Rusfertide Keeps Working Where Hydroxyurea Fades: Andrew Kuykendall, MD

When clinicians weigh a new option for polycythemia vera (PV), 2 questions come to mind: how well does it work, and for how long? Andrew Kuykendall, MD, associate member of the Department of Hematology at Moffitt Cancer Center and lead investigator of the phase 3 VERIFY trial (NCT05210790)—data from which supported the FDA approval of the hepcidin mimetic—addresses both.

In an interview with The American Journal of Managed Care^®, Kuykendall noted that although the primary end point of no need for phlebotomy between weeks 20 and 32 was met, durability of the treatment is best demonstrated by its consistency across the study population. More than three-quarter of patients did not meet the criteria for needing a phlebotomy during that window, even though the trial had enrolled patients who had consistently required the procedure. This indicates that rusfertide works for patients broadly rather than only for a subset, he explained.

For durability, Kuykendall pointed to the phase 2 REVIVE trial (NCT04057040) and its long-term extension, THRIVE (NCT05991453). This experience, he said, shows the agent can provide durable responses. He contrasted this with current first-line treatment options. Hydroxyurea typically controls blood counts early but has a waning hematologic response, and pegylated interferon takes longer to produce a response. Kuykendall suggested rusfertide could be used alongside these therapeutics to optimize cytoreductive treatment.

For safety, Kuykendall highlighted 2 findings. First, injection-site reactions. “This is a subcutaneous injection that’s self-administered typically, and so injection-site reactions are common,” he said. These were typically seen earlier in VERIFY, and most were grade 1; they were also manageable and rarely led to discontinuations or treatment holds. Still, he emphasized, patients should be counseled on the possibility.

Anemia is also likely to happen. Because the goal is to bring hemoglobin and hematocrit down, some anemia is expected. He argued it is not truly an adverse reaction unless it becomes severe. Many patients classified as anemic had hemoglobin below the lower limit of normal but hematocrit at goal. Because rusfertide works by restricting iron to the bone marrow, overshooting is possible. Weekly, titratable dosing gives clinicians control, but Kuykendall stressed the importance of monitoring labs during titration and backing off if hemoglobin levels drop excessively.