RARE Daily

Agios’ Mitapivat Meets Primary Endpoint in Late-Stage Study in Pyruvate Kinase Deficiency

January 27, 2021

Rare Daily Staff

Agios Pharmaceuticals said that the global, open-label phase 3 ACTIVATE-T trial of mitapivat in regularly transfused adults with PK deficiency, which causes a chronic form of anemia, demonstrated a statistically significant and clinically meaningful reduction in transfusion burden.

Pyruvate kinase (PK) deficiency is a rare, inherited disease that presents as chronic hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutations in PKR genes cause a deficit in cellular energy within the red blood cell and a build-up of metabolites. PK deficiency is associated with serious complications, including gallstones, pulmonary hypertension, extramedullary hematopoiesis, osteoporosis and iron overload. PK deficiency can also cause quality of life problems, including challenges with work and school activities, social life and emotional health.

Current management strategies for PK deficiency, including red blood cell transfusions and splenectomy, are associated with both short- and long-term risks. There are no currently approved therapies for PK deficiency.

Mitapivat is a first-in-class, experimental, oral, small molecule allosteric activator of wild-type and a variety of mutated PKR enzymes.

All 27 patients enrolled in the study were treated with mitapivat. In the 24-week fixed dose period, 37 percent achieved a 33 percent or greater reduction in transfusion burden compared to individual historical transfusion burden standardized to 24 weeks. In addition, 22 percent were transfusion-free during the 24-week fixed dose period.

The results follow the recent release of results from Agios’ phase 3 ACTIVATE trial of mitapivat in adults with PK deficiency who do not receive regular transfusions, which met its primary endpoint with 40 percent of patients randomized to mitapivat achieving a sustained increase in hemoglobin concentration from baseline.

“The ACTIVATE-T study represents our first study of mitapivat in regularly transfused patients, and when taken together with the ACTIVATE results, demonstrates mitapivat’s potential clinical benefit for patients regardless of transfusion burden,” said Chris Bowden, chief medical officer at Agios.

The safety profile observed in the study was consistent with previously reported data.

Agios anticipates filing for regulatory approval based on data from ACTIVATE and ACTIVATE-T in the United States in the second quarter of 2021 and in the European Union in mid-2021, with a potential 2022 commercial launch in both geographies.

Photo: Chris Bowden, chief medical officer at Agios


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