Q4 2026 Preview: 7 FDA Decisions to Watch

Q4 opens with a concentrated slate of regulatory decisions spanning hepatology, nephrology, cardiovascular disease, endocrinology, and dermatology. October begins with what could be a first-in-class hepatology approval as the US Food and Drug Administration (FDA) weighs bepirovirsen for chronic hepatitis B (CHB). The antisense oligonucleotide (ASO) is positioned as the first therapy to deliver clinically meaningful functional cure rates.

November brings a cluster of decisions:

• Obinutuzumab, which could become the first FDA-approved therapy for primary membranous nephropathy
• Povetacicept, a potential second dual BAFF/APRIL inhibitor for immunoglobulin A nephropathy (IgAN)
• Asundexian, Bayer's oral factor XIa (FXIa) inhibitor for secondary stroke prevention

December closes the quarter with 3 decisions. The FDA will reconsider relacorilant for Cushing syndrome following a December 2025 complete response letter (CRL). Regulators will also decide whether lorundrostat becomes the second aldosterone synthase inhibitor (ASI) for uncontrolled hypertension. On December 30, they will rule on bezuclastinib, a selective KIT D816V inhibitor, for nonadvanced systemic mastocytosis.

1. Bepirovirsen

Company: GSK

PDUFA Date: October 26, 2026

Indication: CHB

Summary: Bepirovirsen is an investigational ASO designed to target and degrade hepatitis B virus (HBV)-derived RNA transcripts. By degrading these transcripts, it reduces production of viral proteins, including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen. By suppressing HBsAg, the drug may relieve HBsAg-mediated immune tolerance and enable durable immune-mediated control of infection. This mechanism distinguishes bepirovirsen from nucleos(t)ide analogue (NA) therapy, which suppresses HBV DNA replication without meaningfully lowering HBsAg.

GSK licensed bepirovirsen from Ionis Pharmaceuticals in 2019. The FDA granted Fast Track designation in February 2024, followed by Breakthrough Therapy designation and Priority Review with acceptance of the New Drug Application (NDA) in April 2026.

The NDA was supported by data from the phase 3 B-Well 1 and B-Well 2 trials. Both enrolled adults receiving NA therapy with baseline HBsAg ≤3000 IU/mL. Participants received 6 months of bepirovirsen or placebo on top of standard of care, with functional cure assessed at week 72, 24 weeks after stopping all treatment.

In pooled data, 19% (233/1,220) of bepirovirsen recipients achieved functional cure vs 0% (0/614) with placebo (P < .001 in both trials). Functional cure rose to 26% (200/768) among patients with baseline HBsAg ≤1000 IU/mL. GSK reported no new safety signals, with injection site erythema, local pain, and transient hepatic enzyme elevation among the most frequently observed adverse events.

2. Obinutuzumab

Company: GenentechPDUFA Date: November 2026

Indication: Primary Membranous Nephropathy (pMN)

Summary: Obinutuzumab (Gazyva) is a glycoengineered type II anti-CD20 monoclonal antibody designed to deplete B cells. B cells are a key driver of antibody-mediated autoimmune disease. The therapy is approved for chronic lymphocytic leukemia, follicular lymphoma, and active lupus nephritis.

Genentech announced its approval for idiopathic nephrotic syndrome on September 25, 2026, and a decision in systemic lupus erythematosus is expected by December 2026. The FDA granted Breakthrough Therapy designation for pMN earlier in 2026. If approved, obinutuzumab would become the first FDA-approved therapy for the disease.

The supplemental Biologics License Application (sBLA) was supported by data from the phase 3 MAJESTY trial. MAJESTY randomized 142 adults with pMN 1:1 to open-label obinutuzumab or tacrolimus. Complete remission at week 104 reached 36.9% with obinutuzumab vs 5.7% with tacrolimus (adjusted difference, 31.1%; 95% CI, 18.2%-44.0%; P <.001). Obinutuzumab also improved complete or partial remission at week 104. However, the prespecified analysis of sustained estimated glomerular filtration rate (eGFR) decline did not reach statistical significance.

Grade ≥3 adverse events occurred in 22% of obinutuzumab-treated patients vs 19% with tacrolimus, and serious adverse events occurred in 17% vs 14%, respectively, with no new safety signals.

3. Asundexian

Company: Bayer

PDUFA Date: November 2026

Indication: Secondary Stroke Prevention

Summary: Asundexian is an investigational oral FXIa inhibitor. FXIa has emerged as an antithrombotic target because it may contribute more to pathologic thrombosis than to physiologic hemostasis. That profile could allow reduction of ischemic events with less bleeding than traditional anticoagulants.

The FDA granted Fast Track designation to asundexian in 2023 for stroke prevention after noncardioembolic ischemic stroke. In May 2026, the agency granted Priority Review for secondary prevention after noncardioembolic ischemic stroke or transient ischemic attack (TIA).

The NDA was supported by data from the phase 3 OCEANIC-STROKE trial. The trial randomized 12,327 patients to asundexian 50 mg daily or placebo on top of standard antiplatelet therapy, with a median follow-up of 19 months.

Ischemic stroke occurred in 6.2% of the asundexian group vs 8.4% of the placebo group (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P <.001). The incidence of cardiovascular death, myocardial infarction, or stroke was also lower with asundexian. International Society on Thrombosis and Haemostasis (ISTH) major bleeding was similar between groups (1.9% vs 1.7%; cause-specific HR, 1.10; 95% CI, 0.85-1.44). Serious adverse events occurred in 19.2% of the asundexian group and 19.5% of the placebo group.

4. Povetacicept

Company: Vertex Pharmaceuticals

PDUFA Date: November 30, 2026

Indication: IgA Nephropathy (IgAN)

Summary: Povetacicept is an investigational engineered fusion protein and dual inhibitor of the cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). It uses an engineered transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) domain. In preclinical studies, this domain showed improved binding affinity, potency, pharmacokinetics, and tissue distribution compared with other APRIL, BAFF, and dual BAFF/APRIL inhibitors. If approved, povetacicept would follow atacicept (Trutakna), which received accelerated approval on July 7, 2026, as the first BAFF and APRIL inhibitor for IgAN.

The Biologics License Application (BLA) for accelerated approval was supported by a prespecified week 36 interim analysis of the phase 3 RAINIER trial. RAINIER randomized 605 adults to povetacicept 80 mg subcutaneously every 4 weeks or placebo on top of standard care.

Povetacicept achieved a 52.0% reduction in 24-hour urine protein-to-creatinine ratio (UPCR) from baseline, a 49.8% reduction compared to placebo (P <.0001). Galactose-deficient IgA1 fell 77.4% with povetacicept vs a 9.1% increase with placebo. Among patients with baseline hematuria, 85.1% achieved hematuria resolution vs 23.4% with placebo (both P <.0001). Povetacicept was generally safe and well tolerated, with most adverse events characterized as mild to moderate.

5. Relacorilant

Company: Corcept Therapeutics

PDUFA Date: December 17, 2026

Indication: Cushing Syndrome

Summary: Relacorilant is an investigational selective cortisol modulator designed to bind to glucocorticoid receptors without interacting with other hormone receptors. The FDA issued a CRL for the original NDA, announced December 31, 2025. In the letter, the agency acknowledged the pivotal GRACE trial met its primary endpoint and the phase 3 GRADIENT trial provided confirmatory evidence. It still determined additional evidence of effectiveness was needed to establish a favorable benefit-risk assessment.

Corcept resubmitted the NDA on June 17, 2026, with additional analyses of data from the original submission, as requested by the FDA.

The resubmission is based on data from GRACE, GRADIENT, a long-term extension study, and earlier-stage development data. GRACE enrolled 152 patients with hypercortisolism and hypertension, hyperglycemia, or both in a 22-week open-label phase, followed by a 12-week double-blind, randomized-withdrawal phase among responders.

The trial met its primary endpoint: loss of blood pressure control was 83% less likely with continued relacorilant than with placebo (odds ratio, 0.17; P = .02). According to Corcept, relacorilant improves signs and symptoms of the disease without the hypokalemia, adrenal insufficiency, or QT prolongation associated with some currently approved medications.

6. Lorundrostat

Company: Mineralys Therapeutics

PDUFA Date: December 22, 2026

Indication: Hypertension

Summary: Lorundrostat is an investigational, orally administered, highly selective ASI designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. It is being developed for uncontrolled or resistant hypertension, as well as chronic kidney disease and obstructive sleep apnea. In the phase 2 Explore-OSA trial, lorundrostat did not reduce apnea-hypopnea index but did lower blood pressure. If approved, lorundrostat would join baxdrostat (Baxfendy), which the FDA approved on May 18, 2026, as the first ASI for hypertension.

The NDA, for use in combination with other antihypertensive agents in adults, was supported by data from the phase 3 Launch-HTN and phase 2 Advance-HTN trials. Launch-HTN randomized 1083 adults with uncontrolled or treatment-resistant hypertension on 2-5 antihypertensive medications. Participants received placebo, lorundrostat 50 mg daily, or 50 mg with optional uptitration to 100 mg.

Lorundrostat 50 mg reduced automated office systolic blood pressure by 16.9 mm Hg at week 6, a placebo-adjusted reduction of 9.1 mm Hg (95% CI, −13.3 to −4.9; P <.001). Hyperkalemia, hyponatremia, and reduced kidney function occurred more often with lorundrostat, though discontinuations for these events were below 1%.

7. Bezuclastinib

Company: Cogent Biosciences

PDUFA Date: December 30, 2026

Indication: Nonadvanced Systemic Mastocytosis (NonAdvSM)

Summary: Bezuclastinib is an investigational oral, selective type 1 tyrosine kinase inhibitor with activity against KIT D816V. This gain-of-function mutation drives pathology in up to 95% of patients with systemic mastocytosis. Its type 1 binding conformation targets the active kinase state.

The FDA and European Medicines Agency have granted bezuclastinib orphan drug designation for mastocytosis. According to Cogent, the FDA does not plan to hold an advisory committee meeting and has not identified potential review issues. Separately, Cogent has a PDUFA date of November 30, 2026, for bezuclastinib plus sunitinib in gastrointestinal stromal tumors, and it submitted an NDA in advanced systemic mastocytosis in June 2026.

The NDA was supported by data from the phase 2 SUMMIT trial. SUMMIT randomized 179 adults with NonAdvSM and inadequate symptom control on best supportive care 2:1 to bezuclastinib 100 mg once daily or placebo.

At week 24, Mastocytosis Symptom Severity Daily Diary (MS2D2) total symptom score (TSS) fell by 24.3 points with bezuclastinib vs 15.4 points with placebo, a placebo-adjusted difference of −8.9 points (P = .0002). Serum tryptase fell by ≥50% in 87.4% of bezuclastinib-treated patients vs 0% with placebo (P < .0001). Through 48 weeks, 86.2% (81/94) of bezuclastinib-treated patients achieved a ≥30% reduction in TSS. Hair color changes, altered taste, and ALT/AST elevation were more frequent with bezuclastinib, and all discontinuations due to treatment-related adverse events (5.9%) were attributed to transaminase elevations, which resolved.

References

1. Brooks A. FDA Grants Bepirovirsen Breakthrough Therapy Designation, Priority Review for Chronic Hepatitis B. HCPLive. April 28, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-grants-bepirovirsen-breakthrough-therapy-designation-priority-review-for-chronic-hepatitis-b

2. Brooks A. Bepirovirsen Achieves 19% Functional Cure in Chronic Hepatitis B. HCPLive. May 29, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/bepirovirsen-achieves-19-functional-cure-in-chronic-hepatitis-b

3. Hillenbrand A. FDA Grants Obinutuzumab Priority Review as Primary Membranous Nephropathy's Potential First Therapy. HCPLive. July 15, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-grants-obinutuzumab-priority-review-primary-membranous-nephropathy-s-potential-first-therapy

4. Hillenbrand A. FDA Approves Obinutuzumab (Gazyva) for Idiopathic Nephrotic Syndrome. HCPLive. September 25, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-approves-obinutuzumab-gazyva-for-idiopathic-nephrotic-syndrome

5. Livingston R. FDA Grants Priority Review to Asundexian for Secondary Prevention After Ischemic Stroke. HCPLive. May 19, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-priority-review-asundexian-secondary-prevention-after-ischemic-stroke

6. Bayer. Bayer Granted Priority Review by U.S. FDA for Asundexian in Patients After a Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack. Business Wire. May 18, 2026. Accessed September 29, 2026. https://www.businesswire.com/news/home/20260518787299/en/Bayer-Granted-Priority-Review-by-U.S.-FDA-for-Asundexian-in-Patients-After-a-Non-Cardioembolic-Ischemic-Stroke-or-Transient-Ischemic-Attack

7. Hillenbrand A. FDA Accepts BLA for Povetacicept in IgA Nephropathy. HCPLive. June 1, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-accepts-bla-for-povetacicept-in-iga-nephropathy

8. Hillenbrand A. RAINIER: Povetacicept Reduces Proteinuria By 52.0%. HCPLive. March 9, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/ranier-povetacicept-achieves-primary-and-all-secondary-endpoints-for-igan

9. Hillenbrand A. FDA Approves Atacicept (Trutakna) for IgA Nephropathy. HCPLive. July 7, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-approves-atacicept-trutakna-for-iga-nephropathy

10. Livingston R. FDA Issues Complete Response Letter for Relacorilant for Hypercortisolism. HCPLive. December 31, 2025. Accessed September 29, 2026. https://www.hcplive.com/view/fda-issues-complete-response-letter-for-relacorilant-for-hypercortisolism

11. Corcept Therapeutics. Corcept Resubmits New Drug Application for Relacorilant as a Treatment for Patients with Cushing's Syndrome. Published June 17, 2026. Accessed September 29, 2026. https://ir.corcept.com/news-releases/news-release-details/corcept-resubmits-new-drug-application-relacorilant-treatment

12. Corcept Therapeutics. Form 8-K, Exhibit 99.1: second quarter 2026 financial results. Filed July 29, 2026. Accessed September 29, 2026. https://www.sec.gov/Archives/edgar/data/0001088856/000162828026050607/cort072926ex991pressrelease.htm

13. Pivonello R, Arnaldi G, Auchus RJ, et al. Efficacy and safety of relacorilant for the treatment of patients with Cushing's syndrome (GRACE): a multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study. Lancet Diabetes Endocrinol. Published online February 20, 2026. doi:10.1016/S2213-8587(25)00362-6

14. Brooks A. Lorundrostat Secures FDA NDA Acceptance for Hypertension, Falls Short in Phase 2 OSA Trial. HCPLive. March 9, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/lorundrostat-secures-fda-nda-acceptance-for-hypertension-falls-short-in-phase-2-osa-trial

15. Saxena M, et al; Launch-HTN Investigators. Lorundrostat in participants with uncontrolled hypertension and treatment-resistant hypertension: the Launch-HTN randomized clinical trial. JAMA. 2025;334(5):409-418.

16. Livingston R. FDA Approves Baxdrostat for Uncontrolled Hypertension on Background Therapy. HCPLive. May 18, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-approves-baxdrostat-uncontrolled-hypertension-background-therapy

17. Johnson V. FDA Accepts NDA for Bezuclastinib in Non-Advanced Systemic Mastocytosis. HCPLive. March 16, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-accepts-nda-bezuclastinib-non-advanced-systemic-mastocytosis

18. Cogent Biosciences. Form 10-Q for the quarter ended June 30, 2026. Accessed September 29, 2026. https://www.sec.gov/Archives/edgar/data/0001622229/000119312526342393/cogt-20260630.htm