VERIFY trial

Background

Phase 3, randomized, double-blind, placebo-controlled trial (Part 1a, 32 wk). N=293 phlebotomy-dependent PV pts with poorly controlled hematocrit despite standard of care. Rusfertide = SC hepcidin mimetic that suppresses erythrocytosis.

Results

Interventions and follow up: Arm A: Rusfertide SC (n=147) ± cytoreductive therapy
Arm B: Placebo (n=146) ± cytoreductive therapy
Primary endpoint: Clinical response (absence of phlebotomy eligibility, wk 20-32)
mFollow up: 32 wk (Part 1a)
Results: Clinical response (primary): 77% (n=113) vs 33% (n=48), P<.0001
Mean phlebotomies: 0.5 vs 1.8, P<.0001
Hct <45% maintained: 63% vs 14%, P<.0001
PROMIS Fatigue SF-8a: improved vs placebo, P=.0252
MFSAF TSS7: improved vs placebo, P=.0240

Adverse events

Most common: injection site reactions, anemia, fatigue
Deaths: none
Grade ≥3 (any): NR in abstract
Discontinuation: NR in abstract

Conclusions

Rusfertide on top of standard of care markedly improved hematocrit control, cut phlebotomy need, and improved fatigue/symptom scores vs placebo in phlebotomy-dependent PV. Supports hepcidin mimetic as a new non-cytoreductive option.

Key Limitations

Only 32-wk placebo-controlled period reported; long-term durability, thrombotic events, and effect on disease progression not addressed. Symptom endpoints had borderline P-values (.02) among key secondaries. Cytoreductive therapy was allowed in both arms (heterogeneous background). Summary from abstract; full-text limitations not reviewed.

Clinical Context

Targets erythrocytosis/phlebotomy need rather than clonal burden. Per public reports, an NDA for rusfertide in PV was accepted with FDA priority review (Mar 2026) and breakthrough therapy designation was granted; approval status not verified at time of drafting. Prior options: phlebotomy, hydroxyurea, ruxolitinib, ropeginterferon.

References