Massachusetts-based Disc Medicine (Nasdaq: IRON) released Phase II data showing that DISC-3405, an anti-TMPRSS6 monoclonal antibody, sharply reduced phlebotomy requirements in polycythemia vera (PV) patients, providing early clinical evidence that boosting endogenous hepcidin through TMPRSS6 inhibition can support hematocrit control. The results, presented at the Society of Hematologic Oncology annual meeting in Houston, arrive less than two weeks after Takeda received FDA approval for Mimrylo (rusfertide) in PV — making the competitive landscape suddenly more crowded for a disease that had seen little therapeutic innovation for years.
DISC-3405 targets TMPRSS6, a serine protease that suppresses hepcidin production in the liver. By blocking TMPRSS6, the antibody raises hepcidin levels, restricting iron availability and thereby limiting the excess red blood cell production that drives PV pathology.
In the RESTORE-PV Phase II open-label trial, 40 adult PV patients were enrolled across two cohorts receiving DISC-3405 subcutaneously at 300 mg every two weeks (Cohort A) or every four weeks (Cohort B). Among the 13 Cohort A participants who completed 26 weeks of follow-up, mean phlebotomy events fell from 4.0 in the 26-week baseline period to 0.6 post-treatment (p<0.0001), with 61.5% remaining entirely phlebotomy-free. Of the nine patients who completed the first maintenance period (weeks 12–32), 77.8% were phlebotomy-free. Mean hematocrit was maintained stably below 45% through week 26, accompanied by an initial improvement in symptom burden. The drug was generally well-tolerated, with a low rate of mild, self-limited injection site reactions; adverse events were otherwise consistent with underlying disease. Cohort B efficacy data were not yet mature at the data cut.