Dr Gangat on Phase 2 Efficacy and Safety Data for DISC-3405 in Polycythemia Vera

Despite the use of cytoreductive therapy, if [patients] have frequent phlebotomy needs, this class of drugs would have a role.

Naseema Gangat, MBBS, a professor of medicine and consultant in hematology at Mayo Clinic and a member of the Mayo Clinic Comprehensive Cancer Center, discussed initial results from the ongoing phase 2 RESTORE-PV study (NCT06985147) evaluating the anti-TMPRSS6 monoclonal antibody DISC-3405 in patients with polycythemia vera (PV), which were presented at the 2026 SOHO Annual Meeting. She also dived into the drug’s potential role alongside phlebotomy and cytoreductive therapy in the management of PV.

The trial enrolled 2 cohorts testing different dosing schedules of DISC-3405: cohort A received DISC-3405 at 300 mg every 2 weeks (n = 20) after initial escalating doses of 150 mg and 300 mg given 4 weeks apart (n = 4) or 2 300-mg doses 4 weeks apart (n = 16); and cohort B received 300 mg every 4 weeks (n = 20). The study spans 52 weeks, with an option for responders to continue treatment for up to 2 additional years, she noted.

Mature efficacy data are available for cohort A, according to Gangat. Among the 9 patients who completed the first maintenance phase, 7 (77.9%) became phlebotomy-free, and this elimination of phlebotomy correlated with improved patient-reported outcomes, including reductions in fatigue and Myeloproliferative Neoplasm Symptom Assessment Form scores, she said. Among the 13 cohort A patients who completed 26 weeks of treatment, 8 (61.5%) were phlebotomy-free, and this group experienced a mean reduction in phlebotomy from baseline to week 26 of –3.4 events (95% CI, –4.5 to –2.3), Gangat added.

Gangat framed this drug class as an adjunct to current PV treatment. All patients with PV take aspirin daily, she explained, and a substantial proportion of higher-risk patients, including older patients and those with a thrombosis history, are on cytoreductive therapy. Despite cytoreductive therapy, patients with frequent phlebotomy needs could still benefit from DISC-3405, according to Gangat, and it may have a greater role in patients who are intolerant of phlebotomy or in younger patients who wish to avoid cytoreductive therapy but have frequent phlebotomy needs. In patients already receiving cytoreductive therapy, she added, the agent could potentially help optimize dosing so that phlebotomy is no longer required.