EU Approves Orphan Drug Status for Agios' Mitapivat in Sickle Cell Disease

Agios Pharmaceuticals, Inc., a leader in the field of cellular metabolism and pyruvate kinase activation, has achieved a significant milestone with the European Commission's positive decision to designate mitapivat as an orphan medicinal product for sickle cell disease. Mitapivat, an oral small molecule pyruvate kinase activator, had previously received orphan drug designation from the U.S. Food and Drug Administration in November 2020 for the same condition. This dual recognition underscores the potential of mitapivat to offer meaningful clinical benefits to individuals suffering from this debilitating disease.

Dr. Sarah Gheuens, Agios' chief medical officer, emphasized the importance of these designations in highlighting the urgent need for innovative therapies for sickle cell disease. The company is eagerly anticipating the results of their fully enrolled Phase 3 RISE UP study, which focuses on the safety and efficacy of mitapivat, and plans to share these findings with the community by late 2025.

The European Commission grants orphan medicinal product designation to treatments addressing life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 people within the European Union. This designation offers significant developmental incentives, including reduced fees and a decade of market exclusivity, providing a strong foundation for the advancement of such therapies.

The RISE UP Phase 2/3 study investigates mitapivat's effectiveness and safety in patients aged 16 and older who have experienced two to ten sickle cell pain crises in the past year, with hemoglobin levels between 5.5 and 10.5 g/dL during screening. The study is streamlined through a seamless Phase 2/3 protocol, optimizing resources by using the same sites and vendors.

The Phase 2 component involved a 12-week, randomized, placebo-controlled trial where participants received either 50 mg or 100 mg of mitapivat twice daily, or a placebo. Primary endpoints included a hemoglobin response, defined as a rise of at least 1.0 g/dL in hemoglobin concentration from Week 10 to Week 12 compared to baseline, along with safety assessments. Positive outcomes from this phase were presented at the 65th American Society of Hematology Annual Meeting in December 2023.

Phase 3 extends over a 52-week period with participants assigned to 100 mg of mitapivat or a placebo, aiming to measure hemoglobin response from Week 24 to Week 52 and the frequency of sickle cell pain crises annually. As of October 2024, enrollment was completed with over 200 patients globally.

Participants completing the double-blind phase of either study can enter a 216-week open-label extension to receive mitapivat.

Mitapivat is marketed under the name PYRUKYND for treating hemolytic anemia in adults with pyruvate kinase deficiency in the United States and for similar conditions in adults within the European Union. However, abrupt discontinuation can lead to acute hemolysis and anemia, thus a gradual tapering of the dose is recommended upon discontinuation. Serious adverse reactions observed include atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain among others, according to the ACTIVATE trial.

Agios remains at the forefront of pyruvate kinase activation, focusing on providing transformative therapies for rare diseases. The company's expertise in classical hematology and cellular metabolism continues to drive its robust pipeline of investigational medicines targeting a range of hematologic conditions.