REVIVE trial: Updated results investigating efficacy and safety of rusfertide in patients with PV

Rusfertide, a novel hepcidin mimetic peptide, has been shown to decrease serum iron levels in healthy individuals, which suggests it may help decrease erythropoiesis in patients with polycythemia vera (PV).¹ The three-part phase II REVIVE trial (NCT04057040), previously reported by the MPN Hub, is an ongoing study evaluating the safety and efficacy of rusfertide in patients with phlebotomy-dependent PV.

Recently, Kremyanskaya et al.¹ published updated results from Parts 1 and 2 in the New England Journal of Medicine, which are summarized below.

Study design¹

• Part 1 of the trial was a 28-week, open-label, dose-finding period where rusfertide was added to patients’ ongoing therapy.
• Part 2 of the trial was a 12-week, double-blind, randomized withdrawal period where patients were randomized 1:1 to receive either rusfertide or placebo.
• The primary endpoint was a response during the randomized withdrawal period.
  • Response was defined as hematocrit control, no phlebotomy, and completion of the 12-week regimen.

Key findings¹

• In total, 70 patients were enrolled in Part 1 and 59 patients in Part 2.
• During Part 1 the need for phlebotomy decreased in all patients after rusfertide treatment.
  • The mean phlebotomy rate decreased from 8.7 during the 28-weeks before the first rusfertide dose to 0.6 after the 28-week treatment period.
  • In total, 83% of patients responded to treatment.
• In Part 2 of the trial, a higher proportion of patients treated with rusfertide achieved a response and did not require phlebotomy vs placebo (Table 1).

Table 1. REVIVE trial Part 2 endpoints*

• All patients across Parts 1 and 2 experienced ≥ 1 adverse event (AE)

• In Part 2, more patients experienced Grade 3 AEs in the placebo group vs in the rusfertide group (9 patients vs 0 patients).

• Injection site reactions were the most common AE; however, all were Grade 1/2 in severity.
• All serious AEs were consistent with PV diagnosis and underlying coexisting conditions.
• There were no clinically significant abnormal safety findings identified.