FDA Action Alert: Merck, BMS, Sarepta and More

With six target action dates lined up, the FDA has a very busy week ahead. The regulator is expected to release decisions on drug applications for a pneumococcal vaccine, a gene therapy for Duchenne muscular dystrophy and a label expansion for one of cancer’s cornerstone therapies.

Read below for more.

Merck is seeking approval for its investigational 21-valent vaccine, dubbed V116, to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults. The FDA is expected to release its verdict on June 17.

The pharma is backing its regulatory bid with data from the Phase III STRIDE-3 trial, which in November 2023 showed that V116 induced non-inferior immune responses as compared with a 20-valent comparator vaccine. Merck is also supporting V116’s application with several other studies, including STRIDE-3, STRIDE-4, STRIDE-5 and STRIDE-6. Data from additional studies will be shared at future medical meetings.

If approved, Merck’s vaccine would become the first pneumococcal conjugate shot designed specifically for use in adults.

Argenx is proposing to use its antibody fragment Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) to treat the rare autoimmune disease chronic inflammatory demyelinating polyneuropathy (CIDP). The FDA’s decision is due on June 21.

The Netherlands-based biotech is supporting its supplemental Biologics License Application (sBLA) with data from the Phase II ADHERE study, which demonstrated a 61% reduction in the risk of relapse after treatment with Vyvgart Hytrulo versus placebo. In ADHERE’s open-label phase, 67% of patients showed evidence of clinical improvement.

Vyvgart Hytrulo is a subcutaneous formulation of the human IgG1 antibody fragment efgartigimod alfa, combined with the recombinant human hyaluronidase PH20, which allows its subcutaneous administration. The drug was approved in June 2023 for the treatment of generalized myasthenia gravis.

In February 2024, the FDA accepted Bristol Myers Squibb’s supplemental New Drug Application (sNDA) for its KRAS blocker Krazati (adagrasib), in combination with cetuximab, for the treatment of locally advanced or metastatic colorectal cancer (CRC). The deadline for the regulator’s decision is June 21.

The application, which seeks to make Krazati a treatment option for CRC patients with KRAS G12C-mutated CRC, is supported by data from the KRYSTAL-1 study. BMS reported data from this trial in March 2024, touting a 34% objective response rate at a median follow-up of 11.9 months. Median progression-free survival was 6.9 months, while median overall survival reached 15.9 months.

Krazati is an orally available small molecule inhibitor of G12C-mutated KRAS that won the FDA’s accelerated approval in December 2022. It was originally developed by Mirati Therapeutics, which BMS acquired in October 2023 for $4.8 billion.

Harmony Biosciences is proposing its oral drug Wakix (pitolisant) as a treatment for excessive daytime sleepiness in pediatric narcolepsy patients aged 6 years and above. The FDA’s deadline for a decision is June 21.

In its sNDA, Harmony provided data from a Phase III multicenter, randomized and placebo-controlled study evaluating the efficacy and safety of Wakix in narcolepsy patients ages six through 17 with or without cataplexy. The FDA granted the application its priority review status.

Wakix is an orally available histamine 3 receptor antagonist. It was approved by the FDA in August 2019 for the treatment of excessive daytime sleepiness of adult narcolepsy.

By June 21, the FDA is expected to release its verdict on Merck’s sBLA proposing to use its blockbuster PD-1 inhibitor Keytruda, in combination with standard of care chemotherapy, as a treatment for primary advanced or recurrent endometrial carcinoma.

Merck is supporting its bid for the additional indication with results from the Phase III NRG-GY018 study, which found that the Keytruda-based investigational regimen cut the risk of disease progression or death by 46% in patients whose disease was mismatch repair proficient. Meanwhile, those with mismatch repair deficient disease saw a 70% reduction in the risk of progression or death versus chemotherapy alone.

If approved, Keytruda would become the “first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” Gursel Aktan, vice president of global clinical development at Merck Research Laboratories, said in a statement accompanying the sBLA’s acceptance in February 2024.

In February 2024, the FDA accepted an efficacy supplement to Sarepta Therapeutics’ sBLA seeking to convert the accelerated approval of its gene therapy Elevidys (delandistrogene moxeparvovec-rokl) into traditional approval, as well as broaden its label to include all Duchenne muscular dystrophy (DMD) patients with confirmed DMD gene mutations. The FDA’s decision is due on June 21.

Currently, Elevidys is only indicated for ambulatory pediatric patients aged 4 through 5 years of age. The FDA granted Elevidys accelerated approval in June 2023, a decision that has recently come under fire, particularly as the gene therapy failed its primary efficacy endpoint in part 1 of the SRP-9001-102 study, unable to significantly outdo placebo in terms of patients’ functional performance.

Sarepta’s bid for full approval is supported by the Phase III EMBARK study, which in October 2023 also fell short of its primary endpoint. In patients treated with Elevidys, scores on the North Star Ambulatory Assessment tool at 52 weeks were only 0.65 points higher than placebo comparators, an effect that did not satisfy statistical significance.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.