Q4 2025 FDA Preview: 10 Decisions to Watch

The first 3 quarters of 2025 have already been historic for many in medicine, with the US Food and Drug Administration (FDA) clearing the way for new therapies in C3 glomerulopathy, IgG4-related disease, recessive dystrophic epidermolysis bullosa, and even granting the first twice-yearly HIV prevention option.1

The pace has not slowed, and Q4 promises to continue that trajectory with another slate of high-profile decisions across dermatology, immunology, cardiology, rare disease, infectious disease, and beyond.

October will bring rulings in atopic dermatitis, chronic rhinosinusitis, and lupus nephritis—3 areas where unmet need remains elevated. November shifts focus toward rare disease, with decisions pending on a gene therapy for Hunter syndrome and a novel growth-targeted therapy in achondroplasia. December is stacked with some of the year’s most closely watched calls, from new disease-modifying options in hematology and cardiology to the first new gonorrhea antibiotic in decades. The final quarter of 2025 could close out the year with as much impact as the first half delivered.

Here are the 10 FDA decisions to watch for the remainder of 2025, listed chronologically by expected decision date.

10 FDA Decisions to Watch in Q4 2025

1. Roflumilast Cream (Zoryve)
Company: Arcutis Biotherapeutics
PDUFA date: October 13, 2025
Indication: Mild to moderate atopic dermatitis in children 2 to 5 years
Summary:
On February 26, 2025, Arcutis Biotherapeutics announced FDA acceptance of its sNDA for roflumilast cream 0.05%(Zoryve) for the treatment of mild to moderate atopic dermatitis in children ages 2 to 5. The FDA set a PDUFA date of October 13, 2025.

The application is supported by positive results from the pivotal INTEGUMENT-PED Phase 3 trial and long-term extension studies, which showed rapid improvement in AD symptoms, significant reductions in itch, and a favorable safety profile. According to Arcutis, if approved, roflumilast cream 0.05% would provide a non-steroid topical therapy option for the approximately 1.8 million young children in the US living with atopic dermatitis.

2. Tezepelumab (Tezspire)
Company: Amgen/AstraZeneca
PDUFA date: October 19, 2025
Indication: Chronic rhinosinusitis
Summary:
On May 1, 2025, it was announced that the FDA accepted a regulatory submission for tezepelumab (Tezspire), supported by positive results from the Phase 3 WAYPOINT study in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The agency has set a PDUFA target action date of October 19, 2025.

In WAYPOINT, tezepelumab significantly reduced nasal polyp score, nasal congestion, need for surgery (98%), and systemic corticosteroid use (88%) at week 52, with improvements seen as early as weeks 2–4. The safety profile was consistent with its approved indication in severe asthma.

3. Obinutuzumab (Gazyva/Gazyvaro)
Company: Genentech/Roche
PDUFA date: October 2025
Indication: Lupus Nephritis
Summary:
On March 5, 2025, Roche announced the FDA acceptance of its sBLA for obinutuzumab (Gazyva/Gazyvaro) to treat lupus nephritis. Based on positive phase 3 REGENCY trial results, the filing showed that obinutuzumab plus standard therapy achieved significantly higher complete renal response rates versus standard therapy alone.

According to Roche, this marks the first anti-CD20 monoclonal antibody in a phase 3 study to demonstrate a benefit in lupus nephritis. The FDA decision is expected by October 2025, positioning the therapy as a potential new option for preserving kidney function and delaying progression to end-stage disease in this high-risk patient population.

4. RGX-121 (Clemidsogene Lanparvovec)
Company: REGENXBIO
PDUFA date: November 9, 2025
Indication: Mucopolysaccharidosis II (MPS II/Hunter Syndrome)
Summary:
On May 14, 2025, the FDA accepted for review a Biologics License Application (BLA) from REGENXBIO for RGX-121 (clemidsogene lanparvovec), an investigational one-time gene therapy for boys with Mucopolysaccharidosis II (MPS II, Hunter Syndrome). The application has been granted Priority Review with a target action date of November 9, 2025.

RGX-121 is designed to deliver the iduronate-2-sulfatase (IDS) gene directly to the central nervous system, potentially enabling long-term enzyme production and cross-correction across brain cells. If approved, commercialization in the US will be led by NS Pharma, under a 2025 partnership with REGENXBIO.

The therapy has multiple FDA designations, including Orphan Drug, Rare Pediatric Disease, Fast Track, and RMAT, underscoring the high unmet need. No approved therapies currently address the neurological manifestations of MPS II, which typically appear by 18–24 months of age.

5. Navepegritide (TransCon CNP)
Company: Ascendis Pharma
PDUFA date: November 30, 2025
Indication: Achondroplasia
Summary:
On June 2, 2025, Ascendis Pharma announced that the FDA accepted for priority review its NDA for navepegritide(TransCon CNP) for the treatment of children with achondroplasia. The FDA assigned a PDUFA date of November 30, 2025, and stated it does not currently plan to convene an advisory committee meeting.

Navepegritide is a once-weekly prodrug of C-type natriuretic peptide (CNP) designed to provide sustained inhibition of the FGFR3 pathway, which is overactive in achondroplasia. Clinical trials demonstrated benefits beyond growth, including improvements in limb alignment, spinal canal dimensions, and muscle strength compared with placebo.

Achondroplasia, the most common form of disproportionate short stature, is caused by a genetic variant in FGFR3 and can lead to complications affecting the skeletal, muscular, neurological, and cardiorespiratory systems. It is estimated to affect over 250,000 people worldwide.

6. Mitapivat
Company: Agios Pharmaceuticals
PDUFA date: December 7, 2025
Indication: Sickle Cell Disease
Summary:
On September 4, 2025, Agios Pharmaceuticals announced that the FDA has extended the PDUFA goal date for the supplemental New Drug Application (sNDA) of mitapivat PYRUKYND (PYRUKYND) in adult patients with non-transfusion-dependent (NTD) and transfusion-dependent (TD) alpha- or beta-thalassemia. The review deadline was pushed back by three months to December 7, 2025, following the submission of a proposed Risk Evaluation and Mitigation Strategy (REMS) to address potential hepatocellular injury risk.

The application is supported by positive results from the phase 3 ENERGIZE and ENERGIZE-T trials, which demonstrated hemoglobin improvement in NTD patients and significant transfusion reduction in TD patients, respectively. If approved, mitapivat would represent the first disease-modifying oral therapy for adults with thalassemia in the US.

7. Etripamil Nasal Spray (Cardamyst)
Company: Milestone Pharmaceuticals
PDUFA date: December 13, 2025
Indication: Paroxysmal supraventricular tachycardia (PSVT)
Summary:
On July 11, 2025, Milestone Pharmaceuticals announced that the FDA accepted for review its response to the Complete Response Letter (CRL) for etripamil (Cardamyst) nasal spray in paroxysmal supraventricular tachycardia (PSVT). The FDA assigned a new PDUFA action date of December 13, 2025.

The CRL, issued in March 2025, cited Chemistry, Manufacturing, and Controls (CMC) issues, including nitrosamine impurities and the need for a facility inspection, but raised no concerns with clinical safety or efficacy data. Milestone’s resubmission, filed June 13, 2025, addressed these issues by conducting new in-vitro studies to meet updated FDA guidance and transferring testing responsibilities to FDA-inspected vendors.

Etripamil is a novel calcium channel blocker designed as a self-administered, rapid-response nasal spray for patients experiencing PSVT or AFib-RVR episodes, potentially reducing reliance on immediate medical intervention. The original NDA was supported by data from the RAPID trial, which showed significantly higher conversion rates within 30 minutes for etripamil compared with placebo.

8. Zoliflodacin
Company: Innoviva Specialty Therapeutics
PDUFA date: December 15, 2025
Indication: Uncomplicated Gonorrhea
Summary:
On June 10, 2025, the FDA accepted for review an NDA from Innoviva Specialty Therapeutics and the Global Antibiotic Research & Development Partnership (GARDP) for zoliflodacin, a first-in-class, single-dose oral antibiotic for uncomplicated gonorrhea in adults and adolescents ≥12 years. The submission has been granted Qualified Infectious Disease Product (QIDP) designation, providing Priority Review and extended market exclusivity.

According to GARDP, if approved, zoliflodacin would be the first new gonorrhea antibiotic in decades, addressing the urgent need for alternatives as Neisseria gonorrhoeae shows rising resistance to existing therapies, including ceftriaxone. In a pivotal phase 3 trial, zoliflodacin achieved non-inferior cure rates compared to ceftriaxone plus azithromycin and was generally well-tolerated with no serious safety signals.

The therapy has a novel mechanism of action, targeting type II topoisomerase with demonstrated activity against multidrug-resistant strains. Administered as a single oral dose, it offers a simpler alternative for patients who cannot receive intramuscular injections.

Commercial rights are held by Entasis Therapeutics (Innoviva affiliate) in major markets, while GARDP retains rights in low- and middle-income countries to ensure broad global access.

9. Narsoplimab
Company: Omeros Corporation
PDUFA date: December 26, 2026
Indication: Hematopoietic stem cell transplant-associated thrombotic microangiopathy
Summary:
On May 6, 2025, Omeros Corporation announced that the FDA accepted its BLA resubmission for narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA).

The resubmission, filed in March 2025, was classified as a Class 2 resubmission and initially assigned a PDUFA action date of September 25, 2025. Following an FDA information request and Omeros’ subsequent submission of additional materials, the agency extended the deadline to December 26, 2025. The FDA indicated that, if no major deficiencies are identified, labeling discussions are expected to begin no later than October 2025.

The updated filing includes survival analyses comparing narsoplimab-treated patients to external control groups, which demonstrated statistically significant improvements in overall survival, as well as additional data from Omeros’ expanded access program. To date, FDA-requested analyses have been consistent with and supportive of narsoplimab’s benefit profile.

10. Aficamten
Company: Cytokinetics
PDUFA date: December 26, 2025
Indication: Obstructive Hypertrophic Cardiomyopathy
Summary:
On May 1, 2025, Cytokinetics announced that the FDA extended the PDUFA action date for the NDA of aficamten for obstructive hypertrophic cardiomyopathy (oHCM) to December 26, 2025. The extension follows FDA’s request for a REMS, which the company submitted. FDA classified the REMS as a Major Amendment, resulting in the standard 3-month extension. No new clinical data were requested.

The NDA was originally accepted by FDA in December 2024, with a standard review and an initial PDUFA date of September 26, 2025.

The submission is supported by positive results from the Phase 3 SEQUOIA-HCM trial, where aficamten demonstrated statistically significant improvements in exercise capacity, LVOT gradients, NYHA functional class, cardiac biomarkers, and quality of life measures, with a favorable safety profile.

References:

1. Johnson V. Q2 2025 Recap: Top FDA Approvals. Hcplive.com. Published July 6, 2025. Accessed October 1, 2025. https://www.hcplive.com/view/q2-2025-recap-7-top-fda-approvals

2. Arcutis Biotherapeutics. U.S. FDA Accepts Supplemental New Drug Application for Arcutis’ ZORYVE® (roflumilast) Cream 0.05% for the Treatment of Children Aged 2 to 5 with Mild to Moderate Atopic Dermatitis - Arcutis Biotherapeutics. Arcutis Biotherapeutics. Published February 26, 2025. Accessed October 1, 2025. https://www.arcutis.com/u-s-fda-accepts-supplemental-new-drug-application-for-arcutis-zoryve-roflumilast-cream-0-05-for-the-treatment-of-children-aged-2-to-5-with-mild-to-moderate-atopic-dermatitis/

3. Amgen. AMGEN REPORTS FIRST QUARTER 2025 FINANCIAL RESULTS. SEC.gov. Published May 1, 2025. Accessed October 1, 2025. https://www.sec.gov/Archives/edgar/data/318154/000031815425000018/amgn-20250331earningsrelea.htm

4. Genentech. Genentech: Press Releases | Tuesday, Mar 4, 2025. Gene.com. Published March 5, 2025. Accessed October 1, 2025. https://www.gene.com/media/press-releases/15055/2025-03-04/fda-accepts-supplemental-biologics-licen

5. REGENXBIO. REGENXBIO Announces FDA Acceptance and Priority Review of the BLA for RGX-121 for MPS II | Regenxbio Inc. Regenxbio Inc. Published May 13, 2025. Accessed October 1, 2025. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-fda-acceptance-and-priority-review-bla-rgx

6. Agios Pharmaceuticals. Agios Provides Update on U.S. PDUFA Goal Date for PYRUKYND® (mitapivat) in Thalassemia – Agios Pharmaceuticals, Inc. Agios Pharmaceuticals, Inc. Published September 4, 2025. Accessed October 1, 2025. https://investor.agios.com/news-releases/news-release-details/agios-provides-update-us-pdufa-goal-date-pyrukyndr-mitapivat

7. Livingston R. FDA Accepts Response to CRL for Etripamil (Cardamyst) for Treating PSVT. Hcplive.com. Published July 11, 2025. Accessed October 1, 2025. https://www.hcplive.com/view/fda-accepts-response-to-crl-for-etripamil-cardamyst-for-treating-psvt

8. GARDP. Innoviva Specialty Therapeutics Receives FDA New Drug Application Acceptance for Zoliflodacin, a First-in-Class Oral Antibiotic for Uncomplicated Gonorrhoea in Adults. GARDP. Published June 10, 2025. Accessed October 1, 2025. https://gardp.org/innoviva-specialty-therapeutics-receives-fda-new-drug-application-acceptance-for-zoliflodacin-a-first-in-class-oral-antibiotic-for-uncomplicated-gonorrhoea-in-adults/

9. Omeros Corporation. Omeros Corporation - Omeros Corporation Reports Second Quarter 2025 Financial Results. Omeros Corporation. Published August 14, 2025. Accessed October 1, 2025. https://investor.omeros.com/news-releases/news-release-details/omeros-corporation-reports-second-quarter-2025-financial-results

10. Cytokinetics. Cytokinetics Announces New PDUFA Date for Aficamten in Obstructive Hypertrophic Cardiomyopathy. Cytokinetics.com. Published May 1, 2025. Accessed October 1, 2025. https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-New-PDUFA-Date-for-Aficamten-in-Obstructive-Hypertrophic-Cardiomyopathy-05-01-2025/default.aspx