Key Takeaways:
Agios Pharmaceuticals Inc. said 40.6% of sickle cell disease patients on mitapivat achieved a hemoglobin response, versus 2.9% on placebo in the Phase 3 RISE UP trial, with new data showing a clinically meaningful reduction in transfusion burden.
"The RISE UP Phase 3 data showcase the strong anti-hemolytic profile of mitapivat, with rapid and durable improvements in both hemoglobin and indirect bilirubin as well as a meaningful reduction in transfusion burden," Biree Andemariam, professor of medicine at University of Connecticut Health and a trial investigator, said.
Patients on mitapivat had a 41.1% relative reduction in the proportion requiring blood transfusions compared with placebo (23.9% versus 40.6%), and a 55.9% relative reduction in average red blood cell units transfused per patient (0.70 units versus 1.59 units), according to results presented at the European Hematology Association Congress in Stockholm. Hemoglobin responders — those with at least a 1.0 g/dL increase sustained from week 24 through week 52 — experienced a 26% reduction in the annualized rate of sickle cell pain crises (2.20 versus 2.98 for non-responders) and 34% fewer related hospitalizations (1.16 versus 1.76).
Agios submitted a supplemental new drug application to the US Food and Drug Administration in May seeking accelerated approval for mitapivat in sickle cell disease. The company is building on more than a decade of clinical experience with the drug across several hemolytic anemias, supported by over 1,300 patient-years of safety data.
The 52-week double-blind period of RISE UP randomized 207 participants 2:1 to receive oral mitapivat 100 milligrams twice daily or placebo. Among the 176 participants who completed the double-blind period, 174 opted to transition into a 216-week open-label extension. The mean hemoglobin increase among responders was 1.6 g/dL.
Hemoglobin responders also reported greater improvements in fatigue, with a mean change of minus 5.19 points on the PROMIS Fatigue scale versus minus 2.55 for non-responders, exceeding the predefined 4.1-point threshold for clinical meaningfulness. Improvements across pain, sleep and physical function measures were also observed in responders compared with non-responders.
Mitapivat was well-tolerated, with treatment-emergent adverse events reported in 97.1% of the mitapivat arm and 98.6% of the placebo arm. No treatment-related deaths occurred during the trial.
The data validate pyruvate kinase activation as a new treatment approach in sickle cell disease, a rare inherited blood disorder affecting an estimated 100,000 people in the US. The results position Agios to potentially expand mitapivat beyond its approved use in pyruvate kinase deficiency into a much larger patient population. Investors will watch for the FDA's decision on the sNDA, which could come under the agency's accelerated approval pathway.
This article is for informational purposes only and does not constitute investment advice.
