Disc Medicine RESTORE-PV data show DISC-3405 cut phlebotomy in PV
Disc Medicine has reported initial data from the RESTORE-PV Phase 2 trial of DISC-3405, an investigational anti-TMPRSS6 monoclonal antibody, in patients with polycythemia vera (PV). The results, presented in a poster session at the Society of Hematologic Oncology annual meeting in Houston on 9 September, showed the drug significantly reduced phlebotomy burden and maintained hematocrit control through 26 weeks of treatment.
The readout covered Cohort A, in which 20 patients received DISC-3405 at 300 mg subcutaneously every two weeks after a dose-escalation period. Of the 13 participants who completed 26 weeks of the study, mean total phlebotomy events fell from 4.0 in the 26-week baseline window to 0.6 post-treatment, a difference the company reported as statistically significant (p less than 0.0001). Some 61.5% of those completers remained entirely phlebotomy-free from day one, rising to 77.8% phlebotomy-free during the first maintenance period among those who reached that stage. Mean hematocrit was maintained below 45% through week 26.
Mechanism and clinical context
DISC-3405 works by inhibiting TMPRSS6, a transmembrane serine protease that normally suppresses hepcidin, the key hormone governing iron availability. By blocking TMPRSS6, the antibody raises hepcidin levels and restricts serum iron, which in turn limits the excess red blood cell production that characterises PV. The company in-licensed the asset from Mabwell Therapeutics in January 2023 and has previously established proof-of-mechanism in healthy volunteers.
PV affects approximately 150,000 patients in the United States and a comparable number in Europe. It is a chronic myeloproliferative neoplasm driven predominantly by a JAK2 mutation, and current management relies heavily on phlebotomy and cytoreductive agents such as hydroxyurea or ruxolitinib. A therapy that reduces or eliminates the phlebotomy requirement would address a meaningful quality-of-life burden, given that patients may require multiple venepunctures per year to keep haematocrit in the target range.
John Quisel, President and Chief Executive Officer of Disc Medicine, said iron restriction is proving to be "a transformative treatment approach for a large population of patients with polycythemia vera, with the potential to address their crucial need for hematocrit control while managing symptom burden and reducing reliance on phlebotomy."
Market landscape and next steps
The competitive landscape in PV is dominated by hydroxyurea as a generic standard of care and Incyte's ruxolitinib (Jakafi), which holds approval for hydroxyurea-resistant or intolerant patients. Several investigational agents targeting the JAK-STAT pathway and other mechanisms are in development, but DISC-3405 represents a distinct approach via iron restriction rather than direct myelosuppression, which may offer a differentiated tolerability profile. The company positioned DISC-3405 as the first anti-TMPRSS6 monoclonal antibody to have demonstrated phlebotomy reduction in a clinical PV population, a claim that will attract scrutiny as the full dataset is reviewed.
Safety data presented across both Cohorts A and B showed DISC-3405 was generally well tolerated. Adverse events were consistent with the underlying disease, and injection-site reactions were mild and self-limited.
Disc said it will provide a further RESTORE-PV update by the end of 2026, alongside initial Phase 1b data in sickle cell disease, a second indication for the antibody. The company also expects to share feedback from an end-of-Phase 2 meeting with the FDA regarding its separate myelofibrosis anaemia programme, selcodebart (DISC-0974), and to disclose pivotal development plans before year-end. The two-programme readout at SOHO positions Disc as a focused haematology platform with near-term catalysts in two distinct myeloproliferative neoplasm settings.