Agios says adios to sickle cell program over lackluster phase 2 data

Biotech Agios says adios to sickle cell program over lackluster phase 2 data By Nick Paul Taylor Jul 21, 2026 8:30am Agios Pharmaceuticals sickle cell disease failed trials Biotech A phase 2 study of Agios Pharmaceuticals’ next-generation pyruvate kinase (PK) activator has failed to support continued development in sickle cell disease (SCD), leading the company to ax an indication for the second time in two months. The phase 2 trial randomized 59 people with SCD to receive one of three daily oral doses of tebapivat or placebo. Like Agios’ FDA-approved hemolytic anemia drug Pyrukynd, tebapivat is designed to upregulate PK, a key enzyme in glucose metabolism. Evidence that activating the enzyme reduces sickling of red blood cells has fueled development of PK activators in SCD. Pyrukynd is awaiting FDA approval in SCD, despite generating mixed data, and Novo Nordisk’s etavopivat hit the mark in a phase 3 trial in the indication. But Agios bet that structural features designed to enable once-daily administration, without the need for a dose taper, would differentiate tebapivat. Agios lost the bet. Two months after terminating development of tebapivat in lower-risk myelodysplastic syndromes (LR-MDS), the biotech has abandoned its ambition to bring the candidate to market in SCD. As happened in LR-MDS, underwhelming phase 2 data torpedoed Agios’ hopes of developing tebapivat in SCD. Across the three tebapivat dose cohorts, between 29.4% and 47.1% of patients met the trial’s primary endpoint of hemoglobin response, compared to 33.3% of their peers on placebo. The endpoint looked at the proportion of patients with at least a 1.0 g/dL increase in average hemoglobin concentration from Weeks 10 through 12 compared with baseline. Agios moved Pyrukynd into pivotal SCD development after 46.2%-50% of patients on the twice-daily therapy had a hemoglobin response from Weeks 10 through 12 of a phase 2 clinical trial. Novo Nordisk reported a 73% response rate on etavopivat in a 12-week phase 1 study, spurring research that recently culminated in a 48.7% response rate on the once-daily treatment at Week 24 of a phase 3 trial. While tebapivat is dosed less frequently than Pyrukynd, the phase 2 trial “did not establish the level of differentiation we believe is necessary to support continued development,” Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios, said in a statement. The decision to end the program narrows Agios’ SCD focus to the Nov. 1 decision date for FDA approval of Pyrukynd in the indication. Agios Pharmaceuticals sickle cell disease failed trials Biotech Clinical Data