Protagonist Therapeutics, Inc. announced details from two abstracts at the European Hematology Association 2024 Congress, including an oral presentation with long-term follow-up data from the Phase 2 REVIVE study with rusfertide, a mimetic of the natural hormone hepcidin with potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. Copies of the presentations will be available on the Events and Presentations section of the Protagonist website. Kristen M. Pettit, M.D., Clinical Associate Professor at University of Michigan Health presented the long-term follow-up data from patients in REVIVE who continued into the open label extension (OLE).

The Phase 2 trial consisted of 3 parts including 70 patients in the dose-finding Part 1 (28 weeks), 59 patients in the placebo-controlled, randomized withdrawal Part 2 (13 weeks), and 58 patients in the Part 3 OLE (52 weeks). The THRIVE study provides OLE for an additional two years of treatment to patients who have completed Part 3 OLE of the Phase 2 REVIVE study. As of April 9, 2024 (data cut-off for the EHA presentation), 47 patients (81.0%) remain on rusfertide, with 48 patients treated for two or more years and 10 patients treated for three or more years.

Of the 58 patients who entered the REVIVE Part 3 OLE, the median duration of therapy is 124.3 weeks as of the April 9, 2024 data cut-off, and 24 patients have rolled over to the THRIVE study for up to two additional years of rusfertide treatment. The updated long-term data showed that rusfertide when added to therapeutic phlebotomy with or without cytoreductive therapy resulted in: Long term durable control of hematocrit below the 45% threshold for up to 3 years; Decreased phlebotomy use, from a rate of 8.7 per year before study entry to 0.43 per year in Part 3 of REVIVE, which remained consistent with the rate of 0.36 per year observed for patients randomized to rusfertide in Part 2 of REVIVE; Decreased red blood cell counts and continued improvement and normalization of serum ferritin levels; Mean leukocyte counts remained stable throughout the study; an asymptomatic increase in platelets was observed with initiation of rusfertide treatment but stabilized over time; No new safety signals with the majority of adverse events being Grade 1-2 injection site reactions or adverse events consistent with the comorbidities commonly associated with polycythemia vera. In REVIVE, 19 of 70 patients (27.1%) had a history of cancer prior to enrolling in the study.

Among these, 10 (14.3%) had a history of skin cancer. As of April 9, 2024, there are 11 patients diagnosed with malignancies while on study (11/70; 15.7%), including 9 with skin cancer (9/70; 12.9%). All cancers occurred in patients with risk factors such as a prior history of cancer, previous cytoreductive therapy, pre-existing skin lesions that were not biopsied or photosensitive skin.

All skin cancers were localized, early stage (in situ or stage 1) and all patients remained on rusfertide after the skin lesions were excised. A separate abstract accepted for publication only was titled ?Absence of QTC Prolongation with Rusfertide, a Hepcidin Mimetic for the Treatment of Polycythemia Vera: A Thorough QT/QTC Study in Healthy Subjects.? In this study, 60 healthy subjects were randomized to receive single doses of subcutaneous rusfertide (90mg), matching placebo, or oral moxifloxacin (400mg).Rusfertide was generally well tolerated and did not result in a clinically relevant prolongation of the QTcF interval.