VERIFY phase III part 1a: Rusfertide vs placebo for phlebotomy-dependent PV

Phlebotomy with or without cytoreductive therapy is the current SoC for PV. However, frequent phlebotomy is burdensome for patients and insufficient for achieving sustained Hct control <45%. 

Rusfertide is a first-in-class hepcidin mimetic that demonstrated effectiveness in Hct control in the phase II REVIVE trial (NCT04057040). During the 2025 ASCO Annual Meeting, Andrew Kuykendall presented the latest findings from Part 1a of the phase III VERIFY trial (NCT05210790), which evaluated the efficacy and safety of rusfertide vs placebo in patients with phlebotomy-dependent PV.¹

Patients with PV who required either ≥3 phlebotomies 28 weeks prior or ≥5 phlebotomies 1 year prior to enrollment (N = 293) were randomized 1:1 to receive either rusfertide + SoC (n = 147) or placebo + SoC (n = 146). The primary endpoint for Part 1a (Weeks 0–32) was a clinical response confirmed by Hct ≥48%. Key secondary endpoints included mean number of phlebotomies, proportion of patients with Hct <45%, and the mean change from baseline in PROMIS Fatigue SF-8a and MFSAF TSS7.

Key learnings¹

The primary endpoint was met, with 76.9% vs 32.9% of patients achieving a response in the rusfertide vs placebo group, respectively, during Weeks 20–32 (p < 0.0001). 

During Weeks 0–32, rusfertide was associated with a lower mean rate of phlebotomies vs placebo (0.5 vs 1.8; p < 0.001). 

The proportion of patients maintaining Hct <45% during Weeks 0–32 was higher in the rusfertide vs placebo group (62.6% vs 14.4%; p < 0.0001). 

At Week 32, rusfertide vs placebo showed improvement in the PROMIS Fatigue SF-8a TTS and MFSAF TSS7 (LS mean difference, -1.95; p = 0.0268 and -1.87; p = 0.0239, respectively).

The most common TEAEs in the rusfertide and placebo groups were ISR (55.9% vs 32.9%) and anemia (15.9% vs 4.1%), respectively. Discontinuation rates in the rusfertide and placebo groups were 5.5% vs 2.7%.

Serious AEs occurred in 3.4% vs 4.8% of patients in the rusfertide and placebo groups, while one TE (acute MI) occurred in the rusfertide group.

Rusfertide is effective in managing Hct, with a tolerable safety profile compared with placebo, with the potential to become a new treatment option for patients with PV. Long-term assessment of rusfertide safety will continue in VERIFY Parts 1b and 2.