Agios Pharmaceuticals has abandoned an indication for its next-generation activator of pyruvate kinase (PK) in sickle cell disease (SCD) – the second indication the company has dropped in two months.
In phase 2, 59 patients with SCD were randomized to receive daily oral tebapivat at three different doses or placebo. Tebapivat, like Agios’ FDA-approved hemolytic anemia drug Pyrukynd, targets one of the enzymes involved in glucose metabolism, increasing its levels. The evidence for the effect of enzyme activation on reducing the sickling of red blood cells has been a stimulus to the development of PK activators in SCD.
Data from Pyrukynd is conflicting but the drug has not yet been approved by the FDA in the indication, whereas Novo Nordisk’s etavopivat had confirmed efficacy in a phase 3 study in the indication. Agios, however, hoped that structural changes that would allow for once-daily dosing without having to taper the dose would set tebapivat apart.
Agios lost the bet. The biotech company gave up on developing tebapivat for lower-risk myelodysplastic syndromes (LR-MDS) two months ago, and has now dropped its plans to launch the candidate in SCD. As happened in LR-MDS, underwhelming phase 2 data torpedoed Agios’ hopes of developing tebapivat in SCD.
For the three tebapivat dose groups, 33.3% of the placebo patients met the trial’s primary endpoint of hemoglobin response, compared to 29.4% to 47.1% of the patients in each dose group. 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 shifted Pyrukynd into a key SCD developmental stage with a hemoglobin response seen in 46.2-50% of patients treated with the twice-daily therapy in a phase 2 clinical trial, from Weeks 10 through 12. In a 12-week phase 1 study, Novo Nordisk reported a 73% response rate for etavopivat, which led to research and a recent 48.7% response rate for the once-daily therapy after 24 weeks in a phase 3 study.
The phase 2 trial, however, “did not meet our expectations for level of differentiation that would support continued development,” said Sarah Gheuens, Agios chief medical officer and head of R&D, 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 has announced the discontinuation of its investigational sickle cell disease program after Phase 2 clinical trial results failed to meet expectations. The decision reflects the company’s commitment to allocating research and development resources toward programs with stronger clinical potential. While disappointing, portfolio adjustments are a common part of pharmaceutical development and allow companies to focus on the most promising therapeutic candidates.
Agios Discontinues Sickle Cell Development Program
The Phase 2 study evaluated an experimental treatment intended to improve outcomes for patients living with sickle cell disease. According to Agios, the clinical data did not demonstrate the level of efficacy required to justify further development. As a result, the company has decided to end the program and redirect its investments toward other pipeline opportunities.
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