Agios Pharmaceuticals’ next-gen pyruvate kinase (PK) activator has failed a phase 2 study in a group of rare blood cancers, although the biopharma is still holding out hope in sickle cell disease (SCD).
The company was evaluating various once-daily doses of the oral therapy, called tebapivat, in a 24-week trial of 65 patients with lower-risk myelodysplastic syndromes (LR-MDS). The phase 2b study missed its primary endpoint as measured by the number of patients who didn’t require a blood transfusion for eight consecutive weeks.
While Agios said tebapivat was well-tolerated and demonstrated “evidence of biological activity,” the lack of sufficient clinical benefit means the company won’t be pursuing the drug in this indication.
Things had been looking good for tebapivat as a potential LR-MDS treatment after data from the phase 2a portion of the program back in 2023 demonstrated a “meaningful reduction in transfusions.”
Despite this morning’s fail, the biopharma isn’t ready to give up on tebapivat completely. The drug is already undergoing a phase 2 study in SCD, with a readout pencilled in for the second half of the year, according to Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios.
“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,” Gheuens said in a May 29 release.
“PK activation remains a clinically validated mechanism, and we continue to see significant potential for tebapivat as a next-generation medicine in sickle cell disease,” she added.
Agios’ approved PK activator Pyrukynd has struggled against SCD, with mixed phase 3 results last year denting the company’s stock.
Pyrukynd won approval in 2022 as the first therapy indicated for hemolytic anemia in adults with PK deficiency. The company’s ambitions to grow beyond its existing patient population have so far faced ups and downs, with a study of Pyrukynd in children with PK deficiency who receive regular transfusions missing its prespecified statistical criterion in 2024.
However, Agios ended last year with some good news when the FDA approved the drug to treat anemia in adults with alpha- or beta-thalassemia under the brand name Aqvesme.
