FDA Action Alert: Merck, BMS, Sarepta and more

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace

With six upcoming action dates, the FDA has a very busy week ahead. The agency is expected to announce decisions on the drug applications for a pneumococcal vaccine, a gene therapy for Duchenne muscular dystrophy and an approval expansion for a key cancer treatment.

Read below to learn more.

Merck awaits verdict on pneumococcal vaccination

Merck is seeking approval of its 21-valent vaccine V116 to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults. The FDA is expected to announce its decision on June 17.

The pharmaceutical company is supporting its approval submission with data from the Phase III STRIDE-3 trial, which showed in November 2023 that V116 elicited non-inferior immune responses compared to a 20-valent comparator vaccine. Merck is also supporting the approval submission for V116 with several other trials, including STRIDE-3, STRIDE-4, STRIDE-5 and STRIDE-6. Data from additional trials will be presented at future medical conferences.

If approved, Merck’s vaccine would be the first pneumococcal conjugate vaccine specifically developed for use in adults.

Argenx files for approval for Vyvgart Hytrulo in CIDP

Argenx proposes 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 is expected to make its decision on June 21.

The Netherlands-based biotech company is supporting its supplemental biologics license application (sBLA) with data from the Phase II ADHERE trial, which showed a 61% reduction in the risk of relapse after treatment with Vyvgart Hytrulo compared to placebo. In the open-label phase of ADHERE, 67% of patients showed signs of clinical improvement.

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

BMS aims to expand Krazati into CRC

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 agency’s deadline for a decision is June 21.

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

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

Harmony aims to expand Wakix into pediatric narcolepsy

Harmony Biosciences proposes its oral drug Wakix (pitolisant) as a treatment for excessive daytime sleepiness in pediatric narcolepsy patients ages 6 and older. The FDA deadline for a decision is June 21.

In its sNDA, Harmony submitted data from a multicenter, randomized, placebo-controlled Phase III trial evaluating the efficacy and safety of Wakix in patients with narcolepsy ages six to 17, with or without cataplexy. The FDA granted the application Priority Review status.

Wakix is ​​an orally available histamine-3 receptor antagonist. It was approved by the FDA in August 2019 to treat excessive daytime sleepiness associated with narcolepsy in adults.

Merck aims to expand the growing list of Keytruda indications

By June 21, the FDA is expected to issue its ruling on Merck’s sBLA, which proposes using the blockbuster PD-1 inhibitor Keytruda in combination with standard chemotherapy to treat primary advanced or recurrent endometrial cancer.

Merck supports its offer for the additional indication with results from the Phase III NRG-GY018 study, which showed that the Keytruda-based regimen reduced the risk of disease progression or death by 46% in patients with successful mismatch repair. In patients with disease with inadequate mismatch repair, the risk of disease progression or death was reduced by 70% compared to chemotherapy alone.

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

Sarepta aims for full approval of its DMD gene therapy despite shaky data

In February 2024, the FDA accepted an efficacy supplement to Sarepta Therapeutics’ sBLA to convert the accelerated approval of gene therapy Elevidys (delandistrogens moxeparvovec-rokl) to a traditional approval and expand the approval to all patients with Duchenne muscular dystrophy (DMD) with confirmed DMD gene mutations. The FDA’s decision is expected on June 21.

Currently, Elevidys is only approved for ambulatory children ages 4 to 5. The FDA granted Elevidys accelerated approval in June 2023, a decision that has recently come under criticism, particularly because the gene therapy failed to meet its primary efficacy endpoint in Part 1 of the SRP-9001-102 trial and was unable to significantly outperform a placebo in terms of patients’ functional performance.

Sarepta’s push for full approval is supported by the Phase III EMBARK trial, which also missed its primary endpoint in October 2023. In patients treated with Elevidys, North Star Ambulatory Assessment Tool scores were only 0.65 points higher than placebo competitors after 52 weeks, an effect that did not reach statistical significance.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Contact him on LinkedIn or email him at [email protected] or [email protected].