FDA Drug Approval Decisions Expected in December 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.

Lisocabtagene Maraleucel for Relapsed/Refractory Marginal Zone Lymphoma

PDUFA date: December 5, 2025

The FDA is reviewing the supplemental BLA for lisocabtagene maraleucel (liso-cel), a CD19-directed genetically modified autologous T cell immunotherapy, for relapsed or refractory (R/R) marginal zone lymphoma (MZL) in adults who have received at least 2 prior lines of systemic therapy. 

The sBLA was based on results from the MZL cohort of the open-label, single-arm, phase 2 TRANSCEND FL trial (ClinicalTrials.gov Identifier: NCT04245839). Findings showed in 66 efficacy-evaluable R/R MZL patients treated with liso-cel, the overall response rate was 95.5% (95% CI, 87.3-99.1; P <.0001), with 62.1% of patients achieving a complete response (secondary endpoint; 95% CI, 49.3-73.8; P <.0001). 

Results also showed the 24-month rates for duration of response, progression free survival and overall survival were 88.6% (median follow-up 21.6 months), 85.7% (median follow-up 23.8 months), and 90.4% (median follow-up 24.5 months), respectively. As for safety, liso-cel demonstrated low rates of severe cytokine release syndrome and neurologic events.

Gepotidacin for Uncomplicated Urogenital Gonorrhea

PDUFA date: December 11, 2025

Gepotidacin is a first-in-class triazaacenaphthylene antibiotic under review for the treatment of uncomplicated urogenital gonorrhea in patients aged 12 years and older weighing at least 45kg. It inhibits bacterial DNA replication by blocking 2 different type II topoisomerase enzymes.

The NDA is supported by data from the EAGLE-1 study (ClinicalTrials.gov Identifier: NCT04010539), which compared the safety and efficacy of oral gepotidacin to intramuscular ceftriaxone plus oral azithromycin in adolescent and adult patients (N=628) with uncomplicated urogenital infection caused by Neisseria gonorrhoeae.

Findings showed the trial met its primary endpoint demonstrating the noninferiority of gepotidacin to standard of care gonorrhea treatment. Microbiological success was reported in 92.6% (95% CI, 88.0-95.8) of patients treated with gepotidacin and 91.2% (95% CI, 86.4-94.7) of those who received ceftriaxone plus azithromycin. 

If approved, gepotidacin would provide a new oral option for gonorrhea, a sexually transmitted infection that has been recognized as an urgent public health threat by the US Centers for Disease Control and Prevention.

Lerodalcibep for Patients Requiring LDL-C Reduction

PDUFA date: December 12, 2025

Lerodalcibep is an adnectin-based, small protein-binding, third generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor with an enhanced plasma half-life (between 12 and 15 days). 

It is intended to reduce low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD), or very high or high risk of ASCVD, and primary hyperlipidemia, including heterozygous, and in those 10 years or older with homozygous familial hypercholesterolemia.

The BLA is supported by data from the LIBerate program, which included more than 2300 patients on maximally tolerated statins and other oral agents, who required additional LDL-C reduction. Findings across these 5 trials showed treatment with lerodalcibep led to significant and sustained reductions in LDL-C.

Lerodalcibep is designed for self-administration as a once-monthly subcutaneous injection and does not require refrigeration.

Zoliflodacin for the Treatment of Uncomplicated Gonorrhea

PDUFA date: December 15, 2025

The FDA is reviewing the NDA for zoliflodacin, an oral spiropyrimidinetrione antibiotic, for the treatment of uncomplicated gonorrhea in adults and pediatric patients 12 years and older. In in vitro studies, zoliflodacin was found to be active against multidrug-resistant strains of Neisseria gonorrhoeae, including those resistant to ceftriaxone and azithromycin.

The NDA submission is supported by a comprehensive clinical package that includes a pivotal phase 3 study (ClinicalTrials.gov Identifier: NCT03959527) comparing zoliflodacin with standard of care (intramuscular ceftriaxone plus oral azithromycin) in 930 patients with uncomplicated gonorrhea. 

Findings showed zoliflodacin demonstrated noninferiority in achieving microbiological cure at the urogenital site of infection compared with standard of care. Microbiological cure rates at extragenital sites (rectal or pharyngeal) were also similar between treatment groups.

Depemokimab for Asthma With Eosinophilic Phenotype, CRSwNP

PDUFA date: December 16, 2025

GSK is seeking approval of depemokimab for the add-on maintenance treatment of asthma with type 2 inflammation and for chronic rhinosinusitis with nasal polyps (CRSwNP). Depemokimab is an ultra-long acting biologic with high binding affinity for interleukin-5. This extended half-life allows for twice-yearly (every 6 months) subcutaneous administration.

Findings from the SWIFT-1 (ClinicalTrials.gov Identifier: NCT04719832) and SWIFT-2 (ClinicalTrials.gov Identifier: NCT04718103) trials showed treatment with depemokimab reduced clinically significant exacerbations and hospitalization rates compared with placebo in patients with severe uncontrolled asthma with an eosinophilic phenotype on medium- to high-dose inhaled corticosteroids plus another asthma controller. 

In the CRSwNP studies (ANCHOR-1 [ClinicalTrials.gov Identifier: NCT05274750] and ANCHOR-2 [ClinicalTrials.gov Identifier: NCT05281523]), patients treated with depemokimab had significant improvements in nasal polyp size and nasal obstruction (coprimary endpoints) compared with those who received placebo.

Aficamten in Obstructive Hypertrophic Cardiomyopathy

PDUFA date: December 26, 2025

Aficamten, an oral, small molecule cardiac myosin inhibitor, is under review for the treatment of patients with obstructive hypertrophic cardiomyopathy. The treatment is designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle, thereby suppressing the myocardial hypercontractility associated with hypertrophic cardiomyopathy.

The NDA submission is supported by data from the phase 3 SEQUOIA-HCM trial (ClinicalTrials.gov Identifier: NCT05186818), which included 282 adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction. 

Findings showed treatment with aficamten led to a significant increase in peak oxygen uptake, measured by cardiopulmonary exercise testing, at week 24 compared with placebo. Improvements in cardiac structure, function, and biomarkers were also reported in patients treated with aficamten.

As for safety, aficamten was well tolerated with an adverse event profile comparable to placebo. There were no reports of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction.

Narsoplimab for HSCT-Associated Thrombotic Microangiopathy

PDUFA date: December 26, 2025

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

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 resubmitted BLA includes an analysis comparing overall survival in the 28 TA-TMA patients from the phase 2 OMS721-TMA-001 study (ClinicalTrials.gov Identifier: NCT02222545) 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 (hazard ratio, 0.32 [95% CI, 0.23-0.44]; 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.

Tolebrutinib for Non-Relapsing, Secondary Progressive Multiple Sclerosis

PDUFA date: December 28, 2025

Tolebrutinib is an oral brain-penetrant Bruton tyrosine kinase inhibitor under review for the treatment of non-relapsing, secondary progressive multiple sclerosis (nrSPMS) and to slow disability accumulation independent of relapse activity in adult patients.

The NDA submission is supported by data from the phase 3 HERCULES (ClinicalTrials.gov Identifier: NCT04411641), GEMINI 1 (ClinicalTrials.gov Identifier: NCT04410978) and GEMINI 2 (ClinicalTrials.gov Identifier: NCT04410991) trials. In HERCULES, treatment with tolebrutinib delayed the time to onset of 6-month confirmed disability progression by 31% compared with placebo (P =.003) in patients with nrSPMS. 

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).

Relacorilant for the Treatment of Cushing Syndrome

PDUFA date: December 30, 2025

Relacorilant, a cortisol modulator, is being reviewed by the Agency as a potential treatment for Cushing syndrome (hypercortisolism). The NDA submission is supported by data from the pivotal phase 3 GRACE trial (ClinicalTrials.gov Identifier: NCT03697109) and the confirmatory phase 3 GRADIENT trial (ClinicalTrials.gov Identifier: NCT04308590).

Findings from the GRACE trial showed treatment with relacorilant led to clinically meaningful improvements in hypertension, hyperglycemia, and other symptoms of Cushing syndrome such as body weight, waist circumference, and cognition. These results were supported by data from the GRADIENT trial, which also demonstrated improvements in a broad range of hypercortisolism signs and symptoms.

Regarding safety, no cases of relacorilant-induced hypokalemia, endometrial hypertrophy or related vaginal bleeding, adrenal insufficiency or QT prolongation were reported in these trials.

Tradipitant for Vomiting Associated With Motion Sickness

PDUFA date: December 30, 2025

The NDA for tradipitant for the treatment of vomiting associated with motion sickness is under review by the FDA. Tradipitant, a neurokinin-1 receptor antagonist, was investigated in two phase 3 clinical trials: Motion Syros (ClinicalTrials.gov Identifier: NCT04327661) and Motion Serifos (ClinicalTrials.gov Identifier: NCT05903924). Both trials were conducted under real-world conditions on boats in the coastal waters of the US.

The Motion Syros trial included 365 individuals with a history of prior motion sickness during travel. Findings showed a significant reduction in the incidence of vomiting among patients treated with tradipitant compared with placebo. 

Similarly, in Motion Serifos, 316 participants affected by motion sickness during travel were randomly assigned to receive tradipitant or placebo to evaluate the effect on vomiting. Results showed tradipitant significantly prevented vomiting in these patients compared with placebo. Severe nausea and vomiting was also reduced in the tradipitant group vs the placebo group.

This article originally appeared on MPR