According to findings from the phase III VERIFY trial reported by Kuykendall et al in the Journal of Clinical Oncology, the addition of the hepcidin mimetic rusfertide to standard-of-care therapy significantly improved hematocrit control, reduced the need for phlebotomy, and improved patient-reported symptoms in patients with polycythemia vera, a myeloproliferative neoplasm characterized by erythrocytosis. The researchers reported that significantly more patients receiving rusfertide achieved a clinical response compared with those receiving placebo.
Study Details
VERIFY is an ongoing, international, three-part phase III trial conducted at 102 centers in 19 countries. The randomized, double-blind, placebo-controlled portion (Part 1a) included 293 adults with polycythemia vera who required frequent phlebotomy despite standard-of-care treatment. Patients were randomly assigned 1:1 to receive weekly subcutaneous rusfertide (n = 147) or placebo (n = 146), with or without concurrent cytoreductive therapy. Rusfertide dosing was individualized to achieve and maintain hematocrit levels below 45%. At baseline, 55% of patients were receiving cytoreductive therapy, and 45% were receiving phlebotomy alone.
The primary endpoint was clinical response, defined as the absence of phlebotomy eligibility or specified intercurrent events, which can affect the interpretation of outcomes, during weeks 20 to 32. Key secondary endpoints included the number of phlebotomies, maintenance of hematocrit below 45%, and changes in patient-reported fatigue and symptom burden through week 32. All patients continuing beyond week 32 received open-label rusfertide.
Key Results
The primary endpoint was met, with 77% of patients receiving rusfertide achieving a clinical response compared with 33% receiving placebo (P < .0001). The difference in response rates was 43.8 percentage points (95% confidence interval [CI] = 33.5–54.2). Benefits were consistent across prespecified subgroups, including patients receiving phlebotomy alone (82% vs 33%) and those receiving concomitant cytoreductive therapy (73% vs 33%).
During the 32-week double-blind period, the mean number of phlebotomies was 0.5 with rusfertide vs 1.8 with placebo (P < .0001). Overall, 73% vs 22% of patients, respectively, required no phlebotomies. Hematocrit levels remained below 45% in 63% of rusfertide-treated patients compared with 14% of placebo-treated patients (P < .0001).
Rusfertide also significantly improved patient-reported fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a (P = .0252), and overall symptom burden, as measured by the Myelofibrosis Symptom Assessment Form (P = .0240).
Responses were durable through week 52. Among patients initially assigned to rusfertide who achieved the primary endpoint, 84% maintained their response during weeks 32 to 52. Additionally, 78% of patients who switched from placebo to rusfertide achieved a response during weeks 40 to 52.
The most common adverse events were injection-site reactions, anemia, and fatigue, primarily of grade 1 or 2 severity. During the double-blind period, grade 3 adverse events occurred in 9% of rusfertide-treated patients and 7% of placebo-treated patients. No deaths were reported.
The investigators concluded: “Rusfertide significantly improved hematocrit control, reduced the need for phlebotomy, and improved patient-reported symptoms versus placebo in phlebotomy-dependent patients with [polycythemia vera] who were also receiving standard-of-care therapy.”
Andrew T. Kuykendall, MD, of Moffitt Cancer Center, Tampa, Florida, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Protagonist Therapeutics, Inc. For full disclosures of the study authors, visit ascopubs.org.
