Agios plans sNDA submission for mitapivat in sickle cell disease, supported by RISE UP Phase 2 and 3 data and FDA discussions on accelerated approval.
Written By: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Agios Pharmaceuticals announced that it plans to pursue U.S. accelerated approval for mitapivat in Sickle Cell Disease following a pre-supplemental New Drug Application (sNDA) meeting with the U.S. Food and Drug Administration. The company plans to submit the sNDA in the coming months and is working with the FDA to align on the confirmatory clinical trial required for approval.
The pre-sNDA meeting included discussions on data from the RISE UP clinical program, which consists of both Phase 2 and Phase 3 trials evaluating mitapivat in sickle cell disease. Based on these discussions, the FDA recommended submission of a confirmatory clinical trial proposal to support the accelerated approval pathway.
Mitapivat is an oral pyruvate kinase activator that improves energy production in red blood cells. It increases ATP levels and reduces 2,3-diphosphoglycerate (2,3-DPG), which is associated with sickling of red blood cells. By improving red blood cell health, mitapivat may help reduce complications related to sickle cell disease.
Sickle cell disease is an inherited blood disorder caused by abnormal hemoglobin, which leads to rigid, sickle-shaped red blood cells. These cells can block blood flow and cause hemolytic anemia, pain crises, and long-term organ damage. The disease is associated with significant morbidity and reduced life expectancy.
The Phase 3 RISE UP trial (NCT05031780) evaluated the efficacy and safety of mitapivat in patients aged 16 years or older. A total of 207 patients were randomized in a 2:1 ratio to receive mitapivat (100 mg twice daily) or placebo over a 52-week double-blind period, followed by an open-label extension phase.
Mitapivat demonstrated a statistically significant improvement in the primary endpoint of hemoglobin response, defined as a ≥1.0 g/dL increase in hemoglobin levels from Week 24 through Week 52 compared with placebo. The study also showed a reduction in annualized pain crises, although this endpoint did not reach statistical significance.
Patients who achieved the hemoglobin response experienced improvements in hemoglobin levels along with reductions in pain crises, fewer hospital visits, and improved fatigue. The safety profile of mitapivat was favorable and consistent with previous studies.
The double-blind phase was completed by 87.0% of patients in the mitapivat group and 81.2% in the placebo group, and most patients entered the ongoing open-label extension phase.
“Our engagements with the FDA continue to underscore both the unmet need in sickle cell disease and the importance of advancing new treatment options,” said Sarah Gheuens, Chief Medical Officer and Head of R&D at Agios. She added that the benefits observed in the RISE UP program and ongoing discussions with the FDA support the potential of mitapivat in this disease.
Agios has already submitted its proposal for the confirmatory clinical trial to the FDA. The proposed study includes a different primary endpoint from the RISE UP program and is based on data analyses and regulatory discussions. The company stated that the planned trial is not expected to change its operating expense guidance. Agios is also expanding mitapivat globally, with recent approvals of PYRUKYND in the UAE and AQVESME by the U.S. Food and Drug Administration for thalassemia-related anemia.
References
Agios Advances Mitapivat Toward Potential U.S. Accelerated Approval in Sickle Cell Disease Following Pre-sNDA Meeting with FDA, 31 March 2026, Agios Advances Mitapivat Toward Potential U.S. Accelerated Approval in Sickle Cell Disease Following Pre-sNDA Meeting with FDA
A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP), ClinicalTrials.gov ID NCT05031780, https://clinicaltrials.gov/study/NCT05031780
About the Writer
Dr. Anuja Badgujar, BDS, is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.