Phase 3 RISE UP study of mitapivat for SCD completes enrollment
Trial results from more than 200 patients expected by end of 2025
Patient enrollment has been completed for the Phase 3 RISE UP study, a clinical trial that’s assessing the safety and efficacy of the oral therapy mitapivat in people with sickle cell disease (SCD).
More than 200 patients, 16 and older, have been enrolled, and results from the study are expected toward the end of 2025, according to Agios Pharmaceuticals, the company developing mitapivat and sponsoring the trial.
“We sincerely thank the patients, study investigators and patient advocates for their instrumental support and partnership in helping us complete enrollment of the Phase 3 RISE UP study,” Sarah Gheuens, MD, PhD, chief medical officer and head of research and development at Agios, said in a company press release. “With enrollment now complete, we look forward to completing the trial and sharing topline results with the community in late 2025.”
SCD is caused by mutations that lead to the production of an abnormal form of hemoglobin, which is the protein that red blood cells use to carry oxygen through the body. The faulty hemoglobin tends to form clumps inside red blood cells, deforming the normally-rounded cells into a spiky sickle-like shape that gives the disease its name. The deformed red blood cells tend to break down prematurely and are prone to get trapped inside blood vessels, blocking blood flow and causing pain and other symptoms.
Mitapivat approved under name Pyrukynd for pyruvate kinase deficiency
Mitapivat is approved under the name Pyrukynd to treat a genetic disorder called pyruvate kinase deficiency that causes red blood cells to die prematurely. It’s designed to boost energy production in red blood cells by activating an enzyme called pyruvate kinase. Lack of energy can prompt red blood cells to lose their integrity and die prematurely in SCD. Thus, by activating pyruvate kinase, mitapivat is expected to help keep red blood cells healthy and functional.
Another consequence of activating pyruvate kinase that’s beneficial in SCD is the reduction in the levels of 2,3-diphosphoglycerate (2,3-DPG), a molecule that promotes hemoglobin deoxygenation, which is the state the protein must be in to clump up inside red blood cells. By lowering 2,3-DPG levels, mitapivat is expected to prevent hemoglobin clumping and red blood cell sickling.
The RISE UP trial (NCT05031780) was launched in late 2021 to explore the safety and efficacy of mitapivat in people with SCD. The trial includes a Phase 2 and a Phase 3 study enrolling different patients.
Results from 79 patients who took part in the Phase 2 dose-finding study, announced late last year, indicated the two tested doses of mitapivat (50 or 100 mg taken twice daily) could boost hemoglobin levels compared with a placebo over the course of about three months. Both doses also led to reductions in the annualized rate of pain crises.
In the Phase 3 study, participants will be randomly assigned to take mitapivat at a dose of 100 mg twice daily, or a matching placebo for about one year. The study’s main goals are to assess the therapy’s ability to increase hemoglobin levels and to reduce the rate of pain crises.
Patients who complete the Phase 2 or the Phase 3 study will have the chance to enroll in an open-label extension phase, where they will continue receiving mitapivat for up to 216 weeks, or about four years.
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