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*

HCT, hematocrit. *Adapted from Kremyanskaya, et al.1
Part 2 endpoint (% unless otherwise stated)	Rusfertide (n = 30)	Placebo (n = 29)	p value
Response rate	60	17	0.002
Patients requiring no phlebotomy	93	48	-
Mean absolute change in HCT from baseline (absolute percentage point)	0.3±3.1	2.0±2.6	-
Median time to loss of response (weeks)	Not reached	4.4	-
Median time until phlebotomy requirement and first HCT above 45% (weeks)	8.1	8.1	-

• 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.

Key learnings

Results from the first two parts of the REVIVE trial highlight the potential of rusfertide to achieve and sustain hematocrit control, and reduce both the need for phlebotomy and occurrence of disease-related symptoms in patients with PV. The third part of this trial, an open-label extension period, as well as the phase III VERIFY trial (NCT05210790), are currently ongoing to understand whether rusfertide maintains response. Additional trials should focus on the impact of rusfertide on incidence of thrombotic events to further establish the role of this therapy in the therapeutic landscape.