Mitapivat granted orphan drug status in EU for SCD
Oral therapy currently being tested in Phase 2/3 RISE UP trial
The European Commission has granted orphan medicinal product status to mitapivat, Agios Pharmaceuticals’ oral investigational therapy for sickle cell disease (SCD).
This designation is granted to treatments for rare diseases, or those affecting fewer than five in 10,000 people in the European Union, that have the potential to provide significant benefits over existing treatments. It also comes with incentives, including exemptions from certain fees and 10 years of market exclusivity if the therapy is ultimately approved.
Mitapivat had been named an orphan drug for SCD by the U.S. Food and Drug Administration (FDA) in 2020.
“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,” Sarah Gheuens, MD, PhD, Agios’ chief medical officer and head of research and development, said in a company press release.
SCD is caused by mutations that lead to the production of a faulty version of hemoglobin, the protein that red blood cells use to carry oxygen through the bloodstream. This defective form of the protein tends to clump inside cells when not bound to oxygen, making them acquire a sickle-like shape. The deformed red blood cells are more prone to break down prematurely and to get trapped inside blood vessels, blocking blood flow and causing pain and other disease symptoms.
Mitapivat designed to activate enzyme called pyruvate kinase in red blood cells
Mitapivat is designed to activate an enzyme called pyruvate kinase in red blood cells. By activating this enzyme, the therapy boosts energy production in red blood cells and helps lower the levels of 2,3 diphosphoglycerate (2,3-DPG). Lack of energy can cause red blood cells to lose their integrity and die prematurely, while 2,3-DPG, a molecule found at high levels in SCD patients, reduces hemoglobin’s affinity for oxygen and consequently promotes red blood cell sickling.
By counteracting both of these effects, mitapivat is expected to help red blood cells stay healthy and functional. It is approved under the name Pyrukynd to treat hemolytic anemia (when red blood cells break down faster than the body can replace them) in adults with pyruvate kinase deficiency, another genetic condition that causes red blood cells to die early.
The therapy’s safety and efficacy in people with SCD is currently being evaluated in the Phase 2/3 RISE UP trial (NCT05031780), which has recently completed patient enrollment.
Results from the Phase 2 part of the RISE UP trial, which enrolled 79 SCD patients, showed both mitapivat doses tested (50 and 100 mg, given twice daily for three months) increased hemoglobin levels and reduced the annualized rate of pain crises, compared with a placebo.
In the study’s Phase 3 part, more than 200 patients enrolled worldwide will receive either mitapivat at a dose of 100 mg or a placebo, twice daily, for about one year. The main goal is to assess the therapy’s efficacy in increasing hemoglobin levels and reducing the rate of pain crises.
Participants who complete either study parts may enroll in an open-label extension period, where all will receive the treatment for about four years.
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