When Covid-19 vaccines roll out for the fall and winter respiratory illness season, they will continue to be based on the same lineage that is the basis for vaccines from this past season, but tweaked to address the variant that is currently prevalent in the U.S. and some other parts of the world.
An advisory committee to the FDA last week voted to recommended monovalent vaccines based on the JN.1 lineage. The FDA does not have to follow committee votes, but it often does. In this case, the agency followed the committee, but with additional direction to vaccine manufacturers that their vaccines should “preferentially” use the LP.8.1 strain, a variant descended from JN.1. LP.8.1 is currently the most widely circulating variant in the U.S., according to Centers for Disease Control and Prevention data.
The FDA instructions on next season’s Covid-19 vaccines come as the agency changes its policy on who should get vaccinated. In an article published last week in the New England Journal of Medicine, FDA commissioner Martin Makary FDA Director of the Center for Biologics Evaluation and Research Vinay Prasad stated that going forward, the agency will emphasize vaccination for certain population groups, such as the elderly, who face a high risk for severe outcomes from Covid-19 infection. For younger and healthier people, the FDA said it will need to see data from randomized, controlled clinical trials before it approves biologic license applications.
The FDA signaled its change in thinking in its approval of Novavax’s Covid-19 vaccine. The regulatory decision announced last week permits the vaccine only for those age 65 and older as well as those age 12 through 64 who have at least one underlying condition that puts them at high risk for severe outcomes from a Covid-19 infection. That’s in contrast to the messenger RNA Covid-19 vaccines marketed by Pfizer and Moderna, which are approved for broader use.
The narrower approval of Novavax’s vaccine is consistent with discussion last month by the CDC’s Advisory Committee on Immunization Practices (ACIP). During the April meeting of ACIP, committee members discussed changing its recommendation to focus on high-risk groups. In the NEJM article, Makary and Prasad said the benefit of repeat dosing, particularly in low-risk individuals, is uncertain. The FDA will be looking for that evidence.
“The FDA will approve vaccines for high-risk persons and, at the same time, demand robust, gold-standard data on persons at low risk,” Makary and Prasad wrote. “These clinical trials will inform future directions for the FDA, but more important, they will provide information that is desperately craved by health care providers and the American people.
There’s plenty of other news from the FDA. Here’s a recap of recent regulatory developments:
Regulatory Decisions
—Liquidia received a long-awaited FDA approval for Yutrepia, a treatment for pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. The drug is formulated as an inhalable powder administered by a palm-sized device. The active ingredient in Yutrepia is treprostinil, a now generic drug. The new Liquidia drug will compete with a franchise of treprostinil products marketed by United Therapeutics.
—Blockbuster GSK biologic drug Nucala added chronic obstructive pulmonary disease to its label, its fourth indication. The drug treats type 2 inflammation associated with COPD. In this indication, it compete with the type 2 inflammation-fighting Sanofi drug Dupixent.
—A Fujirebio Diagnostic is now the first FDA-cleared blood-based test for Alzheimer’s disease. The diagnostic tests for levels of two proteins, which correlates with the presence or absence of amyloid plaques in the brain that are characteristic of the neurodegenerative disorder. Fujirebio already markets an Alzheimer’s diagnostic that tests for these proteins in cerebrospinal fluid, which requires an invasive spinal tap to procure a sample.
—Merck drug Welireg expanded its approval to include the treatment of adults and children age 12 and older who have advanced cases of pheochromocytoma or paraganglioma (PPGL), two rare types of tumors. The regulatory decision makes Welireg the only FDA-approved treatment in the U.S. for PPGL. Welireg won its initial approval in 2021 as a treatment for von Hippel-Lindau disease, a rare inherited disorder that causes benign tumors that may become cancerous. Merck reported $509 million in Welireg sales in 2024, up from $218 million in the prior year.
—Incyte drug retifanlimab landed a long-awaited approval, alongside chemotherapy, as a first-line treatment for advanced cases of squamous cell carcinoma of the anal canal. The regulatory decision also covers use of the drug as a single agent for this type of cancer for those whose disease progresses on chemotherapy or if they are intolerant of it. The FDA rejected the antibody drug in this indication in 2021, asking the company for more data. Retifanlimab, brand name Zynyz, won its first FDA approval in 2023 as a treatment for metastatic Merkel cell carcinoma. Zynyz accounted for $3.2 million in revenue in last year, according to Incyte’s annual report.
—AbbVie’s Emrelis received accelerated FDA approval for the treatment of non-small cell cancer characterized by overexpression of a protein called c-Met. The drug is an antibody drug conjugate designed to target that protein. AbbVie said Emrelis represents its first internally developed solid tumor medicine as well as it first solid tumor FDA approval in lung cancer.
—A combination therapy from Verastem Oncology is now the first FDA-approved treatment for low-grade serous ovarian cancer (LGSOC), a rare type of ovarian cancer. The therapy pairs two oral small molecules, each with different dosing schedules. The combination treatment will be marketed as Avmapki Fakzynja Co-Pack.
—The European Commission granted marketing authorization to Eisai Alzheimer’s disease drug, Leqembi, but in a more limited patient population compared its approved use in the U.S. Patients who carry the ApoE4 gene face a greater risk of developing Alzheimer’s and they also face a greater risk of experiencing complications from Leqembi. The risks are greater for carriers of two copies of the gene. The commission approved Leqembi only for patients who have one or no copies of ApoE4.
—Johnson & Johnson drug Imaavy received FDA approval for treating the rare neuromuscular disorder generalized myasthenia gravis, but with a broader label compared to rival products from Argenx and UCB for this indication. It’s the first approval for Imaavy, which J&J projects could achieve $5 billion in peak sales across multiple immunological disorders. Imaavy came from J&J’s $6.5 billion acquisition of Momenta Pharmaceuticals.
—Akeso won FDA approval for penpulimab, in combination with standard chemotherapies, as a first-line treatment for recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC) in adults. The agency also approved the Hong Kong-based biotech’s drug as a single-agent treatment for adults with metastatic non-keratinizing NPC that has progressed on or after chemo. Penpulimab, an antibody designed to block the checkpoint protein PD-1, is Akeso’s first internally developed drug to receive FDA approval.
—The European Commission approved AstraZeneca’s Calquence, alongside standard-of-care chemotherapy, as a first-line treatment for mantle cell lymphoma (MCL). The oral small molecule is an inhibitor of BTK, an enzyme that supports cancer growth. The FDA approved Calquence as a first-line MCL treatment in January. The twice-daily pill was initially approved in 2017 as a second-line MCL treatment.
—The FDA lifted its clinical hold on Atara Biotherapeutics immunotherapy Ebvallo, a potential treatment for advanced Epstein Barr virus positive post-transplant lymphoproliferative disease (EBV+LPV). The FDA placed a hold on the drug in January, just days after rejecting the therapy due to issues at a third-party manufacturer. Ebvallo, an off-the-shelf therapy made by bioengineering T cells harvested from healthy donors, won its European approval in EBV+LPV in 2022.
—Abeona Therapeutics’ Zevaskyn, a cellular gene therapy made from a patient’s own skin cells, received FDA approval for the treatment of recessive dystrophic epidermolysis bullosa, an inherited disorder in which the lack of a key protein needed to hold the layers of skin together makes patients susceptible to wounds and blisters. Zevaskyn is the third FDA-approved treatment for epidermolysis bullosa in the past two years, joining Krystal Biotech’s Vyjuvek and Chiesi Group’s Filsuvez.
—Blockbuster Sanofi and Regeneron Pharmaceuticals drug Dupixent received FDA approval for its seventh indication: chronic spontaneous urticaria. The FDA turned down Sanofi’s Dupixent application in this indication in 2023. The latest regulatory decision for the product is based on a resubmission that included data from another Phase 3 study.
—Click Therapeutics mobile app CT-132 received FDA marketing authorization as a treatment for prevention of episodic migraine. The software joins a Click digital therapeutics portfolio that includes commercialized apps for smoking cessation, major depressive disorder, and type 2 diabetes.
Stumbles and Setbacks
—The FDA extended the regulatory decision target date for Biohaven’s troriluzole in spinocerebellar ataxia, a rare neurodegenerative disorder with no approved treatments. Biohaven was expecting a decision in the third quarter of this year, but the biotech said the FDA extended the review by three months to allow time to review additional information it had asked the company to submit. The FDA also said it plans to convene an advisory committee to discuss troriluzole.
Troriluzole has a history of clinical trial and regulatory setbacks, including a 2023 refuse to file letter. But discussions with the FDA led to a new clinical trial protocol that incorporated real-world data. The regulatory submission is based on positive results from that study reported last year.
—Valneva’s chikungunya vaccine faces greater regulatory scrutiny due to postmarketing reports of serious adverse events, including neurological and cardiovascular complications, in older adults. The FDA and Centers for Disease Control and Prevention recommended a pause in dosing of the vaccine, Ixchiq, in adults age 60 and older. Separately, the European Medicines Agency opened its own inquiry and said that for now, the vaccine must not be used in adults age 65 and older. Valneva said it has “engaged proactively” with health authorities in all regions where Ixchiq is available.
—Cytokinetics must wait longer for an FDA decision on its obstructive hypertrophic cardiomyopathy drug candidate, aficamten. The agency asked the biotech to submit a Risk Evaluation and Mitigation Strategy that was not included in the original submission. This major amendment to the application extends the drug’s review by three months; the new target date for a regulatory decision is Dec. 26.
—Stealth BioTherapeutics also faces a delay. The FDA missed the April 29 target date for a decision on elamipretide, a drug that could potentially become the first approved treatment for Barth syndrome, an ultra-rare mitochondrial disorder. The FDA did not give Stealth a new target date for a decision. Here’s more on elamipretide and its long development and regulatory path.
—The FDA placed a clinical hold on Phase 1b testing of Vyne Therapeutics’ VYN202, an experimental treatment for moderate-to-severe plaque psoriasis. Bridgewater, New Jersey-based Vyne said the hold follows a recent observation of testicular toxicity in dogs from a non-clinical toxicology study. Screening, enrollment, and dosing have been suspended in humans. Vyne said that no serious adverse events have been reported in the clinical trial.
More Changes at FDA
—The FDA is rolling out the use of artificial intelligence internally across all of the agency’s centers, with a goal of completing this integration by the end of June. The move follows completion of a new generative AI pilot for scientific reviewers. According to the FDA, these generative AI tools will allow staff to spend less time on tedious, repetitive tasks that often slow down the review process. AI is also a key component of the FDA’s plans to phase out animal testing requirements for drug submissions. The transition includes accepting data that companies generate with computational techniques and AI to predict drug behavior and side effects in humans.
Illustration: appledesign, Getty Images
