The European Commission has adopted a positive decision, granting orphan medicinal product (OMP) designation to Agios Pharmaceuticals' mitapivat for the treatment of sickle cell disease. This designation aims to encourage the development of innovative therapies for life-threatening or chronically debilitating conditions affecting fewer than five in 10,000 individuals in the European Union.
Orphan Drug Designation Benefits
The OMP designation provides several benefits, including reduced fees and a 10-year period of market exclusivity, intended to incentivize the development of medicines for rare diseases. Mitapivat, an oral, small molecule pyruvate kinase (PK) activator, had previously received orphan drug designation from the U.S. Food and Drug Administration (FDA) in November 2020 for the same indication.
RISE UP Study Details
The efficacy and safety of mitapivat in sickle cell disease are currently being evaluated in the Phase 2/3 RISE UP study. This study includes patients aged 16 years or older who have experienced between two and 10 sickle cell pain crises in the past 12 months and have hemoglobin levels within the range of 5.5 to 10.5 g/dL during screening. The Phase 2 study included a 12-week randomized, placebo-controlled period. The primary endpoint was hemoglobin response, defined as ≥1.0 g/dL increase in average hemoglobin concentration from Week 10 through Week 12 compared to baseline, and safety. Agios presented positive results from the Phase 2 study at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023.
The Phase 3 study is a 52-week randomized, placebo-controlled trial where participants are randomized in a 2:1 ratio to receive 100 mg of mitapivat twice daily or a matched placebo. The primary endpoints include hemoglobin response, defined as a ≥1.0 g/dL increase in average hemoglobin concentration from Week 24 through Week 52 compared with baseline, and the annualized rate of sickle cell pain crises. Enrollment in the Phase 3 study has been completed, with over 200 patients enrolled worldwide.
Mitapivat's Potential Impact
Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios, stated, "Alongside the FDA’s orphan drug designation in the U.S., the European Commission’s orphan medicinal product designation for mitapivat underscores the urgent need for novel therapies for sickle cell disease and highlights its potential to provide clinically meaningful benefits to patients navigating this debilitating condition." The company anticipates sharing the results of the Phase 3 RISE UP study in late 2025.
About Mitapivat (PYRUKYND®)
Mitapivat, marketed as PYRUKYND®, is a pyruvate kinase activator already approved for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States and for the treatment of PK deficiency in adult patients in the European Union. It is crucial to avoid abruptly discontinuing PYRUKYND® due to the risk of acute hemolysis and anemia. Gradual tapering is recommended, with monitoring for signs of hemolysis and anemia during discontinuation.
