Deciphera Doses First Patient in Pivotal Phase 3 INTREPID Study of Sapablursen in Polycythemia Vera
核心洞察
Deciphera Pharmaceuticals (搜索), a member of Ono Pharmaceutical, announced the first patient dosed in the global pivotal Phase 3 INTREPID study of sapablursen in polycythemia vera (搜索).
The trial compares sapablursen to placebo over a 32-week double-blind period, followed by up to 124 weeks of open-label treatment, with phlebotomy-free response as the primary endpoint.
Sapablursen, designed to reduce TMPRSS6 (搜索) and raise hepcidin, holds FDA Fast Track and Orphan Drug designations from 2024 and Breakthrough Therapy Designation from 2025.
Deciphera Pharmaceuticals (搜索), LLC, a member of Ono Pharmaceutical Co., Ltd., announced that the first patient has been dosed in the global pivotal Phase 3 INTREPID study evaluating sapablursen for the treatment of polycythemia vera (搜索) (PV). Sapablursen is an investigational drug that has the potential to offer a once-monthly treatment option for patients with PV, a rare and potentially life-threatening hematologic disease.
The company framed the milestone around prior Phase 2a data. "We look forward to building upon the positive efficacy and safety results from the Phase 2a IMPRSSION study, which demonstrated the ability of sapablursen to reduce the frequency of phlebotomy, control hematocrit, and improve PV symptoms in patients treated with phlebotomy alone and those on cytoreductive therapies," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "Sapablursen has the potential to be an important new treatment option for patients with PV, and we are excited to begin our Phase 3 INTREPID study, which brings us one step closer to addressing the unmet needs of these patients."
Trial Design and Endpoints
INTREPID is a pivotal global Phase 3 study in patients with phlebotomy-dependent PV, designed to compare the efficacy and safety of sapablursen to placebo over a 32-week double-blind treatment period followed by up to 124 weeks of open-label treatment. The primary endpoint is response, defined by the absence of phlebotomy eligibility.
Key secondary endpoints include the number of phlebotomies — which is the primary endpoint for the European Medicines Agency for potential regulatory approval — hematocrit control, and improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Total T-score and the Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score. Durability of response will be evaluated in patients randomized to sapablursen over 52 weeks of study treatment, comprising 32 weeks of blinded treatment and 20 weeks of open-label treatment.
The INTREPID clinical trial has initiated in the United States and is planned in additional regions including North America, Latin America, Asia Pacific and Europe. Further information on the study is available at ClinicalTrials.gov under identifier NCT07429266.
Mechanism and Regulatory Designations
Sapablursen is designed to reduce the production of TMPRSS6 (搜索), resulting in increased expression of hepcidin, the key regulator of iron homeostasis. By increasing the production of hepcidin, sapablursen has the potential to positively impact PV by decreasing hematocrit, reducing the need for phlebotomy, and improving quality of life.
The U.S. Food and Drug Administration granted sapablursen Fast Track designation and Orphan Drug Designation in 2024, and Breakthrough Therapy Designation in 2025. Sapablursen was discovered and advanced through Phase 2 clinical development by Ionis Pharmaceuticals. Ono obtained exclusive global rights for the development and commercialization of sapablursen after entering into a license agreement with Ionis in March 2025.
Unmet Need in Polycythemia Vera
Polycythemia vera (搜索) is characterized by the overproduction of red blood cells, which significantly increases the risk of serious blood clots, heart attack, stroke, and death. The primary treatment goal in PV is to maintain blood hematocrit levels below 45% to prevent thrombotic events and alleviate burdensome symptoms, such as severe fatigue, difficulty concentrating, night sweats, and pruritus. According to the company, current treatment options often worsen symptoms and inadequately maintain hematocrit control.
Deciphera, a biopharmaceutical company focused on discovering, developing, and commercializing new medicines in cancer, neurologic, and autoimmune disease, is leveraging its proprietary switch-control kinase inhibitor platform. Its approved products include QINLOCK (ripretinib) for adult patients with advanced gastrointestinal stromal tumor (搜索) (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib, and ROMVIMZA (vimseltinib) for adult patients with symptomatic tenosynovial giant cell tumor (搜索) (TGCT) in specified settings. Ono targets areas of unmet medical need including oncology, immunology and inflammation, and neurology, and is accelerating clinical development and commercial operations in the US and Europe through its affiliate Deciphera.