Dr Kuykendall on VERIFY Trial of Rusfertide in Polycythemia Vera

Andrew Kuykendall, MD, reviews the design and results of the phase 3 VERIFY trial, which evaluated rusfertide (Mimrylo) added to standard of care versus placebo in patients with phlebotomy-dependent polycythemia vera. The trial supported the FDA approval of rusfertide for polycythemia vera.

Kuykendall, of Moffitt Cancer Center, explains how the study was built to confirm the findings of the phase 2 REVIVE study and walks through the primary end point, key secondary end points, and patient-reported outcomes that defined the trial.

According to Kuykendall, REVIVE was largely a single-agent study that included a unique blinded, placebo-controlled withdrawal component. The key finding from REVIVE was that rusfertide could eliminate the need for phlebotomy and control hematocrit in a sustained fashion. VERIFY was designed to confirm those results.

VERIFY enrolled patients with polycythemia vera who were reliant on phlebotomy to control hematocrit. These patients had at least 3 phlebotomies in the 24 weeks prior to screening or 5 phlebotomies in the past year. Patients could be receiving cytoreductive therapy, including hydroxyurea (Hydrea), interferon, or ruxolitinib (Jakafi), or could be managed with phlebotomy alone. Patients were randomly assigned to receive rusfertide in addition to their current standard of care or placebo. After a 20-week dose titration period, during which patients increased their rusfertide dose to goal levels, the primary end point in the United States was assessed from weeks 20 to 32. This end point measured absence of phlebotomy eligibility.

In the primary analysis, patients randomly assigned to rusfertide met the criteria for absence of phlebotomy eligibility much more often than those assigned to placebo. Key secondary end points assessed hematocrit control in different ways, including the mean number of phlebotomies over the first 32 weeks and consistent hematocrit below 45% without phlebotomy through the first 32 weeks. Kuykendall notes that drastically more patients on rusfertide achieved these end points compared with patients on placebo.

The final 2 key secondary end points were patient-reported outcomes. The first was fatigue, which Kuykendall describes as commonly seen in polycythemia vera and often associated with poor quality of life. The second was the Myelofibrosis Symptom Assessment Form (MF-SAF), which has been validated in prior myeloproliferative neoplasm studies. Rusfertide showed statistically significant improvements in fatigue and disease-related symptoms compared with placebo.

Kuykendall says these results confirm that rusfertide not only controlled hematocrit but also improved patient-reported outcomes, which he calls extremely meaningful to patients.

Following the primary analysis, patients who had been receiving placebo rolled over to rusfertide in part 1B of the study. Kuykendall reports that these patients were also able to achieve hematocrit control and decrease their need for phlebotomy.