Agios RISE UP Phase 3 data show mitapivat cuts transfusion burden in SCD

Agios Pharmaceuticals presented detailed Phase 3 results for mitapivat in sickle cell disease (SCD) at the 31st European Hematology Association Congress in Stockholm on 13 June 2026, including new transfusion burden and patient-reported outcome analyses that the company says reinforce its case for accelerated FDA approval.

The RISE UP trial enrolled 207 patients aged 16 and over, randomised 2:1 to receive oral mitapivat 100 mg twice daily or placebo over a 52-week double-blind period. As reported in November 2025, the trial met its primary haemoglobin response endpoint, with 40.6% of patients in the mitapivat arm achieving a rise of at least 1.0 g/dL in average haemoglobin from week 24 through week 52, compared with 2.9% in the placebo arm (p<0.0001). The pain crisis primary endpoint did not reach statistical significance in the overall population.

Transfusion burden and responder analyses

New data presented at EHA 2026 showed that patients on mitapivat had a 41.1% relative reduction in the proportion requiring blood transfusions (23.9% versus 40.6% with placebo), and a 55.9% relative reduction in average red blood cell units transfused per patient (0.70 versus 1.59 units). Agios noted these benefits held regardless of whether patients were co-administered hydroxyurea, one of the standard-of-care options in SCD.

A post-hoc analysis of haemoglobin responders in the mitapivat arm showed a 26% reduction in annualised sickle cell pain crises (2.20 versus 2.98 for non-responders) and a 34% reduction in related hospitalisations (1.16 versus 1.76). Emergency room visits for pain crises fell by 53% in this subgroup. Responders also exceeded the predefined 4.1-point threshold for clinically meaningful improvement on the PROMIS Fatigue 13a scale.

Biree Andemariam, Professor of Medicine at the University of Connecticut Health and a RISE UP investigator, said the results demonstrated "rapid and durable improvements in both haemoglobin and indirect bilirubin as well as a meaningful reduction in transfusion burden," adding that the anti-haemolytic effect was "translating to clear clinical benefits" across pain, sleep, and physical function measures.

The safety profile was consistent with prior mitapivat trials. Treatment-emergent adverse events were reported in 97.1% of the mitapivat arm and 98.6% of the placebo arm, with no treatment-related deaths.

Regulatory and competitive context

In May 2026, Agios submitted a supplemental New Drug Application to the FDA seeking accelerated approval of mitapivat in SCD. The data package underpinning that submission now includes the transfusion and responder analyses presented at EHA 2026, which could strengthen the agency's assessment of clinical meaningfulness, a key consideration under the accelerated approval pathway.

The SCD treatment landscape has expanded considerably in recent years, with voxelotor, crizanlizumab, and, more recently, gene therapies from bluebird bio and Vertex Pharmaceuticals/CRISPR Therapeutics having received US approval. Mitapivat occupies a distinct mechanistic position as an oral pyruvate kinase activator, targeting red blood cell energy metabolism rather than haemoglobin polymerisation or vascular adhesion. Its oral route of administration and the breadth of the RISE UP dataset, which Agios says now encompasses over 1,300 patient-years of safety data across haemolytic anaemias, may differentiate it commercially, particularly in healthcare systems where infusion-based or gene-therapy options are less accessible.

The caveat investors and clinicians will scrutinise is the post-hoc nature of the responder analysis: because haemoglobin response was not pre-specified as a stratification factor for secondary endpoints, the pain crisis and quality-of-life improvements in responders carry a higher interpretive burden than the primary efficacy result. The FDA's accelerated approval decision, and any subsequent full approval requirement tied to overall survival or confirmed clinical benefit, will be the next key milestone for the programme.

Of the 176 patients who completed the double-blind period, 174 elected to continue into a 216-week open-label extension, suggesting strong participant confidence in the therapy and providing Agios with a substantial long-term safety and durability dataset.