Sapablursen Shows Promising Results in Phase 2a Trial for Polycythemia Vera, Significantly Reducing Phlebotomy Burden
核心洞察
Deciphera Pharmaceuticals (搜索) announced positive Phase 2a IMPRSSION study results for sapablursen in polycythemia vera (搜索) patients at the 67th ASH Annual Meeting.
The study achieved its primary endpoint, significantly reducing weekly phlebotomy rates from baseline in both treatment cohorts (p<0.0001 and p=0.0001).
Sapablursen demonstrated a favorable safety profile and is planned to advance to Phase 3 trials in 2026 following FDA designations.
Deciphera Pharmaceuticals (搜索), a member of Ono Pharmaceutical Co., Ltd. (搜索), announced positive results from the Phase 2a IMPRSSION study of sapablursen in patients with polycythemia vera (搜索) (PV) at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida. The results demonstrate sapablursen's potential to significantly reduce the phlebotomy burden in patients with this rare hematologic disease.
Study Design and Patient Population
The Phase 2a IMPRSSION study was a multicenter, randomized, open-label trial evaluating the safety and efficacy of sapablursen in patients with phlebotomy-dependent PV. The study enrolled 49 patients across two cohorts: Cohort A (N=32) and Cohort B (N=17). Cohort A initially assessed 120 mg before the dose was reduced to 80 mg, while Cohort B tested 40 mg. Sapablursen was administered subcutaneously every four weeks over a 37-week treatment period, with an endpoint window between weeks 17 and 37, followed by a 36-week treatment extension period.
Primary Efficacy Results
The study achieved its primary endpoint of significantly decreasing weekly phlebotomy rate from baseline to weeks 17-37 in both cohorts. In Cohort A, the phlebotomy rate decreased from 0.15 to 0.05 (p<0.0001), while in Cohort B, it decreased from 0.17 to 0.07 (p=0.0001).
The clinical impact was substantial for patients who completed the 37-week treatment period. The median number of phlebotomies during the last 20 weeks of treatment (weeks 17-37) decreased to 0 and 1.5 phlebotomies in Cohort A and B, respectively, compared to 5 phlebotomies in the 26 weeks prior to treatment for both cohorts.
Mechanism of Action and Secondary Outcomes
Sapablursen caused a dose- and time-dependent increase in hepcidin with a corresponding reduction in hematocrit. The drug is designed to reduce the production of TMPRSS6 (搜索), resulting in increased expression of hepcidin, which is the key regulator of iron homeostasis.
When assessing PV symptoms via the Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF-TSS), the mean change from baseline was statistically significant in Cohort A with a mean change of -6.2, while Cohort B showed a mean change of -2.7 that was not statistically significant.
Safety Profile
Sapablursen was generally safe and well tolerated throughout the study. During the trial, one death occurred due to transformation to acute myeloid leukemia (搜索), which was deemed not related to the study drug. The incidence of injection site reactions was low, with all reactions being mild in severity, not progressive, resolving spontaneously, and not recurring. No laboratory trends suggesting adverse effects on liver or renal function were observed.
Regulatory Status and Development Timeline
Sapablursen has received significant regulatory recognition from the U.S. Food and Drug Administration, including Fast Track designation in January 2024, orphan drug designation in August 2024, and Breakthrough Therapy designation in May 2025. Based on the positive Phase 2a study results, Deciphera plans to initiate a Phase 3 study of sapablursen in patients with PV in 2026.
Clinical Context and Unmet Need
"In the treatment of PV, phlebotomy and cytoreductive therapy are performed as treatments for preventing thrombosis. Phlebotomy is the most common treatment for PV, in which blood is regularly removed from the vein, but it imposes significant physical and psychological burdens on patients," said Tatsuya Okamoto, Corporate Officer / Executive Director, Clinical Development of Ono. "These Phase 2a study results demonstrate the ability of sapablursen to reduce the rate of blood withdrawals and control the hematocrit, which is the percentage of red blood cells in the total blood volume of the body, in phlebotomy-dependent patients including those undergoing cytoreductive therapy."
Polycythemia vera (搜索) 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, especially in critical organs like the lungs, heart and brain. Patients with PV also experience severe iron deficiency and commonly have symptoms of fatigue, which can lead to reduced quality of life.
The results were presented by Ionis Pharmaceuticals (搜索), who discovered and developed sapablursen and conducted the IMPRSSION study. In March 2025, Ionis and Ono entered into a license agreement in which Ono obtained exclusive global rights for the development and commercialization of sapablursen.