Agios Pharmaceuticals’ next-generation pyruvate kinase (PK) activator tebapivat has failed a phase 2b study in lower-risk myelodysplastic syndromes (LR-MDS), leading the company to stop pursuing the drug for that indication while continuing development in sickle cell disease (SCD).
The mid-stage trial evaluated tebapivat in 65 patients with LR-MDS and anemia, many of whom had previously received treatment. The 24-week study tested three once-daily oral doses of the therapy. Its primary endpoint measured the number of patients who did not require a blood transfusion for at least eight consecutive weeks.
According to Agios, the study missed its primary endpoint and did not meet the predefined threshold required to continue development in LR-MDS. The company said tebapivat was generally well-tolerated and demonstrated evidence of biological activity, but the results did not show sufficient clinical benefit in this patient population.
LR-MDS is a group of blood cancers in which the bone marrow does not produce enough healthy blood cells. The diseases may progress to leukemia in some cases.
The outcome follows earlier results from the phase 2a portion of the tebapivat program reported in 2023. At that stage, Agios said the therapy showed a meaningful reduction in transfusions among patients with LR-MDS.
“The results from the phase 2b trial underscore the biological complexity of lower-risk myelodysplastic syndromes and the challenges of identifying patients most likely to benefit,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of research and development at Agios, in a May 29 release.
Gheuens also said that PK activation remains a clinically validated mechanism and that the company continues to see significant potential for tebapivat in sickle cell disease.
Despite the setback in LR-MDS, Agios is continuing to evaluate tebapivat in SCD through an ongoing phase 2 study. According to Gheuens, results from that trial are expected in the second half of the year. Another company statement said early results are expected in the second half of 2026.
Tebapivat belongs to a class of medicines known as PK activators, which increase the activity of an enzyme in red blood cells to help them function more effectively.
Agios already markets a PK activator, Pyrukynd, which was approved in 2022 as the first therapy for hemolytic anemia in adults with PK deficiency. However, the company’s efforts to expand its use have seen mixed results. Last year, Pyrukynd reported mixed phase 3 results in sickle cell disease, which dented Agios’ stock. In 2024, a study of Pyrukynd in children with PK deficiency who receive regular transfusions also missed its prespecified statistical criterion.
Agios ended last year with regulatory progress when the U.S. Food and Drug Administration approved Pyrukynd to treat anemia in adults with alpha- or beta-thalassemia under the brand name Aqvesme. The company said the treatment is currently being rolled out following approval last year.
J.P. Morgan analyst Tessa Romero said the outcome of the tebapivat study was not unexpected because the trial involved disease variability and a heavily pre-treated patient population.
Agios Ends Tebapivat Program in LR-MDS
Agios has announced the discontinuation of tebapivat development for lower-risk myelodysplastic syndromes (LR-MDS) after the drug failed to achieve its primary endpoint in a Phase 2b clinical trial. The decision marks a significant setback for Agios, which had been exploring tebapivat as a potential treatment option for patients with this challenging blood disorder.
The outcome reflects the difficult nature of clinical drug development, where promising early-stage results do not always translate into success in larger studies. Despite the disappointment, Agios remains committed to advancing its broader hematology and rare disease pipeline.
Details of the Phase 2b Clinical Trial
The Phase 2b study conducted by Agios evaluated tebapivat in patients diagnosed with LR-MDS. Researchers aimed to determine whether the therapy could produce meaningful clinical benefits and improve key patient outcomes. While the drug demonstrated an acceptable safety profile, Agios reported that the study did not meet its predefined primary endpoint.
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