Rusfertide Improves Hematocrit Control, Reduces Phlebotomy in Polycythemia Vera

Rusfertide (Mimrylo) significantly improved hematocrit control and reduced the need for therapeutic phlebotomy in patients with polycythemia vera (PV), according to findings from the phase 3 VERIFY trial (NCT05210790) published in the Journal of Clinical Oncology.¹

Among 293 phlebotomy-dependent patients randomly assigned to receive the hepcidin mimetic rusfertide (n = 147) or placebo (n = 146), 77% (n = 113) in the rusfertide arm achieved a clinical response compared with 33% receiving placebo during weeks 20 through 32 (P < .0001). Rusfertide reduced the mean number of phlebotomies through week 32 to 0.5 compared with 1.8 with placebo (P < .0001). Additionally, 63% of patients receiving rusfertide maintained hematocrit levels below 45% (n = 91) compared with 14% (n = 21) receiving placebo (P < .0001), and 73% (n = 107) of patients receiving rusfertide remained phlebotomy-free compared with 22% (n = 32) receiving placebo.¹

The FDA approved rusfertide for adults with polycythemia vera on August 28, 2026, supported by data from VERIFY.²

Patient-Reported Symptoms

Regarding secondary outcomes, rusfertide also improved patient-reported outcomes at week 32, including fatigue (P = .0252) and overall symptom burden (P = .0240).

In an interview with Targeted Oncology^TM, Andrew Kuykendall, MD, lead investigator on the VERIFY trial and an associate member in the Department of Hematology at Moffitt Cancer Center, explained, “The last 2 key secondary end points were interesting because they were patient-reported outcomes that were looking at both fatigue, as this is something that’s quite commonly seen in polycythemia vera and often associated with a poor quality of life, as well as the Myelofibrosis Symptom Assessment Form, or MFSAF, which has been validated in prior myeloproliferative neoplasm studies.” Rusfertide’s ability to improve these outcomes “obviously is extremely meaningful to patients,” he said.

Rusfertide Safety Findings

During the randomized part 1a of the VERIFY trial, injection-site reactions and anemia were more common with rusfertide than with placebo. Injection-site reactions occurred in 56% (n = 81) of patients receiving rusfertide compared with 33% (n = 48) receiving placebo, while anemia occurred in 15% (n = 22) and 4% (n = 6), respectively. Fatigue was reported in 16% of patients in each group. Most adverse events were grade 1 or 2 in severity. Serious adverse events occurred in 3% (n = 5) of patients receiving rusfertide and 5% (n = 7) receiving placebo. Overall, 11 patients (4%) discontinued treatment because of adverse events. No deaths were reported during the study.¹

The investigators noted that the 32-week placebo-controlled period limited conclusions about long-term outcomes, including thrombotic events, secondary malignancies, and disease progression. After week 32, patients in both groups received open-label rusfertide, and longer-term follow-up is ongoing.¹

REFERENCES

1. Kuykendall AT, Bankar A, Pettit KM, et al. VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy. J Clin Oncol. 0, JCO-26-00992. doi:10.1200/JCO-26-00992

2. FDA approves first drug of its kind for polycythemia vera, a rare blood disorder. News release. FDA. August 28, 2026. Accessed August 30, 2026. https://tinyurl.com/c56mh86y

3. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. doi:10.1056/NEJMoa1208500

4. Myeloproliferative Neoplasms Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Updated September 27, 2024. Accessed October 19, 2026. https://tinyurl.com/yaww68xw