Disc Medicine's DISC-3405 Cuts Phlebotomy Burden in Phase 2 Polycythemia Vera Trial
核心洞察
Disc Medicine presented initial Phase 2 RESTORE-PV results showing DISC-3405 raised hepcidin and lowered serum iron in patients with polycythemia vera (搜索).
Among 13 Cohort A patients completing 26 weeks, mean phlebotomy events fell from 4.0 at baseline to 0.6 post-treatment (p<0.0001).
Mean hematocrit stayed below 45% through week 26 with initial symptom improvement, and the drug was generally well tolerated.
Disc Medicine, Inc. (NASDAQ: IRON) reported positive initial results from the Phase 2 RESTORE-PV trial of DISC-3405 in patients with polycythemia vera (搜索) (PV), presented in a poster session at the 2026 Society of Hematologic Oncology (SOHO) annual meeting in Houston, Texas, with an oral presentation scheduled for September 10. The data show that the investigational anti-TMPRSS6 (搜索) monoclonal antibody increased hepcidin and lowered serum iron, translating into reduced phlebotomy, controlled hematocrit, and improved symptom burden.
According to the company, DISC-3405 is the first monoclonal antibody targeting TMPRSS6 (搜索) that has demonstrated phlebotomy reduction in patients with PV.
"This first look at data from the RESTORE-PV trial shows that the established pharmacodynamics of DISC-3405 are translating well on important clinical measures," said John Quisel, JD, PhD, President and Chief Executive Officer of Disc Medicine. "Iron restriction is proving to be a transformative treatment approach for a large population of patients with polycythemia vera (搜索), with the potential to address their crucial need for hematocrit control while managing symptom burden and reducing reliance on phlebotomy."
Trial Design and Dosing
RESTORE-PV is a Phase 2, multi-center, open-label trial that enrolled 40 adult participants with PV, including 20 participants in Cohort A and 20 in Cohort B. Following a 4- to 12-week observation period, participants undergo a 12-week dose escalation and then receive DISC-3405 subcutaneously at 300 mg every two weeks (Cohort A) or every four weeks (Cohort B) for 20 weeks, followed by up to 20 additional weeks of treatment at the respective doses.
At the data cut, all 20 participants in Cohort A were dosed, with 13 patients completing 26 weeks of the study; 18 of 20 participants in Cohort B were dosed. Efficacy data were presented for Cohort A, while baseline and safety data were presented for both cohorts. Cohort B efficacy data were not yet mature at the data cut.
Pharmacodynamic and Clinical Results
Across the escalation and maintenance periods, results in Cohort A demonstrated dose-proportional pharmacokinetics, elevation of hepcidin, reduction of serum iron, and an increase in ferritin. Mean hematocrit was maintained stably below 45% through week 26, which the company said led to initial improvement in symptom burden.
For the 13 patients completing 26 weeks of study, mean total phlebotomy events significantly decreased from 4.0 in the 26-week baseline period to 0.6 in the 26 weeks post-Day 1 (p<0.0001). In addition, 61.5% of participants remained entirely phlebotomy-free post-baseline through 26 weeks. Of those who completed the first maintenance period (weeks 12–32, n=9), 77.8% remained phlebotomy-free during that period.
DISC-3405 was generally well tolerated, with adverse events consistent with the underlying disease and a low rate of injection site reactions that were mild and self-limited across both cohorts.
Mechanism and Development Context
DISC-3405 is an investigational anti-TMPRSS6 (搜索) (Transmembrane Serine Protease 6, also known as Matriptase-2) monoclonal antibody designed to increase hepcidin production and suppress serum iron. TMPRSS6 is a serine protease that suppresses hepcidin production in the liver; by blocking it, the antibody raises hepcidin levels, restricting iron availability and thereby limiting the excess red blood cell production that drives PV pathology. Disc in-licensed DISC-3405 from Mabwell Therapeutics (搜索) in January 2023.
The company has established clinical proof-of-mechanism for DISC-3405 in a Phase 1 study in healthy volunteers and has initiated a Phase 2 trial in PV and a Phase 1b trial in sickle cell disease (搜索). Disc received FDA Orphan Drug and Fast Track designations for DISC-3405 in PV, and completed full enrollment of RESTORE-PV ahead of schedule in the second quarter of 2026. DISC-3405 remains investigational and is not approved for use as a therapy in any jurisdiction worldwide.
The readout arrives less than two weeks after Takeda received FDA approval for Mimrylo (rusfertide) in PV on August 28, 2026, a hepcidin mimetic that replaces hepcidin directly rather than inducing endogenous production. PharmaEssentia (搜索)'s Besremi (ropeginterferon alfa-2b-njft), approved in 2021, targets the underlying JAK2-driven clonal expansion. Whether one mechanism confers durable advantages over another in real-world PV management remains an open question requiring head-to-head data that does not yet exist.
Disease Burden and Current Treatment
PV is a chronic and rare myeloproliferative neoplasm characterized by the abnormal proliferation of red blood cells, affecting approximately 150,000 patients in the U.S. with similar prevalence in Europe. The overproduction of red blood cells alters blood viscosity, placing patients at elevated risk of cardiovascular and thromboembolic events such as heart attack and stroke. Patients also experience complications including enlarged spleen and symptoms such as fatigue, pruritis, and difficulty concentrating. Current therapy involves phlebotomy to physically remove blood and iron to limit erythropoiesis, or treatment with cytoreductive agents, with the goal of reducing red blood cell count and managing symptoms.
Additional Presentations and Next Steps
Disc also presented an encore of positive results from the Phase 2 RALLY-MF trial of selcodebart (搜索) (DISC-0974) in patients with anemia of myelofibrosis (搜索) (MF), along with a new systematic literature review characterizing the humanistic burden of anemia associated with MF through patient-reported outcomes.
The company plans to provide an update on RESTORE-PV, as well as initial data from the Phase 1b trial of DISC-3405 in sickle cell disease (搜索), by the end of 2026. For selcodebart (搜索), Disc expects to share feedback from an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (搜索) and plans for pivotal development in anemia of MF by the end of the year.