iovance’s press release. The FDA’s Center for Biologics Evaluation and Research is expecting an influx of cell and gene therapy applications, and in March 2023 established a new super office, the Office of Therapeutic Products, in an attempt to keep up with the demand.

Sept 14: 

After announcing Tuesday that its CRF1 antagonist, crinecerfont, met the primary efficacy endpoint in the Phase III CAHtalyst Adult Study for classic congenital adrenal hyperplasia, Neurocrine Biosciences reported good news on the neuro front. The FDA has accepted the San Diego–based company’s New Drug Application for Ingrezza (valbenazine) oral granules, a new sprinkle formulation of the capsules, which are approved to treat tardive dyskinesia and chorea associated with Huntington's disease. The oral granule capsules—which come in 40 mg, 60 mg and 80 mg doses—are intended to be opened and sprinkled on soft foods prior to administration. The FDA has set an action date of April 30, 2024. 

Sept 14:

Hemogenyx Pharmaceuticals could be headed to the clinic with its CAR-T therapy HEMO-CAR-T after announcing that the FDA has accepted its plan to address concerns that led the regulator to place it on a clinical hold in July 2023. In the review letter, the FDA cited a “splicing deficiency” that arises during the production of the lentivirus used to create the CAR-T cells for HEMO-CAR-T.

Hemogenyx responded in August with a “detailed plan” supported by laboratory tests to address the FDA’s comments, according to a press release issued Thursday. The company will resubmit the Investigational New Drug Application “as expeditiously as possible in order to move forward with clinical trials,” Hemogenyx CEO Vladislav Sandler said in the same press release. HEMO-CAR-T is being developed to treat acute myeloid leukemia.

Sept 13:

Alnylam won support from an FDA advisory committee Wednesday for patisiran as a treatment for adults with cardiomyopathy induced by transthyretin amyloidosis (ATTR-CM). The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-3 that patisiran’s benefits outweigh its risks in this indication, despite concerns expressed in FDA briefing documents prior to the adcomm meeting.

While Alnylam’s Phase III APOLLO-B study hit both key primary and secondary endpoints, the FDA stated in the documents that “the effects of patisiran compared to placebo on both endpoints were small, of questionable clinical meaningfulness, and may not be detectable by patients.” Major discussion points during the adcomm meeting included whether these key endpoints were appropriate to ascertain clinical meaningfulness in the ATTR-CM population, and panelists expressed varying opinions on whether the magnitude of the benefit seen in trial data was clinically meaningful. The FDA is set to render its decision on patisiran in ATTR-CM on or before Oct. 8, 2023.

Sept 13:

The FDA accepted for review Takeda’s Biologics License Application for a subcutaneous (SC) formulation of Entyvio for moderately to severely active Crohn’s disease following induction therapy with intravenous Entyvio. Takeda is supporting the BLA with data from the pivotal VISIBLE 2 Phase III trial, in which 409 adult patients experienced a clinical response—defined as a decrease of 70 points or more in Crohn’s Disease Activity Index (CDAI) score from baseline—following two doses of open-label IV Entyvio.

This marks the second BLA for SC Entyvio under FDA review, as the regulator accepted a BLA resubmission for the formulation for maintenance therapy in adults with moderately to severely active ulcerative colitis after IV Entyvio induction therapy in April 2023. The second submission was in response to a Complete Response Letter issued by the FDA in December 2019.

Sept 13:

Madrigal Pharmaceuticals—widely hailed as the leader in the nonalcoholic steatohepatitis (NASH) space—announced Wednesday that the FDA has accepted and granted priority review for its New Drug Application for resmetirom. The regulator set an action date of March 14, 2024, by which it must decide whether or not to approve the once daily, oral, thyroid hormone receptor (THR)-β selective agonist to treat NASH with liver fibrosis. In more good news for Madrigal, the FDA noted that it is not planning to hold an advisory committee meeting for the application. 

The Pennsylvania-based company is supporting the NDA with a clinical development program that consists of 18 studies, including four Phase III trials. In December, the company’s shares rocketed 209% when it announced that the candidate had hit both primary endpoints and a secondary endpoint in the Phase III MAESTRO-NASH biopsy trial. Madrigal is requesting approval of resmetirom under the FDA’s accelerated approval pathway.

Sept 11:

As the leaves begin to turn across the U.S., the first updated COVID-19 booster shots are here. The FDA on Monday approved shots from both Pfizer-BioNTech and Moderna, which are specifically formulated to provide protection against circulating Omicron-related variants, including subvariant XBB.1.5, which the regulator had recommended the shots be updated to cover. The new boosters are approved for individuals 12 and above, with Emergency Use Authorization given for children aged six months to 11 years. On Tuesday, the Centers for Disease Control and Prevention signed off on the boosters and recommended that everyone 6 months and above receive them as CDC data indicate that hospitalizations are ticking up across the country.

Sept 11:

Israel–based BioLineRx won FDA approval for Aphexda (motixafortide), a stem cell mobilization agent for patients with multiple myeloma scheduled for autologous stem cell transplantation (ASCT). Aphexda was approved in combination with filgrastim (G-CSF), a granulocyte colony-stimulating factor that stimulates the growth of neutrophils. The FDA nod is based on the Phase III GENESIS trial, which compared Aphexda plus filgrastim against placebo plus filgrastim. In a single apheresis session, one round of add-on Aphexda mobilized the optimal number of stem cells in around 90% of patients; just 10% of patients who received granulocyte-CSF with placebo reached a similar level of stem cell mobilization.

Aphexda is the first approved therapeutic for BioLineRx, which also has offices in Waltham, Mass.

Sept 8:

At the end of July, Citius Pharmaceuticals received a Complete Response Letter from the FDA pertaining to its Biologics License Application for Lymphir, an engineered IL-2-diphtheria toxin fusion protein intended to treat relapsed or refractory cutaneous T-cell lymphoma. Friday, the Cranford, New Jersey–based biopharma announced that the FDA has agreed with its plans to address the “requirements” outlined in the CRL. In its decision, the regulator told Citius it would need to incorporate enhanced product testing and additional controls that were agreed to during the market application review.

Citius is “encouraged by the constructive engagement with the FDA,” Leonard Mazur, the company’s chairman and CEO, said in a statement on Friday, adding that Citius plans to complete the “remediation activities” by the end of 2023 and file a resubmission early in 2024.

Sept 6:

AstraZeneca  will have to wait to add another indication to the label of blockbuster drug Ultomiris, as the FDA rejected the company’s supplemental application in neuromyelitis optica spectrum disorder (NMOSD),  a rare autoimmune disease particularly affecting the optic nerve.  

In its complete response letter, the regulator requested that AstraZeneca improve Ultomiris’ Risk Evaluation and Mitigation Strategy (REMS) strategy to further validate patients’ meningococcal vaccination status or prophylactic administration of antibiotics prior to treatment with the C5 complement inhibitor. The FDA did not cite any issues with Ultomiris’ efficacy or safety data from the Phase III CHAMPION-NMOSD trial. 

Sept 5:

The FDA gave tentative approval to Viatris’ abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg tablets to treat pediatric HIV patients. The nod came through President Joe Biden’s Emergency Plan for AIDS Relief (PEPFAR) program, and indicates that the formulation meets the FDA’s quality, safety and efficacy standards, according to Viatris’ press release. The Pennsylvania–based company has signed a licensing agreement for pediatric dolutegravir with the Medicines Patent Pool and a development agreement with ViiV Healthcare and the Clinton Health Access Initiative to produce and distribute the fixed-dose combination of abacavir/ dolutegravir/lamivudine.

While children account for 4% of people living with HIV, they made up 13% of AIDS-related deaths in 2022 due to a lack of antiretroviral therapy, Viatris stated in the same press release. 


Aug 30:

Outlook Therapeutics lost nearly three-quarters of its market share after the FDA declined to approve ONS-5010, an investigational ophthalmic formulation of the cancer drug bevacizumab being developed for wet age-related macular degeneration (AMD). In its complete response letter (CRL), the FDA cited “several CMC issues, open observations from pre-approval manufacturing inspections and a lack of substantial evidence,” according to Outlook.

The New Jersey–based biopharma intends to request a formal meeting with the FDA to “further understand the BLA deficiencies and how best to resolve them,” Russell Trenary, the company’s president and CEO, said in a statement. 

ONS-5010 is an ophthalmic formulation of bevacizumab, a VEGF inhibitor sold by Roche’s Genentech as Avastin for several types of cancer. In eye diseases, it prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage and the formation of new blood vessels in the retina.

Aug 29:

In what could be a major boon to its $4 billion–plus sales aspirations, BMS scored first-line status for Reblozyl in adult patients with anemia in low- to intermediate-risk myelodysplastic syndromes (MDS) who may require blood transfusions. First approved to treat MDS-related anemia in 2020 in patients who failed to respond to an erythropoiesis-stimulating (ESA) agent—the established front-line treatment—the treatment will now be available to patients who have not received ESA therapy.

The first-line nod was backed by interim data from the Phase III COMMANDS trial, which pitted Reblozyl against the ESA standard of care treatment, Amgen and Johnson & Johnson’s Epogen/Procrit. More than 58% of patients receiving BMS’s drug achieved transfusion independence versus 31% of the comparator. And while Reblozyl was previously only available to patients exhibiting ring sideroblasts—blood cells with iron deposits circling the nucleus—it is now approved to treat those with and without this common symptom. 

Aug 24: 

Sandoz, the generics and biosimilars arm of Novartis, has earned FDA approval for the first biosimilar drug to treat multiple sclerosis. Tyruko (natalizumab-sztn) is a biosimilar of Biogen’s treatment Tysabri (natalizumab), a monotherapy used to treat adults with relapsing forms of MS. The biosimilar is also approved to treat adults with Crohn’s disease, another approved indication for Tysabri. Both drugs come with the risk of opportunistic viral infection progressive multifocal leukoencephalopathy and will carry a boxed warning about the potentially severe complication.  

Aug 24: 

Gilead Sciences’ antiviral drug Veklury (remdesivir) earned a label expansion from the FDA, now cleared for COVID-19 patients with all stages of liver disease. The dose will be the same as it was for its originally approved uses in adult and pediatric patients with mild to moderate COVID-19 who are at high risk for progression to severe COVID-19. Veklury was the first drug to get full FDA approval for COVID-19. In July, the FDA approved another supplemental NDA that allowed it to be used across all stages of renal disease. 

The FDA based its expansion for all stages of liver disease on the data from a Phase I trial that showed no new safety signals. Hepatic laboratory testing is recommended for all patients and the drug may need to be discontinued if alanine transaminase levels hit 10 times the high end of the normal range or liver inflammation develops. 

Aug 21:

Pfizer’s respiratory syncytial virus vaccine Abrysvo won FDA approval for use in pregnant women to prevent RSV-associated lower respiratory tract disease in infants. Abrysvo is an unadjuvanted bivalent RSV prefusion F vaccine composed of two proteins that were selected specifically to optimize against the RSV A and B strains.

The vaccine was first approved in June 2023 for use in adults aged 60 years and above. However, the shot can now also be administered to pregnant women at 32 through 36 weeks of gestation to elicit immunity in their infants.

Data from the Phase III MATISSE trial supported the FDA’s approval. At the study’s prespecified interim analysis, Abrysvo had a vaccine efficacy of 81.8% for preventing medically attended severe RSV-associated lower respiratory tract disease (LRTD) 90 days after birth. This waned slightly to 69.4% at 180 days. The findings were published in The New England Journal of Medicine in April 2023.

Aug 18:

Neurocrine Biosciences got FDA approval to expand Ingrezza’s (valbenazine) label to include chorea in Huntington’s disease. Approved in 2017 to treat tardive dyskinesia, Ingrezza is a selective vesicular monoamine transporter 2 inhibitor.

In the company’s supplemental NDA, Neurocrine included data from the Phase III KINECT-HD trial and the ongoing KINECT-HD2 open-label study to establish the safety and efficacy of Ingrezza in the proposed indication. Data in a Lancet Neurology publication in May showed that Ingrezza treatment significantly reduced scores in the Unified Huntington’s Disease Rating Scale Total Maximal Chorea score by 3.2 units versus placebo, an effect that was statistically significant.

Ingrezza also outperformed placebo on secondary endpoints, including the Clinical Global Impression of Change and Patient Global Impression of Change response status. In clinical studies of Huntington’s disease, treatment-emergent adverse events included somnolence and sedation, urticaria, rash and insomnia.

Aug 18:

Regeneron Pharmaceuticals’ Veopoz (pozelimab) secured FDA approval as the first and only treatment indicated specifically for CHAPLE disease, also known as CD55-deficient protein-losing enteropathy, an ultra-rare hereditary disease that can cause potentially life-threatening gastrointestinal and cardiovascular symptoms. A fully human monoclonal antibody, Veopoz is approved for the treatment of adult and pediatric CHAPLE patients 1 year of age and older.

In February 2023, the FDA gave Priority Review to Regeneron’s investigational antibody, which works by binding to the C5 complement factor, thereby disrupting the complement cascade and preventing associated diseases. Regeneron presented Phase II/III data in its application for regulatory approval showing “rapid and sustained normalization” of albumin, one of the key markers of CHAPLE disease, in all 10 patients at 24 weeks. The treatment also eased symptoms such as increased bowel movements and abdominal pain.

Aug 18:

The FDA has expanded the label of Regeneron’s blockbuster eye therapy Eylea (aflibercept), allowing the administration of a higher 8-mg dose. Under the new high-dose regimen, Eylea injections will be given every four weeks for the first three months across all indications.

In diabetic retinopathy, the treatment can be administered every eight to 12 weeks thereafter, while the dosing interval can stretch up to 16 weeks in patients with wet age-related macular degenerationand diabetic macular edema. Eylea was previously approved in these indications but was limited to 2-mg doses.

Aug 16:

After two prior setbacks, Ipsen’s palovarotene finally earned FDA approval to treat fibrodysplasia ossificans progressive (FOP), the first treatment for the ultra-rare bone disease. Now to be sold under the brand name Sohonos, the oral medication is indicated for the reduction of heterotrophic ossification in adults and children with FOP.

The FDA approval is the culmination of a long and bumpy road for Ipsen’s FOP drug. The biotech first tried for an approval in 2021 but voluntarily withdrew its application in August of that year after the regulator asked for more data. Ipsen filed a resubmission a few months later, which the FDA rejected in December 2022 and requested additional information regarding the data that the company had already provided.

The FDA’s approval this week was backed by data from the Phase III MOVE trial, which according to Ipsen is the first and largest multicenter, open-label study in this space involving both adult and pediatric patients. In the trial, palovarotene reduced the annualized heterotrophic ossification by 54% compared with standard of care without introducing new safety signals. 

Aug 14:

Following a nearly decade-long effort, Delcath Systems finally won the FDA’s greenlight for its Hepzato Kit for the liver-directed treatment of adult patients with metastatic uveal melanoma. Hepzato is a drug-device combination of melphalan—a well-established chemotherapeutic agent—and the company’s Hepatic Delivery System, which can directly administer the drug to the liver.

Delcath first sought FDA approval in August 2012. More than a year later, in September 2013, the regulator rejected the application, asking the company to perform another well-controlled randomized trial to better determine the safety and efficacy of the investigational product. In February 2023, nearly 10 years later, Delcath resubmitted its NDA.

The application contained data from the Phase III FOCUS study, a single-arm, open-label trial which enrolled 91 patients who were treated every six to eight weeks for up to a maximum of six cycles. FOCUS found that the drug-device combination had an overall response rate of 36.3%, including seven complete responders and 26 partial responders, with treatment response lasting for a median of 14 months. Patients treated with Hepzato saw a 73.6% disease control rate.

Aug 14:

In what is expected to become a multibillion-dollar blockbuster, Pfizer’s BCMAxCD3 bispecific antibody Elrexfio (elranatamab-bcmm) has secured an FDA accelerated approval as another off-the-shelf treatment option for patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy. Elrexfio is being touted by Pfizer as the first off-the-shelf, ready-to-use fixed-dose subcutaneous therapeutic that targets the BCMA protein.

The FDA’s accelerated approval was supported by data from the Phase II MagnetisMM-3 study, which found that in heavily pretreated RRMM patients who had not yet received BCMA-directed therapy, Elrexfio had an overall response rate of 58%, with around 82% of responders maintaining improvements for at least nine months. In those with prior exposures to BCMA-directed therapies, Elrexfio elicited an overall response rate of 33%. The therapy comes with a boxed warning for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.

Aug 14:

Biotech company Revance Therapeutics has received its first therapeutic indication for Daxxify (daxibotulinumtoxinA-lanm) for the treatment of cervical dystonia in adults. Revance won approval based on data from the Phase III ASPEN 1 and ASPEN OLS trials in which Daxxify was found to be safe and effective at two separate injected doses with a median duration of effect of 24 and 20.3 weeks for the respective groups.

Daxxify, a neuromuscular blocking agent and acetylcholine release inhibitor that’s positioned as a rival to AbbVie’s Botox, was approved in September 2022 for the temporary improvement of moderate to severe frown lines in adults. According to Revance, the total U.S. therapeutic neuromodulator market opportunity for Daxxify is $2.5 billion, including the $345 million cervical dystonia market.

Aug 11:

J&J’s Janssen got the FDA’s greenlight for its PARP inhibitor Akeega (niraparib and abiraterone acetate), which is now authorized to treat BRCA-mutated metastatic castration-resistant prostate cancer. Akeega is the first dual-action tablet that combines the activity of a PARP inhibitor with abiraterone acetate, an androgen biosynthesis inhibitor sold by the company under the brand name Zytiga.

The approval covers a combination regimen of Akeega with prednisone and is based on data from the Phase III MAGNITUDE study, a randomized, double-blinded and placebo-controlled trial with 765 participants. Compared with Zytiga plus prednisone, the Akeega-based regimen significantly improved radiographic progression-free survival by 47% in BRCA-positive patients.

Aug 10:

Janssen also won the FDA’s accelerated approval for its first-in-class bispecific T cell engager Talvey (talquetamab) as a treatment for relapsed or refractory multiple myeloma. By targeting both the CD3 and the GPRC5D proteins, Talvey works by bringing together T cells and myeloma cells, allowing the body’s immune system to exert its anti-cancer effects.

The accelerated approval was based on a Phase II study in which an overall response rate of 73.6% was seen in patients with at least four prior lines of therapy. Response was durable for a median of 9.5 months in the lower dosing group. Median duration of response was not yet reached in the higher dose arm. Like Pfizer’s Elrexfio, Talvey comes with a boxed warning for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.

Aug 9:

Nearly three years after first winning accelerated FDA approval of Gavreto (pralsetinib) in metastatic non-small cell lung cancer (NSCLC) with RET fusions, Genentech (Roche) and Blueprint Medicines announced the drug’s conversion to full approval.

RET fusions are present in just 1-2% of NSCLC cases, according to Genentech. The original FDA nod was based on an overall response rate (ORR) of 57% and median duration of response (DoR) that had not yet been reached in 114 patients in the Phase I/II ARROW study. The conversion to traditional approval was granted based on an additional 123 patients and 25 months of further follow-up. Treatment-naïve patients saw a median DoR of 13.4 months with a 78% ORR, while patients previously treated with platinum-based chemotherapy had an ORR of 63% and DoR of 38.8 months.

Aug 9:

Shares of Galera Therapeutics plummeted more than 80% Wednesday after the FDA rejected the company’s application for avasopasem manganese (avasopasem). The drug was being proposed to treat severe oral mucositis (SOM)—or mouth sores—resulting from radiotherapy in patients with head and neck cancer.

In its Complete Response Letter, FDA said results from the Phase III ROMAN trial, in combination with the GT-201 trial, were “not sufficiently persuasive to establish substantial evidence of avasopasem’s effectiveness and safety” in reducing these mouth sores. Galera will need to provide results from an additional clinical trial in order to resubmit the application, the Malvern, Penn–based company said in a press release. Impacts for the company’s workforce were swift, as Galera announced it would reduce its numbers by approximately 70% in order to extend its cash runway.

Aug 4:

In another milestone moment, the FDA approved Biogen and Sage Therapeutics’ zuranolone—henceforth Zurzuvae—as the first pill for postpartum depression (PPD). Zurzuvae is only the second treatment for this indication and the first pill that can be taken at home. The drug—a neuroactive steroid that works as a positive allosteric modulator of GABA-A receptors—also acts much more quickly than other approved depression treatments, with improved symptoms seen in trials in as few as three days.

Despite the significance of the approval, Sage and Biogen had sought a much larger slice of the depression market, but this will have to wait as the FDA rejected zuranolone for the treatment of major depressive disorder (MDD). In its Complete Response Letter, the FDA stated that the application did not provide “substantial evidence of effectiveness” to support its approval and that further research would be required. On a conference call following the decision, Sage CEO Barry Greene said only that the companies are “reviewing the feedback and evaluating next steps.”

Aug 4:

Mesoblast will have to provide more data before the FDA may approve its BLA for remestemcel-L for the treatment of pediatric steroid-refractory acute graft versus host disease (SR-aGVHD). In response to the FDA’s complete response letter (CRL), announced Friday by Mesoblast, the New York–based biopharma will “conduct a targeted, controlled study in the highest-risk adults with the greatest mortality.” Mesoblast noted that the adult study is in line with its overall commercial strategy, which involves a progression from pediatric to adult SR-aGVHD indications. This is the second rejection for remestemcel-L, after the FDA first turned down Mesoblast’s application in 2020, despite a 9-1 advisory committee vote in its favor.

Aug 3:

In 2019, the FDA approved the first vaccine for Ebola, a deadly viral hemorrhagic fever, for adults 18 years and older. Now, that vaccine—Ervebo, developed by Merck—is available to children 12 months and older. The FDA’s decision follows a recommendation on July 20 by the European Medicines Agency's Committee for Medicinal Products for Human Use to expand Ervebo’s label to children one year and older. The vaccine is only FDA-approved to protect against the Zaire ebolavirus and not other species of Ebola or Marburgvirus and the duration of protection is unknown, according to Merck.

Aug 2:

Taiho Oncology picked up a label expansion for its cancer drug Lonsurf (tipiracil), alone or as part of a combination regimen with Roche’s Avastin (bevacizumab) in metastatic colorectal cancer (mCRC). The nod came nearly eight years after Lonsurf first won approval as a monotherapy for mCRC in Sept. 2015. The expansion pertains to patients who had previously been treated with an anti-VEGF biologic agent and fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. Patients whose cancer has the wild-type RAS protein and who have previously received an anti-EGFR therapy are also eligible for the new combination.

The FDA’s decision was supported by the Phase III SUNLIGHT trial, where the Lonsurf–Avastin combination led to a median overall survival of 10.8 months versus 7.5 months on Lonsurf monotherapy, for a 39% reduction in risk of death.


July 31:

GSK’s Jemperli (dostarlimab-gxly) won FDA approval as a frontline treatment for primary advanced or recurrent endometrial cancer. The regulatory nod is the first new frontline treatment for patients whose cancer is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) in decades, according to GSK. Jemperli is also the first immuno-oncology treatment and PD-1 inhibitor to be authorized for frontline use in this patient population.

Jemperli, an anti-PD-1 antibody, was first approved in April 2021 for recurrent or advanced dMMR endometrial cancer. The FDA accepted the supplemental BLA to move the drug into the frontline setting on June 6 and set a target action date of Sept. 23, meaning Monday’s approval came nearly two months ahead of schedule.

July 29:

Citius Pharmaceuticals’ plans to bring a reformulated version of Eisai’s withdrawn cancer drug Ontak were put on hold on Saturday after the FDA rejected its BLA for Lymphir (denileukin diftitox). Citius acquired the drug from Dr. Reddy's Laboratories in Sept. 2021.

An engineered IL-2-diphtheria toxin fusion protein being developed to treat relapsed or refractory cutaneous T-cell lymphoma (CTCL), Lymphir specifically binds to IL-2 receptors to precisely deliver its toxic payload, thereby preventing protein synthesis in malignant T cells. The drug also targets the immunosuppressive regulatory T cells, which allows the body to mount a stronger immune response against the cancer.

In its announcement of the Complete Response Letter, Citius said the FDA will require it to “incorporate enhanced product testing and additional controls” into the BLA. No clinical efficacy or safety issues were raised and Citius stated it will continue working toward FDA approval of Lymphir.  

July 28:

The FDA approved RiVive, a 3 milligram (mg) naloxone hydrochloride nasal spray manufactured by Harm Reduction Therapeutics, as the second over-the-counter (OTC) naloxone rescue option for opioid overdose. The approval comes just four months after the regulator greenlit Narcan, a 4-mg naloxone hydrochloride nasal spray, as the first OTC naloxone product. Narcan is manufactured by Emergent BioSolutions. Naloxone rapidly reverses the effects of opioid overdose—a long-running epidemic that claimed the lives of more than 105,000 people in the U.S. in the year ending in February 2023, according to the FDA.

In a press release announcing RiVive’s approval, FDA Commissioner Robert Califf stated the regulator’s commitment to making naloxone accessible and encouraged other manufacturers of these products to discuss potential nonprescription development programs with the FDA.

July 26:

Octapharma secured approval for Balfaxar (prothrombin complex concentrate) for the reversal of the blood-thinner Warfarin in emergency surgery and invasive procedures. Warfarin increases the risk of bleeding—a serious complication during surgery. Balfaxar works to quickly increase blood levels of key clotting factors and antithrombotic proteins. A lyophilized powder, it is reconstituted in a device developed by Octapharma.

While Balfaxar met the primary endpoint of hemostatic efficacy in a Phase III study and was non-inferior to the comparator, Kcentra, fatal and non-fatal arterial and venous thromboembolic complications were observed in clinical trials and post-marketing studies, and healthcare providers are advised to monitor patients for signs of thromboembolic events.

The approval is the third for Balfaxar, which is already marketed in Canada and the EU as octaplex.

July 25:

People with an eyelid disease called demodex blepharitis now have a treatment option as the FDA approved Tarsus Pharmaceuticals’ Xdemvy. A prescription eyedrop, Xdemvy aims to eradicate the root cause of the disease—demodex mites that burrow in the eyelash follicles of sufferers. Xdemvy is the first therapy approved for the condition. 

Approval for Xdemvy was granted based on two randomized, multicenter, double-masked, vehicle-controlled studies of 833 patients, in which 415 patients received the treatment. A significant improvement was seen in each study by day 43, Tarsus stated in its approval announcement, adding that the therapy was “generally safe and well-tolerated.” 

Tarsus will have a significant market for Xdemvy as demodex blepharitis affects around 25 million people in the U.S. and accounts for more than two-thirds of all blepharitis cases, according to Tarsus. 

July 24:

The FDA has approved the first treatment for adults and children two years and older with molluscum contagiosum, a viral skin infection that affects around 6 million people in the U.S. every year.  A topical solution developed by Verrica Pharmaceuticals, YCANTH is a drug-device combination that contains a GMP-controlled formulation of cantharidin, a substance derived from the blister beetle Cantharis vesicatoria. It works by causing a blister to form on the wart or growth, eventually lifting it off the skin. 

YCANTH’s approval is based on data from two randomized, double-blind, multicenter Phase III trials. In each trial, a clinically and statistically significant number of patients treated with YCANTH achieved complete clearance of all treatable molluscum lesions, meeting the primary endpoint. No serious adverse reactions were reported in either trial. The company expects to make YCANTH available to patients and caregivers by September, Ted White, Verrica’s president and CEO, said in a statement.

July 20:

Four years after it was rejected by the FDA due to safety concerns, Daiichi Sankyo’s Vanflyta (quizartinib) won approval to treat patients with acute myeloid leukemia that has a FLT3-ITD gene mutation. In 2019, an FDA advisory committee voted that the benefit conferred by quizartinib did not outweigh the safety risks. Thursday’s approval comes with a Boxed Warning for three heart disorders: QT prolongation, torsades de pointes and cardiac arrest, and will only be available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program.

Daiichi Sankyo supported its NDA, accepted last Fall, with data from a Phase III trial that showed the quizartinib regimen—combined with standard induction and consolidation chemotherapy and continued as a single agent)—reduced the risk of death by 22.4% compared to patients on chemotherapy alone. After 39.2 months of follow-up, quizartinib more than doubled the overall survival advantage, the company stated in a press release.

July 20:

Emergent BioSolutions secured approval for Cyfendus, a vaccine intended for use after exposure to bacillus anthracis, a bacterium that causes anthrax. Cyfendus is required to be used in combination with “recommended” antibacterial drugs, according to Emergent’s announcement. The approval was based on a series of studies, including a pivotal Phase III trial assessing the vaccine’s consistency, immunogenicity and safety in healthy adults. Even before the approval, Emergent had been supplying Cyfendus to the U.S. Department of Health and Human Services under pre-Emergency Use Authorization for four years. 

July 17:

Infants and children at severe risk of RSV have another treatment option after the FDA approved Sanofi and AstraZeneca’s Beyfortus (nirsevimab). A monoclonal antibody, Beyfortus is just the second RSV drug authorized in the U.S. for high-risk children, the other being Synagis (palivizumab), which was approved in 1998. The companies’ bid for approval was backed by three late-stage trials that demonstrated the antibody’s safety and efficacy. Beyfortus will be available in the U.S. ahead of the 2023/2024 RSV season for children entering their first RSV season and those at severe risk up to 24 months, Sanofi stated in a press release.

July 13:

The FDA approved Perrigo Company’s Opill (norgestrel)—a progestin-only daily oral contraceptive—as the first-ever birth control pill available over the counter in the U.S. Perrigo expects Opill to be available online and in-person at drug stores, convenience stores and grocery stores in the first quarter of 2024. In a prepared statement, Perrigo President and CEO Patrick Lockwood-Taylor said the approval “marks a truly momentous day for women's health nationwide.” 

July 6:

A short workweek in the U.S. ended with big news as the FDA granted traditional approval to the first anti-amyloid antibody—and the first disease-altering drug—for Alzheimer’s disease. The accelerated approval for Eisai and Biogen’s Leqembi (lecanemab) was converted to a full approval based on results from the confirmatory Clarity-AD trial, which the FDA said in its statement verified the drug’s benefit. With the approval, Medicare coverage for Leqembi is expected to begin right away, with the requirement of a patient registry intended to collect further information on the effectiveness of this drug class in Alzheimer’s. 

July 3:

Amneal Pharmaceuticals received a Complete Response Letter for IPX203—a novel oral formulation of carbidopa/levodopa (CD/LD), a well-established combination for the management of Parkinson’s disease. In its rejection letter, the FDA said that while Amneal was able to adequately establish the safety of levodopa, it was not able to sufficiently do so for carbidopa. The regulator has requested additional pharmacokinetic data. The New Jersey–based company stated it plans to meet with the FDA to determine the best path forward for the treatment.


June 29:

Capping a busy week, the FDA approved BioMarin’s Roctavian (valoctocogene roxaparvovec-rvox) as the first gene therapy for adults with severe hemophilia A. Hemophilia is a rare genetic bleeding disorder caused by a mutation in the gene that encodes factor VIII (FVIII), which is necessary for blood to clot. A one-time gene therapy, Roctavian contains a healthy gene for factor VIII. Delivered through an adeno-associated virus (AAV) vector, the gene is expressed in the liver to increase blood levels of FVIII, thereby reducing the risk of uncontrolled bleeding. 

June 28:

The FDA notched another milestone with the approval of the first cellular therapy for type 1 diabetes. Lantidra (donislecel) developed by Chicago-based CellTrans, is a cell therapy made from the pancreatic islet cells of deceased donors. It is intended for adult patients whose repeated hypoglycemic episodes leave them unable to hit average blood glucose levels. In a clinical trial of 30 patients, 21 were insulin-free for at least a year; 11 didn’t require insulin for between one and five years and 10 were insulin-free for more than five years. Five patients failed to achieve any days of insulin independence.

June 28:

Pfizer’s bet on OPKO Health’s human growth hormone analog paid off as the FDA approved the treatment—which will be marketed as Ngenla—to treat children whose production of growth hormones is impaired. Pfizer purchased exclusive global commercialization rights for the then-experimental treatment in December 2014 for $295 million upfront and a promise of up to $275 million in milestones. This was the partners’ second try for FDA approval after the regulator rejected Ngenla’s first bid in January 2022. Pfizer and OPKO did not state the reasons for the initial denial.

June 28:

The FDA declined to approve Eton Pharmaceuticals’dehydrated alcohol injection for the treatment of methanol poisoning, citing concerns related “primarily to Chemistry Manufacturing and Controls.” This is the second Complete Response Letter issued to Eton for this proposed treatment. In the first, issued in March 2021, the FDA indicated that travel restrictions due to the COVID-19 pandemic prevented a timely inspection of the company’s European contract manufacturing site.

June 27:

The FDA approved UCB’s Rystiggo (rozanolixizumab), a subcutaneously administered humanized IgG4 monoclonal antibody, to treat generalized myasthenia gravis, a rare muscle-wasting autoimmune disease. Rystiggo is the only treatment approved to treat patients who are anti-acetylcholine receptor- or anti-muscle-specific tyrosine kinase antibody-positive. The regulatory green light was based on a Phase III trial that showed Rystiggo led to significant improvements in symptoms related to breathing, talking, swallowing and rising from a chair.

June 23:

The FDA greenlit Pfizer’s Litfulo (ritlecitinib) for the treatment of patients as young as 12 years with severe alopecia areata, an autoimmune disease characterized by patchy or complete hair loss on the scalp, face or body. Litfulo inhibits Janus kinase 3 and the tyrosine kinase and is believed to work by blocking the signaling of cytokines and cytolytic activity of T cells, which are implicated in alopecia areata.

June 22

In one of the year’s most-anticipated regulatory decisions, the FDA approved Sarepta’s Elevidys—formerly SRP-9001—for children 4 to 5 years with Duchenne muscular dystrophy. Elevidys is the first-ever gene therapy for DMD, a neuromuscular disease characterized by progressive muscle weakness and atrophy that strikes primarily young boys. The gene therapy was approved via the FDA’s accelerated approval pathway based on data that established it increased the expression of the Elevidys micro-dystrophin protein.

June 21:

Eli Lilly and Boehringer Ingleheim’s Jardiance (empagliflozin) and Synjardy (empagliflozin and metformin hydrochloride) picked up another indication, becoming the first and only SGLT2 inhibitors approved for children 10 years and older with type 2 diabetes. Previously, there had only been one oral drug for this indication: metformin, which was approved in 2000.

June 20:

Argenx will bring to market the first subcutaneous injectable for generalized myasthenia gravis (gMG), a rare muscle-wasting autoimmune disease. Vyvgart (efgartigimod) was first approved in 2021 as a one-hour intravenous infusion. Vyvgart is an antibody fragment that binds to the neonatal Fc receptor to prevent recycling of immunoglobulin G back into the blood. This includes a reduction in abnormal AChR antibodies, which are present in approximately 85% of gMG patients. AChR antibodies block the acetylcholine receptors from being able to receive signals from the nerve to stimulate a muscular response. Their normalization should ostensibly improve muscular function.

Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter @chicat08.

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