Benzinga | Nov 12, 2020 04:37PM EST

Agios Announces FDA Orphan Drug Designation Granted to Mitapivat for Treatment of Sickle Cell Disease

Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to the company's first-in-class pyruvate kinase R (PKR) activator mitapivat for the treatment of patients with sickle cell disease. Mitapivat is an investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated PKR enzymes.



"Receiving orphan drug designation for mitapivat in sickle cell disease is an important recognition of the tremendous unmet need among this patient community, which has historically been underserved," said Chris Bowden, M.D., chief medical officer at Agios. "As the pioneers in PKR activation, we believe this mechanism has the potential to transform the course of sickle cell disease and are researching mitapivat's ability to improve red blood cell energy, health and longevity. We look forward to continued partnership with the sickle cell disease community and expect to initiate our Phase 3 study next year."

The FDA's Office of Orphan Drug Products grants orphan status to support the development of medicines for rare disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

Mitapivat was previously granted orphan drug designation by the FDA and the European Medicines Agency for the treatment of pyruvate kinase (PK) deficiency, a rare, debilitating, hemolytic anemia, and by the FDA for the treatment of thalassemia.

Mitapivat Clinical Development

Mitapivat is being evaluated as a potential treatment for sickle cell disease under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health. Mitapivat has been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and increase adenosine triphosphate (ATP), and through this mechanism, it may reduce hemoglobin S polymerization and red blood cell sickling. Preliminary clinical data establishing proof-of-concept for mitapivat in sickle cell disease were disclosed in June 2020, and updated data from this trial will be presented at the American Society of Hematology (ASH) Annual Meeting, which is being held virtually December 5--8, 2020. Agios expects to initiate a Phase 3, global, pivotal study of mitapivat in sickle cell disease in 2021.

In addition, Agios has two ongoing global, pivotal trials in adults with PK deficiency that are fully enrolled.

* ACTIVATE: A placebo-controlled trial with a 1:1 randomization evaluating mitapivat in patients who do not receive regular transfusions. The primary endpoint of the trial is hemoglobin response, defined as a sustained hemoglobin increase of ?1.5 g/dL from baseline. Agios anticipates reporting ACTIVATE topline data by the end of 2020.

* ACTIVATE-T: A single arm trial evaluating mitapivat in patients who receive regular transfusions. The primary endpoint of the trial is the proportion of patients who achieve a reduction in transfusion burden compared to individual historical transfusion burden standardized to 24 weeks. Agios anticipates reporting topline ACTIVATE-T data in Q1 2021.

Agios is also conducting a Phase 2 study evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of treatment with mitapivat in adults with non-transfusion-dependent ?- or ?-thalassemia. The trial is fully enrolled, and the primary endpoint is hemoglobin response, defined as a ?1.0 g/dL increase in Hb concentration from baseline. Agios expects to initiate a Phase 3 pivotal program evaluating mitapivat in thalassemia, including both ?-and ?-thalassemia, as well as transfusion dependent and non-transfusion dependent patient populations, in 2021.

Mitapivat is not approved for use by any regulatory authority.