FDA Accepts Two NDAs: Rusfertide for Polycythemia Vera, Tirabrutinib for CNS Lymphoma

The U.S. Food and Drug Administration has accepted the New Drug Application and granted Priority Review for rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic for the treatment of adults with polycythemia vera. The FDA has set a Prescription Drug User Fee Act goal date in the third quarter of this calendar year.

Separately, the FDA has accepted for review the New Drug Application for tirabrutinib for the treatment of relapsed or refractory primary central nervous system lymphoma. The NDA has been accepted under the FDA's Accelerated Approval Program, which allows for an earlier approval of treatments for serious conditions that fill an unmet medical need. The FDA has set a Prescription Drug User Fee Act target date of December 18, 2026, for the application.

The rusfertide submission is primarily based on the Phase 3 VERIFY Study, in which rusfertide plus standard of care more than doubled clinical response rates, as well as four-year efficacy and safety data from Phase 2 REVIVE/THRIVE Studies. Rusfertide demonstrated significant improvements in hematocrit control, phlebotomy reduction and patient reported outcomes for patients with polycythemia vera in a pivotal study. In addition to Priority Review, rusfertide has received Breakthrough Therapy designation, Orphan Drug designation and Fast Track designation from the U.S. FDA.

Polycythemia vera is characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, and can result in life threatening thrombotic events. Hematocrit is the ratio of red blood cells to the total amount of blood in the body.

Tirabrutinib is a highly potent Bruton tyrosine kinase inhibitor. The NDA is supported by data from part A of the phase 2 PROSPECT trial (ClinicalTrials.gov Identifier: NCT04947319), which evaluated tirabrutinib monotherapy in adult patients with relapsed or refractory primary central nervous system lymphoma.

Forty-eight participants received tirabrutinib 480mg daily, until disease progression or clinically unacceptable toxicity. The primary endpoint was overall response rate. Interim results, presented at the American Society for Clinical Oncology 2025 meeting, demonstrated that after a median follow-up of 11.5 months, the overall response rate was 67%, with a complete response rate of 44%. Furthermore, median duration of response was 9.3 months, and median time-to-response was 1 month.

Any-grade treatment-emergent adverse events were experienced by 75.0%; these included anemia (18.8%), rash maculo-papular (16.7%), fatigue (14.6%), decreased neutrophil count (14.6%), decreased lymphocyte count (14.6%), pruritus (14.6%), and rash (14.6%). Two patients died of treatment-emergent adverse events, but these were considered unrelated to study treatment.