FDA Action Alert: BMS, Merck, Sanofi/Regeneron and More

 

The FDA has six target action dates ahead to round out September as drugs for gastroparesis, Niemann-Pick disease type C and more await decisions.

The FDA has several big decision deadlines coming up, including two for blockbuster drugs seeking to push into new indications and one that could potentially open a new mechanism of treatment for schizophrenia.

Read below for more.

Vanda Proposes Tradipitant to Boost Stomach Emptying

By September 18, the FDA is expected to release its verdict on Vanda Pharmaceuticals’ new drug application (NDA) for tradipitant, an investigational NK-1R antagonist the Pennsylvania-based company is proposing for gastroparesis.

Afflicting around 6 million people in the U.S., gastroparesis is a serious condition that involves the delayed emptying of the stomach. As a result, patients with gastroparesis suffer from nausea, bloating, fullness after meals, vomiting and abdominal pain. Gastroparesis can also compromise social and occupational functioning. Many cases are undiagnosed.

Vanda’s answer to gastroparesis is tradipitant, a small molecule blocker of neurokinin (NK)-1 receptors, which are found in the gastrointestinal tract and in brain regions involved in the vomit reflex. NK-1 receptor antagonists are widely known as anti-emetics, giving tradipitant its potential to suppress the typical nausea and vomiting symptoms that come with gastroparesis.

Vanda’s data package for tradipitant includes clinical efficacy studies, data from a 12-week open-label study, evidence from an expanded-access program and non-animal preclinical toxicology data. The FDA previously placed tradipitant under a partial clinical hold, requiring Vanda to provide a standard, nine-month, non-rodent toxicity study before it could treat patients beyond 12 weeks.

Aside from gastroparesis, Vanda is also developing tradipitant for motion sickness and atopic dermatitis.

Zevra Awaits Verdict on Neimann-Pick Disease Type C Candidate

After clearing the FDA’s newly formed Genetic Metabolic Diseases Advisory Committee last month, Zevra Therapeutics is gearing up for the potential approval of its oral drug candidate arimoclomol for Niemann-Pick disease type C (NPC). The FDA’s deadline is September 21.

NPC is an ultrarare neurodegenerative lysosomal storage disease characterized by the progressive worsening of physical and cognitive function. The condition arises when mutations in the NPC1 and NPC2 genes impair the otherwise normal transport and clearance of cholesterol and other lipids from inside cells, resulting in the toxic buildup of these molecules in various organs, including the brain.

Patients with NPC often suffer from problems with speech, swallowing and movement. The disease is irreversible and can lead to death within months. There are currently no approved therapies for NPC.

Arimoclomol addresses NPC by crossing the blood-brain barrier to make nerves more resistant to destruction, even when under stress.

A panel of outside experts threw its support behind Zevra, voting 11–5 to recommend arimoclomol’s approval, though pointing out that the drug’s overall benefits seemed small.

Heron Awaits FDA’s Go-Ahead for Extended-Release Needle for Zynrelef

Heron Therapeutics is proposing a new extended-release solution vial access needle (VAN) for its local anesthetic Zynrelef (bupivacaine and meloxicam). The FDA is expected to release its verdict on or before September 23.

VAN is designed to “simplify” the preparation of Zynrelef, according to Heron’s news announcement. The new needle will also lower the withdrawal time for the drug to 20 to 45 seconds, down from the previous duration of up to three minutes. Heron calls VAN a “user-friendly” innovation that could also make Zynrelef safer to administer and increase its uptake.

If approved, VAN will replace the vented vial spikes currently deployed for Zynrelef and will be ready for roll-out in the fourth quarter of 2024, according to the biotech’s press release.

Zynrelef is a dual-acting local anesthetic that combines the nerve-blocking effects of bupivacaine and the anti-inflammatory activity of the nonsteroidal drug meloxicam. According to its label, Zynrelef was first approved in 2021 and is indicated for post-surgical pain relief after total knee arthroplasty, open inguinal herniorrhaphy and bunionectomy.

In Phase III studies, Zynrelef demonstrated significant pain reduction within the first 72 hours after surgery while also increasing the percentage of patients who did not require opioids. Zynrelef comes with a boxed warning for serious cardiovascular and gastrointestinal events, which could become fatal.

Merck Tries for Another Keytruda Indication: Pleural Mesothelioma

Merck is seeking to add pleural mesothelioma to the ever-growing label of its blockbuster PD-1 inhibitor Keytruda (pembrolizumab). The FDA’s decision is due September 25.

Pleural mesothelioma refers to malignancies originating in the membrane that lines the walls of the chest and the lungs. It is a rare malignancy most popularly linked with high exposures to asbestos, and case counts in the U.S. have dropped since the substance was banned in 2000, according to the Cleveland Clinic. Around 3,000 patients are diagnosed with mesothelioma each year, with 80% of cases occurring in the pleura.

Merck’s supplemental Biologics License Application (sBLA)—which the FDA accepted and granted Priority Review in May 2024—is backed by data from the pivotal Phase II/III KEYNOTE-483 study.

Results showed that Keytruda plus chemotherapy significantly improved overall survival (OS) in patients with unresectable advanced or metastatic malignant pleural mesothelioma, cutting the risk of death by 21% compared with chemotherapy alone. Progression-free survival was also significantly better in the Keytruda plus chemotherapy arm.

BMS Awaits Landmark Decision for Schizophrenia Drug KarXT

Arguably the FDA’s biggest decision this month is for Bristol Myers Squibb’s KarXT, an investigational muscarinic antipsychotic being proposed for the treatment of schizophrenia. The regulator’s decision is due September 26.

Unlike current treatments for schizophrenia, KarXT works via the dual activation of the M1 and M4 muscarinic receptors and does not directly block dopamine receptors. This unique mechanism of action allows KarXT to ease positive and negative cognitive symptoms in schizophrenia. If approved, KarXT would open up the first new pharmacological treatment approach to schizophrenia in many decades.

KarXT was originally developed by Karuna Therapeutics, which BMS acquired in December 2023 for $14 billion.

The FDA is currently reviewing BMS’ data package for KarXT, which includes findings from the EMERGENT clinical development program. EMERGENT-1 and EMERGENT-2, findings from which were released in 2021 and 2022, respectively, established the efficacy of KarXT in treating schizophrenia on the Positive and Negative Syndrome Scale (PANSS).

EMERGENT-3 then showed in March 2023 that KarXT could significantly improve overall symptom severity. However, this trial missed a key secondary endpoint and revealed potential cardiovascular risks, spooking investors.

In April 2024, BMS unveiled interim findings from the long-term, open-label EMERGENT-4 study, which validated KarXT’s efficacy in schizophrenia, showing that it elicited at least a 30% symptomatic improvement at 52 weeks in more than 75% of treated patients.

Sanofi, Regeneron Tee Up COPD Expansion for Dupixent

Following a delay in May 2024, the FDA is now nearing its deadline to decide on Sanofi and Regeneron’s bid to expand the label of their blockbuster treatment Dupixent (dupilumab) into chronic obstructive pulmonary disease (COPD). The regulator’s verdict is due September 27.

Dupixent is a fully human monoclonal antibody that targets and blocks the IL-4 and IL-13 pathways, in turn moderating the type 2 inflammatory response. This mechanism of action has won Dupixent several approvals in the space, including for atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyps. Dupixent is not immunosuppressive.

The pharma partners are backing Dupixent’s COPD bid with data from the Phase III BOREAS and NOTUS trials. In BOREAS, adding Dupixent to standard of care cut the rate of moderate or severe exacerbations by 30% over 52 weeks, while also boosting lung function and health-related quality of life. Meanwhile, recent data from NOTUS put Dupixent’s efficacy against moderate or severe exacerbations at 34%.

In May 2024, the FDA requested additional efficacy analyses from BOREAS and NOTUS. It noted, however, that the follow-up information would constitute a major amendment to Dupixent’s sBLA, thereby requiring a three-month extension to the review period. Sanofi and Regeneron at the time emphasized that the regulator raised no issues about the approvability of Dupixent in COPD.

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