お知らせ • Dec 10
Protagonist Reports Final Results From Rusfertide Phase 2 REVIVE Study Showing Durable Hematocrit Control at the ASH 2024 Annual Meeting
Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced details from a poster presentation with final data from the rusfertide Phase 2 REVIVE study. Rusfertide, a mimetic of the natural hormone hepcidin, has potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. The data were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 7-10, 2024. Aaron T Gerds, M.D., Associate Professor in Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute, presented the final data set from the REVIVE Phase 2 study (NCT04057040). The Phase 2 trial consisted of three parts including 70 patients in the dose-finding Part 1 (28 weeks), 59 patients in the blinded, placebo-controlled, randomized withdrawal Part 2 (13 weeks), and 58 patients in the Part 3 Open Label Expansion (OLE, 52 weeks). As of October 18, 2024 (the data cut-off date for presentation at ASH), 50 (71%), 38 (54%), and 17 (24%) patients received rusfertide for =2, =2.5, or =3 years, respectively. Of the 58 patients who entered the REVIVE Part 3 OLE, the median duration of therapy is 131.4 weeks (2.5 years) as of the October 18, 2024 data cut-off; 46 patients have rolled over to the THRIVE study (NCT06033586) and are eligible to receive up to two additional years of rusfertide treatment. Final results show that rusfertide, when added to therapeutic phlebotomy with or without cytoreductive therapy achieved long term durable control of hematocrit below the 45% threshold for over 3 years. Prior to enrollment, the estimated mean phlebotomy rate (EPHL) in patients who enrolled on study was >5/year: In Part 1, the EPHL was <1/year in patients who received rusfertide (N=70). In Part 2 (randomized withdrawal phase), the EPHL was <1/year and approximately 6.1/year in the rusfertide and placebo groups, respectively. For patients who continued to Part 3 (Week 42+), the EPHL remained at <1/year. Increased mean corpuscular volume (MCV)and showed continued improvement and normalization of serum ferritin levels. Platelet levels increased following initiation of rusfertide therapy and stabilized over time; mean leukocyte counts remained stable throughout the study. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)[1],[2] was used to assess mean change from baseline in the individual symptom score in patients with moderate (score, 4-6 of 10) or severe (score, 7-10 of 10) symptoms at baseline. In patients who had moderate or severe symptoms at baseline (=4 of 10), there were significant improvements from baseline in fatigue, early satiety, abdominal discomfort, inactivity, problems with concentration, night sweats, and itching at the end of Part 3. Overall, 18 (26%) patients experienced serious adverse events (SAEs); most SAEs were unrelated and likely associated with the underlying disease. One patient developed acute myeloid leukemia after treatment discontinuation.After more than 150 patient-years of rusfertide exposure, malignancies were reported in 11 patients (9 patients had skin malignancies); all of these patients had risk factors that may have contributed to development of these malignancies. There was no obvious correlation between increased exposure to rusfertide and malignancies reported. Seven thrombotic events (6 arterial and 1 venous) occurred in 6 patients; all had high-risk PV. No thrombotic events have been reported in patients with low-risk PV.