Agios Pharmaceuticals presented 52-week Phase 3 RISE UP trial results at EHA 2026 showing mitapivat significantly improved hemoglobin and reduced transfusion burden in sickle cell disease, supporting FDA sNDA review.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
At the 31st European Hematology Association (EHA) Congress in Stockholm, Agios Pharmaceuticals presented detailed 52-week results from the global Phase 3 RISE UP trial (NCT05031780) evaluating mitapivat in patients aged 16 years and older with sickle cell disease (SCD).
The oral pyruvate kinase (PK) activator met its primary endpoint of hemoglobin response, demonstrating rapid and durable improvements in hemoglobin concentration and indirect bilirubin, a marker of red blood cell destruction.
Secondary Endpoints and Clinical Outcomes
While the study did not achieve statistical significance for reductions in annualized sickle cell pain crises (SCPCs) or patient-reported fatigue in the overall population, further analyses showed meaningful clinical benefits among patients who achieved a hemoglobin response. Responders experienced improvements in fatigue, pain, sleep quality, and physical functioning, suggesting that enhanced hemoglobin levels may translate into quality-of-life benefits.
Reduction in Transfusion Burden
New analyses demonstrated a clinically meaningful reduction in transfusion requirements. Patients treated with mitapivat experienced a 41.1% relative reduction in the need for blood transfusions compared with placebo (23.9% vs. 40.6%). The average number of red blood cell units transfused per patient was reduced by 55.9% (0.70 vs. 1.59 units).
Hemoglobin Responders: Subgroup Benefits
A post-hoc analysis showed that 40.6% of patients receiving mitapivat achieved a hemoglobin response, defined as an increase of at least 1.0 g/dL, compared with 2.9% of patients receiving placebo (p<0.0001). Responders achieved a mean hemoglobin increase of 1.6 g/dL between weeks 24 and 52. Responders demonstrated a 26% reduction in annualized SCPC rates and a 34% reduction in SCPC-related hospitalizations.
Safety and Long-Term Experience
According to trial investigator Dr. Biree Andemariam, mitapivat’s robust anti-hemolytic profile delivers durable improvements in hemoglobin and bilirubin levels while reducing reliance on supportive care measures such as transfusions. Agios Chief Medical Officer Dr. Sarah Gheuens noted that the findings build on more than a decade of clinical experience with mitapivat across hemolytic anemias, supported by a safety database exceeding 1,300 patient-years.
Trial Design and Extension
The Phase 3 RISE UP trial enrolled 207 participants randomized in a 2:1 ratio to receive mitapivat 100 mg twice daily or placebo during a 52-week double-blind treatment period. Among participants who completed the study, 99% elected to continue into the ongoing 216-week open-label extension.
Regulatory Pathway
Agios submitted a supplemental New Drug Application (sNDA) to the U.S. FDA in May 2026 seeking accelerated approval of mitapivat for sickle cell disease, potentially bringing a first-in-class oral PK activator to patients with this chronic and life-threatening disorder.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.