Dr Vachhani on Phase 2 Efficacy/Safety Data for Sapablursen in Polycythemia Vera

Pankit Vachhani, MD, an assistant professor of medicine and an associate scientist of experimental therapeutics at the University of Alabama at Birmingham, reviewed findings from the phase 2 IMPRSSION trial (NCT05143957) evaluating sapablursen (formerly ISIS 702843) in patients with phlebotomy-dependent polycythemia vera (PV).

Findings from the study, initially presented at the 2025 ASH Annual Meeting and Exposition, showed the agent’s ability to reduce phlebotomy requirements, improve symptom burden, and produce sustained hematocrit control with a favorable safety profile. Findings from this study helped inform the ongoing phase 3 INTREPID trial (NCT07429266) that is evaluating sapablursen vs placebo in patients with PV.

IMPRSSION was a multicenter, randomized, open-label study enrolling patients with phlebotomy-dependent PV, and patients were allowed to participate regardless of whether they were receiving concomitant cytoreductive therapy, including hydroxyurea, interferon, or ruxolitinib (Jakafi), Vachhani explained. The study evaluated 2 dosing cohorts of subcutaneous sapablursen administered once every 4 weeks: cohort A received an initial dose of 120 mg, whereas cohort B received 40 mg. He emphasized that the once-monthly dosing schedule differentiates sapablursen from other investigational therapies in this space that require weekly administration.

The trial met its primary end point in both dose cohorts, demonstrating a significant reduction in weekly phlebotomy rate between weeks 17 and 37 compared with baseline. Vachhani noted that the higher-dose cohort achieved a particularly robust response, with phlebotomy requirements decreasing to approximately one-third of baseline levels, representing nearly a two-thirds reduction in phlebotomy burden. He added that symptom improvement, assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score, was also statistically significant in the higher-dose cohort, an outcome he described as clinically meaningful given the substantial symptom burden experienced by patients with PV.

Beyond reductions in phlebotomy frequency, Vachhani highlighted sustained decreases in hematocrit observed with longer follow-up, including updated analyses presented at the 2026 EHA Congress. He also noted dose- and time-dependent increases in serum hepcidin levels, providing pharmacodynamic evidence that sapablursen is producing its intended biologic effect by targeting TMPRSS6 and restoring iron homeostasis.

Regarding safety, Vachhani described sapablursen as generally well tolerated, with few injection site reactions and occasional anemia events consistent with its mechanism of action. He concluded that the phase 2 IMPRSSION results provide strong support for the ongoing phase 3 evaluation of once-monthly subcutaneous sapablursen as a potential new treatment option for patients with phlebotomy-dependent PV.