Deciphera Pharmaceuticals Launches Global Phase 3 INTREPID Trial of Sapablursen for Polycythemia Vera
Deciphera Pharmaceuticals, a member of Ono Pharmaceutical Co., Ltd., has announced a significant milestone in the development of a potential new treatment for polycythemia vera (PV), with the dosing of the first patient in the pivotal global Phase 3 INTREPID clinical trial evaluating sapablursen. The study marks an important advancement for patients living with this rare blood cancer and brings the investigational therapy one step closer to potential regulatory approval.
Sapablursen is being developed as a novel treatment for polycythemia vera and has attracted considerable attention due to its potential to provide a once-monthly therapeutic option for patients who often face a lifelong burden of disease management. The launch of the Phase 3 program follows encouraging results from earlier clinical studies and reflects growing confidence in the therapy’s ability to address key unmet needs in the treatment of PV.
The initiation of the INTREPID trial also represents an important milestone for Deciphera Pharmaceuticals and its parent company, Ono Pharmaceutical, as they continue expanding their presence in hematology and rare disease therapeutics.
Addressing an Unmet Need in Polycythemia Vera
Polycythemia vera is a rare and chronic hematologic malignancy characterized by the overproduction of red blood cells in the bone marrow. The excessive buildup of blood cells can increase blood viscosity, placing patients at heightened risk for serious complications including blood clots, stroke, heart attack, and other potentially life-threatening cardiovascular events.
The disease can also significantly impact quality of life through symptoms such as severe fatigue, headaches, dizziness, itching, night sweats, difficulty concentrating, and enlargement of the spleen. Although available treatments can help manage symptoms and reduce complications, many patients continue to experience disease burden and require frequent interventions to maintain adequate control of their hematocrit levels.
One of the most common treatment approaches for PV involves therapeutic phlebotomy, a procedure in which blood is removed from the body to reduce red blood cell counts and lower hematocrit levels. While effective in controlling blood thickness, repeated phlebotomies can be inconvenient, time-consuming, and physically taxing for patients. Many individuals require ongoing procedures throughout the course of their disease.
As a result, there remains a substantial need for therapies capable of reducing dependence on phlebotomy while providing better disease control and improving patient quality of life.
Sapablursen is being developed specifically to address these challenges and potentially offer a more convenient treatment approach through monthly administration.
Building on Encouraging Phase 2 Results
The decision to advance sapablursen into Phase 3 development follows positive findings from the Phase 2a IMPRSSION clinical study, which provided evidence supporting the drug’s therapeutic potential in patients with polycythemia vera.
According to Deciphera Pharmaceuticals, the Phase 2a study demonstrated encouraging efficacy and safety outcomes across multiple clinically meaningful measures. Investigators observed reductions in the frequency of phlebotomy procedures, improved control of hematocrit levels, and improvements in disease-related symptoms among treated patients.
Importantly, these benefits were seen both in patients who relied primarily on phlebotomy for disease management and in those receiving cytoreductive therapies designed to suppress excessive blood cell production.
Commenting on the launch of the Phase 3 program, Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera Pharmaceuticals, emphasized the significance of the earlier clinical findings and the promise they hold for patients.
Sherman noted that the company is eager to build upon the positive efficacy and safety data generated in the Phase 2a IMPRSSION study. He highlighted the observed reductions in phlebotomy requirements, improvements in hematocrit control, and symptom benefits as important indicators of sapablursen’s potential clinical value.
He further stated that the initiation of the INTREPID study represents a major step toward bringing a potentially important new treatment option to patients living with polycythemia vera and addressing ongoing unmet medical needs within the community.
Overview of the INTREPID Phase 3 Trial
The INTREPID study serves as the pivotal Phase 3 trial designed to evaluate the efficacy and safety of sapablursen in patients with phlebotomy-dependent polycythemia vera.
The global study will compare sapablursen with placebo during a 32-week randomized, double-blind treatment period. Following completion of this phase, participants will be eligible to continue receiving treatment during an open-label extension period lasting up to 124 additional weeks.
The trial has been designed to generate comprehensive clinical data supporting potential regulatory submissions in major markets worldwide.
Researchers will evaluate multiple measures of disease control and patient benefit throughout the study. The primary endpoint focuses on treatment response and is defined by the absence of phlebotomy eligibility during the evaluation period. This endpoint directly reflects one of the most important treatment goals in PV management: reducing the need for repeated blood removal procedures while maintaining safe hematocrit levels.
Several key secondary endpoints will also be assessed. These include the total number of phlebotomies required by patients, which serves as the primary endpoint requested by the European Medicines Agency (EMA) for potential future regulatory review.
Additional secondary measures include hematocrit control, a critical marker of disease management and cardiovascular risk reduction in PV patients.
The study will also assess improvements in patient-reported outcomes, recognizing that symptom burden and quality of life are major concerns for individuals living with the disease.
Measuring Patient-Centered Outcomes
A notable feature of the INTREPID study is its emphasis on evaluating patient-reported experiences alongside traditional clinical endpoints.
Investigators will utilize the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Total T-score to assess changes in fatigue, one of the most common and debilitating symptoms associated with polycythemia vera.
Fatigue can significantly affect daily functioning, productivity, and overall well-being, making it an important measure of treatment effectiveness from the patient perspective.
The study will also incorporate the Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score, a validated tool used to evaluate symptoms commonly experienced by patients with myeloproliferative neoplasms, including polycythemia vera.
By incorporating these assessments, researchers hope to gain a more comprehensive understanding of how sapablursen affects both disease biology and quality of life.
Another important objective of the trial involves evaluating the durability of treatment response. Patients randomized to receive sapablursen will be followed for a total of 52 weeks, including the initial 32-week blinded phase and an additional 20 weeks of open-label treatment.
This extended observation period is intended to determine whether treatment benefits can be maintained over time, a critical consideration for a chronic condition requiring long-term management.
Expanding a Global Clinical Development Program
The INTREPID study is being conducted as a global clinical trial, reflecting the worldwide need for improved treatment options for polycythemia vera.
Patient enrollment has already begun in the United States, where the first participant has now been dosed. Additional study sites are expected to open across multiple regions, including North America, Latin America, Europe, and the Asia-Pacific region.
The broad geographic scope of the study is designed to support global regulatory filings and ensure that data are generated across diverse patient populations.
Through this international approach, Deciphera and Ono aim to establish a robust evidence base capable of supporting future approval applications in major healthcare markets around the world.
Regulatory Momentum Supports Development
Sapablursen has already attracted significant attention from regulators, receiving several important designations from the U.S. Food and Drug Administration (FDA) that underscore both the seriousness of polycythemia vera and the therapy’s potential clinical value.
In 2024, the FDA granted sapablursen both Fast Track designation and Orphan Drug Designation. Fast Track status is intended to facilitate the development and review of therapies that address serious conditions and unmet medical needs, potentially enabling more frequent interactions with regulators and an accelerated development pathway.
Orphan Drug Designation provides incentives aimed at encouraging the development of treatments for rare diseases, including market exclusivity benefits following approval.
Building on this regulatory momentum, sapablursen received Breakthrough Therapy Designation from the FDA in 2025. This designation is reserved for investigational therapies that demonstrate the potential to provide substantial improvement over existing treatments based on preliminary clinical evidence.
The receipt of all three designations reflects growing confidence in the therapeutic promise of sapablursen and may help facilitate its continued development.
From Discovery to Global Development
Sapablursen was originally discovered and advanced through Phase 2 clinical development by Ionis Pharmaceuticals, a company recognized for its expertise in RNA-targeted medicines.
In March 2025, Ono Pharmaceutical entered into a licensing agreement with Ionis, securing exclusive global rights to develop and commercialize sapablursen. Through its subsidiary Deciphera Pharmaceuticals, Ono has since assumed responsibility for advancing the therapy into late-stage development and pursuing potential commercialization worldwide.
The initiation of the Phase 3 INTREPID trial marks the first major development milestone under Ono’s leadership of the program and highlights the company’s commitment to bringing innovative therapies to patients with rare hematologic diseases.
As enrollment progresses and clinical data emerge, the study will play a crucial role in determining whether sapablursen can fulfill its promise as a potentially transformative treatment option for individuals living with polycythemia vera. If successful, the therapy could provide a new once-monthly treatment alternative that reduces reliance on phlebotomy, improves symptom control, and advances the standard of care for this rare and challenging blood disorder.
About Sapablursen
Sapablursen is designed to reduce the production of TMPRSS6 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.
About Polycythemia Vera
Polycythemia vera (PV) is a rare and potentially life-threatening hematologic disease 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 <45% to prevent thrombotic events and alleviate burdensome symptoms, such as severe fatigue, difficulty concentrating, night sweats, and pruritus. Current treatment options often worsen symptoms and inadequately maintain hematocrit control.
About Deciphera Pharmaceuticals, LLC
Deciphera, a member of Ono Pharmaceutical Co., Ltd., is a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines and providing hope to people living with cancer, neurologic, and autoimmune disease. Deciphera is leveraging its proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology to develop a broad portfolio of innovative medicines.
In addition to advancing multiple product candidates from Deciphera’s platform in clinical studies, QINLOCK® (ripretinib) is Deciphera’s switch-control kinase inhibitor approved in many countries including the European Union and the United States for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.
ROMVIMZATM (vimseltinib) is a kinase inhibitor approved in the United States for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability. For more information, visit www.deciphera.com and follow us on LinkedIn and X (@Deciphera).
About Ono Pharmaceutical Co., Ltd.
Ono Pharmaceutical Co., Ltd. delivers innovative medicines for patients worldwide. Upholding its philosophy of “Dedicated to the Fight against Disease and Pain,” Ono targets areas with unmet medical needs including oncology, immunology & inflammation, and neurology, and fosters partnerships with academic and biotech organizations to accelerate drug discovery. Through its affiliate, Deciphera Pharmaceuticals, Ono is accelerating clinical development and commercial operations in the US and Europe to drive global business expansion and further its commitment to patient care.
