FDA Drug Approval Decisions Expected in September 2025

The Prescription Drug User Fee Act (PDUFA) date refers to the deadline set by the US Food and Drug Administration (FDA) for reviewing a New Drug Application (NDA) or Biologics License Application (BLA) and making a final decision on marketing approval. The typical period for review is 10 months after the drug application has been accepted by the Agency. For drugs that have Priority Review, the review period is reduced to 6 months from the time of application acceptance.

Bumetanide Nasal Spray for Edema Associated With CHF

PDUFA date: September 14, 2025

The FDA is reviewing a nasal spray formulation of bumetanide (RSQ-777), a loop diuretic, for the treatment of edema associated with congestive heart failure (CHF), as well as hepatic and renal disease. The drug is currently available as an oral and injectable therapy.

The NDA for the nasal diuretic is supported by data from a clinical trial that compared the absorption and efficacy of the investigational treatment with oral and intravenous (IV) bumetanide in 68 healthy adults. Study participants aged 18 to 55 years received all 3 forms of the drug in a different order and were monitored for 10 days.

Findings showed urine output was similar when intranasal bumetanide was compared with the oral and IV versions. Similar blood concentrations were observed with the nasal and oral products, though absorption was reported to be 33% faster with the nasal spray.

If approved, the nasal spray formulation would provide an additional option for self-administration in an outpatient setting.

Apitegromab for Spinal Muscular Atrophy

PDUFA date: September 22, 2025

The FDA granted Priority Review to apitegromab for the improvement of motor function in patients with spinal muscular atrophy (SMA). 

Apitegromab is a fully human monoclonal antibody that works by selectively binding to the pro- and latent forms of myostatin in order to inhibit myostatin activation. This binding is expected to improve motor function in SMA patients.

The BLA includes data from the phase 3 SAPPHIRE trial (ClinicalTrials.gov Identifier: NCT05156320), as well as supportive data from the phase 2 TOPAZ trial (ClinicalTrials.gov Identifier: NCT03921528) and the long-term extension ONYX trial (ClinicalTrials.gov Identifier: NCT05626855).

The main efficacy population in SAPPHIRE included 156 patients aged 2 to 12 years. Findings showed patients treated with apitegromab had a statistically significant and clinically meaningful improvement in motor function compared with those who received placebo (primary endpoint; measured by the change from baseline in Hammersmith Functional Motor Scale Expanded total score). 

Clinically meaningful improvements were also observed in the pooled population (patients aged 2 to 21 years) across various subgroups (eg, type of survival motor neuron [SMN]-targeted therapy, age of SMN-targeted therapy initiation) and geographic regions.

Narsoplimab for HSCT-Associated Thrombotic Microangiopathy

PDUFA date: September 25, 2025

The FDA is reviewing the resubmitted BLA for narsoplimab for the treatment of hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA).

Narsoplimab is a human monoclonal antibody that specifically targets mannan-binding lectin-associated serine protease-2. It is designed to prevent complement-mediated inflammation and endothelial damage observed with TA-TMA.

The original BLA submission was supported by data from the phase 2 OMS721-TMA-001 study (ClinicalTrials.gov Identifier: NCT02222545), which evaluated the safety and efficacy of narsoplimab in 28 TA-TMA patients with a large majority having multiple comorbidities.

The resubmitted BLA includes an analysis comparing overall survival in the 28 TA-TMA patients in OMS721-TMA-001 with a cohort of over 100 TA-TMA patients not treated with narsoplimab in an external control HSCT registry. Findings showed a significant reduction in the risk of death among patients treated with narsoplimab vs those who did not receive treatment in the external control group (P <.00001).

The application also includes data from the narsoplimab expanded access program in TA-TMA (ClinicalTrials.gov Identifier: NCT04247906), which further confirmed the overall survival benefit with narsoplimab.

Paltusotine for the Treatment of Acromegaly

PDUFA date: September 25, 2025

The NDA for paltusotine is being reviewed for the treatment and long-term maintenance of acromegaly in adults.

Paltusotine is an orally administered small molecule nonpeptide somatostatin receptor type 2 agonist. The investigational treatment suppresses growth hormone and insulin-like growth factor-1 (IGF-1) levels in acromegaly patients.

The NDA includes data from the phase 3 PATHFNDR-1 (Clinicaltrials.gov Identifier: NCT04837040) and PATHFNDR-2 (ClinicalTrials.gov Identifier: NCT05192382) trials. The PATHFNDR-1 study included patients previously treated with somatostatin receptor ligand therapy, while PATHFNDR-2 enrolled patients who were not pharmacologically treated.

In both trials, participants were randomly assigned to receive paltusotine or placebo once daily. Findings showed significantly more patients treated with paltusotine maintained IGF-1 levels equal to or less than 1 times the upper limit of normal (primary endpoint) compared with those who received placebo. 

If approved, paltusotine would provide a once daily oral option for the control of acromegaly.

Tolebrutinib for Non-Relapsing Secondary Progressive MS

PDUFA date: September 28, 2025

The FDA granted Priority Review to tolebrutinib for the treatment of non-relapsing secondary progressive multiple sclerosis (nrSPMS). Tolebrutinib is a brain-penetrant Bruton tyrosine kinase inhibitor that is designed to target smoldering neuroinflammation. 

The regulatory submission includes data from multiple phase 3 trials: HERCULES (ClinicalTrials.gov Identifier: NCT04411641), GEMINI 1 (ClinicalTrials.gov Identifier: NCT04410978) and GEMINI 2 (ClinicalTrials.gov Identifier: NCT04410991). In HERCULES, treatment with tolebrutinib delayed the time to onset of 6-month confirmed disease progression by 31% compared with placebo (P =.0026). 

The GEMINI 1 and GEMINI 2 trials compared treatment with tolebrutinib with teriflunomide in patients with relapsing MS. Neither trial met the primary endpoint of statistically significant improvement in annualized relapse rates; however in a pooled analysis, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29% (P =.023).

This article originally appeared on MPR