Arguably the most notable of the FDA’s upcoming decisions is that regarding Gilead’s twice-yearly HIV prophylaxis lenacapavir.
Despite some high-profile recent delays, work continues for the FDA, which is due in the next two weeks to release important decisions on a handful of drug applications, including one for a rare genetic disease and two for RSV immunization.
Read below for more.
Merck Steps Up to RSV Starting Line With Clesrovimab
Merck is proposing its long-acting antibody clesrovimab to induce immunity against respiratory syncytial virus (RSV) infection in infants. The FDA is reviewing Merck’s application and is expected to release its decision by June 10.
Clesrovimab is backed by data from the Phase IIb/III CLEVER study, a pivotal, double-blind and placebo-controlled study that enrolled more than 3,600 infants up to 1 year of age who were entering their first RSV season. Results published in October 2024 showed that a single dose of clesrovimab could cut RSV-associated medically attended lower respiratory infection by 60.4% at 150 days versus placebo.
At this same time point, clesrovimab lowered RSV-associated hospitalizations by 84.2% and hospitalizations linked to lower respiratory infections in RSV by 90.9%.
If approved, clesrovimab will go toe-to-toe with Sanofi and AstraZeneca’s Beyfortus, likewise a monoclonal antibody that can prevent RSV infection in infants up to 24 months of age. Beyfortus has a nearly 2-year head-start—it won the FDA’s approval in July 2023—and a wealth of evidence that Merck will need to surmount. In March 2024, for instance, data from the U.S. Centers for Disease Control and Prevention showed that Beyfortus was 90% effective against RSV hospitalizations.
Moderna Seeks Broader Adult Label for RSV Vaccine
Also awaiting an RSV verdict is Moderna, which is trying to expand its RSV vaccine mRESVIA into high-risk adults aged 18 to 59 years. As per the company’s fourth-quarter and full-year 2024 business report, the FDA’s target decision date is June 12.
The FDA first cleared mRESVIA in May 2024, allowing its use in older adults aged 60 and up. By then, however, Moderna’s vaccine already had two powerhouse competitors in GSK’s Arexvy and Pfizer’s Abrysvo, both of which were given regulatory clearance in mid-2023—nearly a year ahead of mRESVIA—in the same target population. The head start has given both vaccines enough time to expand beyond seniors: Pfizer pushed Abrysvo into adults 18 through 59 years in October 2024, while GSK secured approval for at-risk people aged 50 through 59 in June of last year.
Just weeks after Arexvy’s expanded approval by the FDA, however, the CDC dealt the RSV space a blow, narrowing its vaccination guidelines to cover only seniors aged 75 and up, and those 60 through 74 years who are at risk of contracting severe disease.
Data backing mRESVIA’s expansion, presented during Moderna’s R&D day in September 2024, showed that the vaccine was safe and well-tolerated in this at-risk younger population and could match its immunogenicity profile in its currently approved population.
UroGen’s Bladder Cancer Drug Nears Decision Date After Losing AdComm Vote
By June 13, the FDA is expected to release its verdict on UroGen’s investigational cancer drug UGN-102, which the biotech is proposing for the treatment of low-grade, intermediate-risk non–muscle invasive bladder cancer.
UroGen is backing its approval bid with data from the Phase III ENVISION trial, a readout from which in December 2024 demonstrated “promising” long-term outcomes, according to the biotech. At three months, 76.9% of patients achieved a complete response. Duration of response at 12 months was 82.3% among complete responders.
Despite this encouraging profile, the FDA’s Oncologic Drugs Advisory Committee last month voted against recommending the approval of UGN-102. According to reporting from OncLive at the time, the panel was narrowly divided, with the vote ultimately coming in at 5–4 against UroGen. Among the issues cited by the outside experts were the lack of a completely randomized trial and the short follow-up.
KalVista Oral Angioedema Drug Awaits FDA Response
Massachusetts biotech KalVista is developing its oral plasma kallikrein inhibitor sebetralstat for the on-demand treatment of hereditary angioedema (HAE) in patients aged 12 and up. The FDA is currently reviewing the drug application and is set to release a decision on June 17.
Afflicting one in every 50,000 people, HAE is a rare genetic disorder characterized by frequent, painful and often debilitating tissue swelling across the body, which can become life-threatening in certain cases. The disease is caused by a deficiency or dysfunction in the C1 esterase inhibitor protein, which normally helps keep the kallikrein-kinin pathway in check. The kallikrein-kinin system, in turn, helps maintain healthy blood pressure, renal function and immunity.
Sebetralstat works by inhibiting kallikrein, assuming the role of the deficient C1 esterase inhibitor. KalVista is backing sebetralstat’s FDA bid with data from the Phase III KONFIDENT trial, which showed that both 300-mg and 600-mg doses of the drug achieved symptom relief significantly faster than placebo. Sebetralstat was also safe and well-tolerated, with an adverse event profile similar to that of placebo.
If approved, sebetralstat will become the first oral and on-demand HAE drug to lower the incidence of attacks in adult and pediatric patients 12 and above, according to a September 2024 release from KalVista.
Gilead Prepares for Twice-Yearly PrEP Approval
Arguably the most highly anticipated regulatory action on this list is the FDA’s decision for Gilead’s twice-yearly lenacapavir injection for pre-exposure prophylaxis (PrEP) for HIV. The FDA is scheduled to release its decision on June 19.
Anticipating an approval, Gilead has been preparing to launch the product, engaging in what Chief Commercial Officer Johanna Mercier called “market development initiatives” on an investor call in April. “We are absolutely ready for the launch,” she said, noting that partly because of Gilead’s efforts, the U.S. PrEP market has grown 16% year-on-year.
Writing to investors on Feb. 12, Jefferies analysts noted that the HIV community appeared to be “educated” and prepared for lenacapavir, with some observers “already seeing increases in HIV doc appointments scheduling” ahead of approval.
Gilead is backing lenacapavir’s application with data from the Phase III PURPOSE 1 and PURPOSE 2 studies. PURPOSE 1, which focused on cisgender women, demonstrated a 100% efficacy rate for preventing HIV infection. PURPOSE 2, meanwhile, enrolled a more diverse population of cisgender men, transgender men, transgender women and nonbinary individuals who have sex with partners assigned male at birth. Results showed that twice-yearly lenacapavir cut HIV incidence by 96%.
Sanofi, Regeneron Eye Expansion of Dupixent Into Bullous Pemphigoid
Sanofi and Regeneron are looking to add another indication to the label of their blockbuster biologic Dupixent, this time seeking approval in bullous pemphigoid. Their application is currently undergoing regulatory review, with a decision set for June 20.
Pivotal data backing the application showed that five times more patients on Dupixent achieved sustained disease remission versus placebo, being able to taper oral corticosteroids by week 16 and stay off such medication for at least 20 weeks. Dupixent likewise significantly improved disease severity and itch in patients with moderate-to-severe bullous pemphigoid.
If approved, Dupixent will become the first targeted therapy for bullous pemphigoid in the U.S., as per a February news release from Sanofi.
An approval would also continue Dupixent’s regulatory winning streak after the subcutaneous injection in September 2024 won clearance for chronic obstructive pulmonary disease—likewise making it the first biologic for this disease.
