RARE Daily

Agios Seek Approval for Mitapivat for Rare Inherited Blood Disorder

June 21, 2021

Agios Pharmaceuticals said it has submitted a New Drug Application for mitapivat to the U.S. Food and Drug Administration for the treatment of adults with pyruvate kinase deficiency.

Photo: Chris Bowden, chief medical officer at Agios

Pyruvate kinase (PK) deficiency presents as chronic hemolytic anemia, which is the accelerated destruction of red blood cells. Mutations in PKR genes cause a deficit in cellular energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate (ATP) levels, and result in a build-up of metabolites. PK deficiency is associated with serious complications, including gallstones, pulmonary hypertension, extramedullary hematopoiesis, osteoporosis, and iron overload, which can occur regardless of the degree of anemia or transfusion burden. PK deficiency can also cause quality of life problems, including challenges with work and school activities, social life and emotional health.

Mitapivat is an experimental, first-in-class, novel, oral activator of both wild-type (normal) and mutated pyruvate kinase-R (PKR) enzymes.

“With this NDA filing, we are poised to deliver the first potentially disease-modifying therapy for people with PK deficiency, a chronic, lifelong hemolytic anemia characterized by serious complications affecting multiple organs,” said Chris Bowden, chief medical officer at Agios. “There are no approved therapies for PK deficiency, and the current management strategies of blood transfusions and splenectomy are associated with both short- and long-term risks, including iron overload, blood clots and increased risk for infections.

Agios said it has also expanded the clinical application of mitapivat into thalassemia and sickle cell disease where it has the potential to provide therapeutic benefit by activating wild-type PKR. Based on preliminary clinical data, proof-of-concept has been established for mitapivat as a potential treatment for both of these hemolytic anemias.

The NDA submission is based on results from two pivotal studies, ACTIVATE and ACTIVATE-T, conducted in not regularly transfused and regularly transfused adults with PK deficiency, respectively. An extension study for adults with PK deficiency previously enrolled in ACTIVATE or ACTIVATE-T is ongoing and designed to evaluate the long-term safety, tolerability and efficacy of treatment with mitapivat.

The company said it remains on track to submit a marketing authorization application in the European Union in mid-2021 for mitapivat in adults with PK deficiency.

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