Expected FDA Approvals in the Second Half of 2025

The drug industry closed 2024 with 50 new drug FDA approvals. The list includes Attruby (acoramidis), which treats transthyretin amyloid cardiomyopathy (a rare, genetic, potentially fatal heart condition), and Cobenfy (xanomeline-trospium), an antipsychotic with a novel mechanism of action.

Sixteen new drugs have passed muster with the FDA this year as of June 24. Among them are Vertex’s Journavx (suzetrigine), a first-in-class, nonopioid drug for acute pain, and Johnson & Johnson’s Imaavy (nipocalimab), which addresses the dearth of available therapies for muscle-specific tyrosine kinase antibody-positive myasthenia gravis.

The second half of the year promises more new drugs and treatments. Here are a few to keep an eye on.

Rilzabrutinib for thrombocytopenia

Paris-based Sanofi has two investigational Bruton tyrosine kinase (BTK) inhibitors moving through the pipeline for two indications. The first is rilzabrutinib, an oral, reversible, covalent BTK inhibitor being developed to treat persistent or chronic immune thrombocytopenia (ITP) in adults. ITP is a rare immune-mediated blood disorder in which the immune system attacks platelets, leading to an increased risk of bleeding.

In the pivotal LUNA 3 phase 3 trial, two-thirds of adults with persistent or chronic ITP receiving rilzabrutinib achieved platelet response compared with one-third ofthe patients taking placebo. The study met its primary end point of sustained platelet response in 23% of participants taking rilzabrutinib compared with none of those randomly assigned to take the placebo. Relative to the placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52%, reduced bleeding and improved fatigue and other measures of quality of life. Based on the positive trial results, Sanofi filed a new drug application, and the FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of August 29, 2025.

Aficamten for cardiomyopathy

Aficamten is an investigational oral, selective myosin inhibitor being developed by biopharmaceutical company Cytokinetics, Inc., to treat obstructive hypertrophic cardiomyopathy (HCM). With HCM, the cardiac muscle becomes abnormally thick, which leads to narrowing and stiffening of the interior left ventricle, the heart’s main pumping chamber. As a result, it is more difficult for the ventricle to relax and fill with blood, limiting the heart’s pumping capability. Symptoms include chest pain, shortness of breath, dizziness or fainting during physical activity. HCM is one of the leading causes of sudden cardiac death in young people and athletes.

Aficamten is designed to reduce heart muscle contraction by binding directly to cardiac myosin, a protein that regulates heart contractions. Cytokinetics filed a new drug application for aficamten based on results from the pivotal SEQUOIA-HCM phase 3 trial. The study randomly assigned 282 participants to receive aficamten or a placebo for 24 weeks. Results showed that aficamten significantly improved exercise capacity compared with placebo. Additional analyses also showed that the investigational molecule was associated with cardiac remodeling and improvements in heart structure and function. A PDUFA target action date is set for September 26, 2025.

Tolebrutinib
for multiple sclerosis

Sanofi’s second BTK inhibitor is tolebrutinib, an oral brain penetrant being developed for relapsing forms of multiple sclerosis (MS) and nonrelapsing secondary progressive MS (nrSPMS). The company obtained the investigational drug in 2020 after a $3.7 billion buyout of Principia Biopharma. Despite the setback of an FDA-imposed partial clinical hold in 2022 due to liver toxicity issues, tolebrutinib has emerged as a leading candidate for treating nrSPMS, for which there is no treatment.

Tolebrutinib is designed to penetrate the central nervous system and target the smoldering neuroinflammation characteristic of nrSPMS. Patients living with this form of MS stop experiencing disease relapses but become increasingly disabled.

The phase 3 HERCULES trial met its primary end point, demonstrating that tolebrutinib delayed disability progression by 31% compared with placebo in adults with nrSPMS. Based on these results, the company filed for FDA approval of tolebrutinib for the potential treatment of nrSPMS and to slow disability accumulation independent of relapse activity in adults. The agency set a PDUFA action date of September 28, 2025.

Depemokimab for severe asthma and nasal polyps

GSK, headquartered in London, is developing depemokimab, an investigational ultra-long-acting monoclonal antibody targeting interleukin-5 (IL-5). The cytokine IL-5 plays a key role in the pathology of type 2 inflammatory conditions, including severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP).

People with severe asthma have symptoms that do not respond to inhaled corticosteroids. They are prone to exacerbations, which negatively affect quality of life and contribute to the burden on healthcare resources. About 30% of people in the U.S. with chronic sinusitis have nasal polyps. The soft tissue growths are associated with chronic inflammation and may cause symptoms such as loss of smell, nasal obstruction and
sinus infections.

GSK is seeking FDA approval of depemokimab as adjunctive maintenance therapy for severe asthma with high eosinophil count in adults and children 12 years or older and as add-on maintenance treatment of CRSwNP in adults. The application is based on positive results from the SWIFT and ANCHOR phase 3 trials.

SWIFT-1 and SWIFT-2 evaluated the safety and efficacy of depemokimab as an add-on therapy in participants with severe asthma with type 2 inflammation. In each study, participants were randomly assigned to receive depemokimab injections or a placebo at weeks 0 and 26 in addition to their standard of care. Both studies met the primary end point of significant reduction in exacerbation and hospitalization rates at week 52. ANCHOR-1 and ANCHOR-2 assessed the safety and efficacy of depemokimab as adjunct therapy in adults with CRSwNP.

The primary end points for both trials were the change from baseline in total endoscopic nasal polyps score at week 52 and mean nasal obstruction score over weeks 49 through 52. Both trials met
those end points.

The PDUFA action date for depemokimab is December 16, 2025. If the FDA approves the treatment, it will become the first ultra-long-acting biologic for type 2 inflammation space with six-month dosing potential.