Top-line data from Phase 3 trial of mitapivat expected this year
Agios' SCD treatment, if approved, could hit US market in 2026
Top-line data from the Phase 3 part of RISE UP, a clinical trial testing mitapivat in people with sickle cell disease (SCD), are expected by the end of the year, according to developer Agios Pharmaceuticals.
If those results are positive and mitapivat wins regulatory approval for SCD, it may be launched in the U.S. market in 2026, per a company press release that outlined Agios’ first-quarter financial results.
“Looking ahead, our focus is also on delivering the top-line results from the Phase 3 RISE UP study in sickle cell disease, which remains on track for year-end, and continuing to advance our early and [midstage] clinical programs,” said Brian Goff, Agios’ CEO.
The company also plans to launch a Phase 2 trial testing another treatment candidate, tebapivat, in people with SCD. The tebapivat trial is expected to start by the middle of next year, per the developer. Both mitapivat and tebapivat are designed to activate the pyruvate kinase (PK) enzyme in red blood cells to help improve their health.
Treatment aims to improve energy production in red blood cells
SCD is caused by the production of an abnormal version of hemoglobin, the protein responsible for carrying oxygen in red blood cells. This causes red blood cells to take on the sickle-like shape that gives the disease its name.
These sickled cells are prone to die prematurely and tend to stick to each other and to blood vessel walls, blocking blood and impairing oxygen delivery to tissues. Blood vessel blockage, in turn, can lead to a series of complications, including pain crises.
Mitapivat is designed to activate PK in red blood cells, with the goal of improving energy production in these cells. It also aims to help lower the levels of 2,3-diphosphoglycerate (2,3-DPG), a molecule found at high levels in SCD patients.
Lack of energy may cause red blood cells to lose their integrity and die. 2,3-DPG reduces hemoglobin’s affinity for oxygen and promotes red blood cell sickling. By reversing both effects, the therapy is expected to help keep red blood cells healthy and functional, thereby easing SCD symptoms.
The therapy’s safety and efficacy in SCD are being evaluated in the Phase 2/3 RISE UP trial (NCT05031780), which launched in 2022.
In the trial’s Phase 2 part, patients were randomly assigned to receive either 50 mg or 100 mg of mitapivat, or a placebo, twice daily for 12 weeks. Results from the Phase 2 part of the trial, which enrolled 79 SCD patients, showed mitapivat was able to increase hemoglobin levels and lower the annual rate of pain crises when compared with a placebo.
In the study’s Phase 3 part, more than 200 SCD patients are receiving mitapivat at a dose of 100 mg, or a placebo, twice daily for 52 weeks. The main goal of this part of the study, which completed patient enrollment last year, is to assess mitapivat’s ability to increase hemoglobin levels and reduce the rate of pain crises.
Participants who complete either the Phase 2 or the Phase 3 part of the study may continue on in its extension period, during which they will receive mitapivat for 216 weeks, or about four years.
Mitipavit earns orphan drug status in EU
Earlier this year, mitapivat was granted orphan drug status in the European Union for SCD. The designation is meant to incentivize the development of therapies for rare diseases, or those affecting fewer than five in 10,000 people in the EU. Orphan status has several benefits, including exemptions from certain fees and 10 years of market exclusivity upon approval.
Mitapivat is approved under the name Pyrukynd to treat adults with pyruvate kinase deficiency, another genetic condition that causes red blood cells to die early. The therapy is also under review in the U.S. for approval to treat thalassemia, another bleeding disorder, with a decision expected in September.
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