Novel Agent Validates Hepicidin-Agonist Approach in Polycythemia Vera

Naseema Gangat, MBBS, spoke with CancerNetwork® at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting about data from the phase 2 RESTORE-PV trial (NCT06985147) evaluating DISC-3405 for patients with polycythemia vera who require regular phlebotomy. Specifically, she discussed how the novel TMPRSS6-targeting monoclonal antibody may compare with options like rusfertide (Mimrylo).

According to Gangat, a professor of medicine and a consultant in hematology at Mayo Clinic Comprehensive Cancer Center, DISC-3405 may eliminate or reduce the need for phlebotomy in patients while offering less frequent dosing and fewer injection site reactions. Regarding other standards of care in the field, she noted that DISC-3405 would serve as an adjunctive therapy rather than replace strategies like interferon or hydroxyurea.

Transcript:

Regarding RESTORE-PV, how do you think about DISC-3405 relative to rusfertide? Do you see it as a competitor, a next-generation improvement, or simply a validation of the hepcidin-agonist approach in polycythemia vera?

I would say it is both. It validates that increasing hepcidin levels in patients with [polycythemia vera], which was already noted from rusfertide data, restricts [iron] and reduces or eliminates phlebotomy in patients. This is once again proof of principle that we’re hitting the right target. In terms of next-generation [improvements], that is a good question. It has an improved safety profile, particularly with respect to injection site reactions, and the dosing is less frequent.

What would you want to see in terms of thrombosis and long-term outcome data before considering this a real alternative to hydroxyurea or interferon in higher-risk polycythemia vera?

We do not think that this drug would replace the use of interferon or hydroxyurea. If interferon or hydroxyurea is indicated in patients at a high risk of thrombosis, we should be prescribing those agents. But if, for example, the patients are intolerant or do not wish to be exposed to chemotherapy, then there may be a role. But in that situation, you may want to fortify the use of antithrombotic strategies, such as using aspirin in combination with low-dose anticoagulation. We do not think that this agent by itself would replace; it’s more of an adjunctive therapy to existing cytoreductive therapies.

Reference

Gangat N, Tefferi A, Gerds AT, et al. Restore-PV: a phase 2 open-label study evaluating the safety and efficacy of the anti-TMPRSS6 monoclonal antibody DISC-3405 in participants with polycythemia vera. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MPN-099.