Agios Pharmaceuticals reported that its oral pyruvate kinase activator, mitapivat, achieved the primary hemoglobin response endpoint in the Phase III RISE UP trial for sickle cell disease, but the drug did not reach statistical significance for reducing annualized pain crises.
In the 207‑patient study, 40.6% of patients receiving mitapivat achieved a hemoglobin response compared with 2.9% on placebo. The annualized rate of sickle cell pain crises was 2.62 for the mitapivat group versus 3.05 for placebo, with a p‑value of 0.1213, falling short of the pre‑specified threshold for significance.
Secondary analyses showed that mitapivat improved hemoglobin concentration and lowered indirect bilirubin, but it did not meet the PROMIS Fatigue endpoint. A post‑hoc analysis revealed that patients who achieved a hemoglobin response experienced clinically meaningful reductions in pain‑crisis frequency and fatigue scores, suggesting a subset of responders may derive greater benefit.
Safety data were consistent with prior studies: serious treatment‑emergent adverse events occurred in 20.3% of mitapivat patients versus 29.0% of placebo patients, indicating a favorable safety profile for the drug in this population.
The mixed efficacy results complicate the regulatory pathway for U.S. approval in sickle cell disease. Agios plans to discuss the data with the FDA in a pre‑sNDA meeting scheduled for Q1 2026. The company’s near‑term catalyst remains the anticipated U.S. approval of its approved product, PYRUKYND, for thalassemia, with a PDUFA goal date of December 7, 2025. Agios’s Q3 2025 earnings beat expectations, driven by strong PYRUKYND revenue growth and disciplined cost management, while maintaining a robust cash position of $1.3–$1.7 billion.
Management emphasized that the hemoglobin response data reinforce mitapivat’s anti‑hemolytic activity and that the company will continue to pursue regulatory approval in sickle cell disease, while also focusing on expanding the thalassemia indication. The company’s pipeline includes tebapivat for myelodysplastic syndromes and preclinical programs such as AG‑236, underscoring its broader strategy to leverage pyruvate kinase activation across hematologic disorders.
The content on BeyondSPX is for informational purposes only and should not be construed as financial or investment advice. We are not financial advisors. Consult with a qualified professional before making any investment decisions. Any actions you take based on information from this site are solely at your own risk.