Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV).

This is the authors' abstract. We don't add key points for this paper.

LBA3 Background: PV is characterized by red blood cell overproduction. Rusfertide is a subcutaneous (SC), self-injected, first-in-class peptide hepcidin mimetic that decreases erythrocytosis. VERIFY (NCT05210790) is a global, ongoing phase 3 study designed to assess rusfertide vs PBO in phlebotomy (PHL)-dependent patients (pts) with PV receiving standard of care (SOC) therapy. Methods: In VERIFY Part 1a (Weeks [Wks] 0-32), pts requiring frequent PHL with or without stable cytoreductive therapy (CRT) to control hematocrit (Hct) were randomized (1:1) to receive once-weekly rusfertide or PBO. Pts were stratified by concurrent PV therapy. All pts completing Part 1a were eligible for open-label rusfertide in Part 1b (Wks 32-52). Pts who completed Part 1b were eligible to continue receiving rusfertide. The primary efficacy endpoint was the proportion of pts achieving a clinical response (ie, absence of PHL eligibility and no PHLs from Wks 20-32, and Part 1a completion). Key secondary endpoints (Wks 0-32) included mean number of PHLs, proportion of pts with Hct <45%, and mean change from baseline at end of Part 1a (Wk 32) in the (1) PROMIS Fatigue Short Form 8a (SF-8a) total T-score and (2) MFSAF v4.0 Total Symptom Score (TSS). Results: A total of 293 pts (male, 73.0%; median age, 57 [27-86] years) were randomized to receive rusfertide (n=147) or PBO (n=146). In the rusfertide and PBO groups, 56.5% (n=83) and 55.5% (n=81) of pts, respectively, received concurrent CRT. During Wks 20-32, significantly more pts in the rusfertide group (76.9%) achieved a clinical response vs PBO (32.9%) (p<0.0001). The mean (SE) number of PHLs (Wks 0-32) was 0.5 (0.2) with rusfertide vs 1.8 (0.2) with PBO (p<0.0001). More pts treated with rusfertide maintained Hct <45% from Wks 0-32 vs PBO (rusfertide, 62.6%; PBO, 14.4%; p<0.0001). For patient-reported outcomes (PROs), pts treated with rusfertide demonstrated a statistically significant improvement in the PROMIS Fatigue SF-8a total T-score and MFSAF TSS (p<0.03). During Part 1a, the most common treatment-emergent adverse events (AEs) in the rusfertide and PBO groups, respectively, were injection site reactions (55.9% and 32.9%), anemia (15.9% and 4.1%), and fatigue (15.2% and 15.8%). Serious AEs occurred in 3.4% (rusfertide) and 4.8% (PBO) of pts; none were considered related to rusfertide. During Part 1a, new malignancies were reported in 1 (rusfertide) and 7 (PBO) pts. Conclusions: In pts with PV receiving SOC, rusfertide resulted in a statistically significant reduction in the mean number of PHLs and improved Hct control. Rusfertide is the first investigational agent to target the hepcidin pathway to control Hct and the first agent to prospectively demonstrate a statistically significant improvement in the PROMIS Fatigue SF-8a and MFSAF PROs in pts with PV. Rusfertide had a safety and tolerability profile consistent with rusfertide in prior studies. Clinical trial information: NCT05210790 .