Updated Long-Term Rusfertide Phase 2 Results Show Durable Hematocrit Control in Protagonist's EHA2024 Report

Protagonist Therapeutics, Inc. recently shared compelling data from the REVIVE Phase 2 study regarding the treatment of polycythemia vera (PV) with rusfertide at the European Hematology Association 2024 Congress. The long-term follow-up data shows promising results in terms of sustained hematocrit (Hct) control, reduced need for phlebotomy, and ongoing safety in patients. These findings were presented by Dr. Kristen M. Pettit, Clinical Associate Professor at University of Michigan Health.

The REVIVE study included 70 patients in the dose-finding Phase 1 (28 weeks), 59 in the placebo-controlled, randomized withdrawal Phase 2 (13 weeks), and 58 in the open-label extension (OLE) Phase 3 (52 weeks). Patients from the OLE phase are eligible to join the THRIVE study, which offers an additional two years of rusfertide treatment. As of April 9, 2024, 47 patients (81%) remained on rusfertide, with 48 patients treated for two or more years and 10 treated for three or more years. The median duration of therapy was 124.3 weeks, and 24 patients moved to the THRIVE study.

Dr. Pettit emphasized the positive long-term impact of rusfertide, highlighting its potential as a significant treatment for PV. The updated data showed that rusfertide, used with therapeutic phlebotomy with or without cytoreductive therapy, effectively managed hematocrit levels below 45% for up to three years. Phlebotomy use decreased from 8.7 times per year before the study to 0.43 in Part 3 of REVIVE, consistent with the 0.36 times per year noted in Part 2. Additionally, there was a reduction in red blood cell counts and an improvement in serum ferritin levels. Mean leukocyte counts remained stable, although an initial increase in platelet counts was observed, which later stabilized.

Safety data indicated no new concerns, with most adverse events being mild injection site reactions or consistent with existing comorbidities associated with PV. Notably, 19 of the 70 patients had a history of cancer, including 10 with skin cancer. During the study, 11 patients were diagnosed with new malignancies, primarily skin cancers. These cases were mostly localized and early-stage, allowing the patients to continue rusfertide treatment after lesion excision.

Dr. Arturo Molina, Chief Medical Officer at Protagonist, underscored the durability of rusfertide's positive effects on PV symptoms and iron deficiency, alongside a solid safety profile. He mentioned that patients completing the three-year OLE could transition to the THRIVE study, potentially extending rusfertide treatment to nearly six years.

In another abstract, a study on the QT/QTc interval in healthy subjects revealed that rusfertide did not cause a clinically relevant prolongation of the QTcF interval, further supporting its safety profile.

Protagonist Therapeutics focuses on developing peptide-based new chemical entities (NCEs) like rusfertide and JNJ-2113, both of which are in advanced clinical stages. Rusfertide, a hepcidin mimetic, is the lead candidate in their global Phase 3 development program. The randomized portion of the Phase 2 REVIVE study has shown positive results and is now in an open-label extension phase. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Rusfertide will be co-developed and co-commercialized with Takeda under a collaboration agreement initiated in early 2024.

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