Patient enrollment has been completed for the Phase 3 RISE UP study, a clinical trial assessing the safety and efficacy of the oral therapy mitapivat in individuals with sickle cell disease (SCD). Agios Pharmaceuticals, the developer of mitapivat and sponsor of the trial, announced that over 200 patients, aged 16 and older, have been enrolled. Results from the study are expected by the end of 2025.
Sarah Gheuens, MD, PhD, chief medical officer and head of research and development at Agios, expressed gratitude to the patients, study investigators, and patient advocates for their support in completing the enrollment. The company anticipates sharing topline results with the community in late 2025.
Mechanism of Action of Mitapivat in SCD
Sickle cell disease is caused by mutations leading to the production of abnormal hemoglobin, the protein responsible for oxygen transport in red blood cells. This faulty hemoglobin forms clumps, deforming red blood cells into a sickle shape, leading to premature breakdown and blood vessel blockage, causing pain and other symptoms.
Mitapivat, marketed as Pyrukynd for pyruvate kinase deficiency, enhances energy production in red blood cells by activating the pyruvate kinase enzyme. This activation is expected to maintain red blood cell integrity and function in SCD. Additionally, mitapivat reduces levels of 2,3-diphosphoglycerate (2,3-DPG), a molecule that promotes hemoglobin deoxygenation, thereby preventing hemoglobin clumping and red blood cell sickling.
RISE UP Trial Design and Objectives
The RISE UP trial (NCT05031780) was initiated to evaluate the safety and efficacy of mitapivat in SCD patients. The trial consists of a Phase 2 and a Phase 3 study, each enrolling distinct patient cohorts. Phase 2 dose-finding study results from 79 patients indicated that mitapivat, at doses of 50 or 100 mg twice daily, could increase hemoglobin levels compared to placebo over approximately three months. Both doses also reduced the annualized rate of pain crises.
In the Phase 3 study, participants are randomized to receive either mitapivat at 100 mg twice daily or a matching placebo for about one year. The primary objectives of the study are to determine the therapy’s effectiveness in increasing hemoglobin levels and reducing the rate of pain crises. Patients completing either the Phase 2 or Phase 3 study have the option to enroll in an open-label extension phase, where they will continue to receive mitapivat for up to 216 weeks (approximately four years).
