Agios readies FDA filing as anemia drug clears another phase 3

A second phase 3 trial of Agios Pharmaceuticals’ mitapivat has hit its primary endpoint in patients with pyruvate kinase deficiency, keeping the biotech on track to file for approval on both sides of the Atlantic in the coming months.

The latest clinical readout comes from a single-arm study that gave the oral, small-molecule allosteric activator of pyruvate kinase-R enzymes to 27 regularly transfused patients with PK deficiency. Agios compared the performance of the patients during the 24-week fixed dose period—which followed 16 weeks of dose optimization—to historical data to show the effect of mitapivat on transfusion burden.

Ten patients experienced a 33% or greater drop in transfusion burden during the fixed-dose period. Agios used individual historical transfusion burden standardized to 24 weeks to generate a one-sided p-value of 0.0002. Six patients were transfusion-free during the fixed dose period.

That is the extent of the data shared by Agios to date. The biotech spoke in broad terms about other aspects of the results, stating the trial linked mitapivat to a reduction in the annualized total number of red blood cell units transfused versus a historical control. On safety, Agios only said the profile “was consistent with previously reported data.”

A full breakdown of the data is still months away. Agios plans to share data from the single-arm trial, plus the results of a larger, randomized study that read out last month, at the European Hematology Association Virtual Congress in June.

By then, Agios expects to have advanced its efforts to get mitapivat to market. A filing for approval in the U.S. is planned for the second quarter, with a European submission set to follow around the midpoint of the year. 

The available data suggest mitapivat increases hemoglobin concentration in a significant minority of PK deficiency patients who don’t regularly receive transfusions and reduces transfusion burden in their counterparts who do regularly receive blood. However, the limited top-line releases leave some questions about the safety and efficacy of mitapivat unanswered. Safety is a particular concern in light of adverse events including a vaso-occlusive crisis in an earlier sickle cell disease study.

Winning approval in PK deficiency would unlock a relatively small commercial opportunity for Agios. To turn mitapivat into a blockbuster, Agios will likely need to establish the drug as an effective sickle cell disease treatment, a more competitive indication in which it still needs to prove itself.