Potential first-in-class treatment for SCD awarded FDA priority review
'Global' trial expected to launch next month to confirm drug's effectiveness
Written by |
The U.S. Food and Drug Administration (FDA) has granted priority review — a decision that could speed a drug’s approval — to an application for the oral therapy mitapivat for sickle cell disease (SCD).
According to developer Agios Pharmaceuticals, mitapivat, if approved, will be the first therapy of its class for people with SCD in the U.S.
Priority review means the FDA will expedite its regulatory evaluation, completing it in six months instead of the usual 10. A final decision on whether or not to clear mitapivat for use in SCD is now expected by Nov. 1, the developer noted in a company press release.
“The Priority Review designation for the mitapivat [application] marks an important milestone for the sickle cell community — a large, underserved population that has long needed new treatment options to help manage the significant burden of disease,” said Sarah Gheuens, MD, PhD, Agios’ chief medical officer and head of research and development. “Mitapivat is well positioned to address this treatment gap.”
Agios submitted its application earlier this year under the FDA’s accelerated approval pathway, which allows medicines addressing a serious medical need to be approved based on preliminary safety and effectiveness data from clinical trials. Under an agreement with the FDA, this pathway would generally require that a confirmatory clinical trial be underway at the time of regulatory clearance to confirm mitapivat’s benefit for people with SCD. Full approval will be dependent on those results.
Called REIGNITE (NCT07656415), the confirmatory, placebo-controlled Phase 3 trial is set to start in August, per the company. It will enroll an estimated 159 SCD patients, ages 12 and older, and will be “global,” according to Agios. However, no details on the location of trial sites have been provided.
A rare inherited blood disorder, SCD causes hemoglobin — the protein responsible for carrying oxygen in red blood cells — to assume an abnormal shape that makes red blood cells stiff and crescent-shaped. These sickled cells break down more quickly than normal and can also clog blood vessels, producing painful episodes referred to as vaso-occlusive crises.
Mitapivat targets an enzyme called pyruvate kinase, or PK, that plays a role in how red blood cells generate energy. By activating this enzyme, the drug also lowers levels of a compound called 2,3-DPG, which tends to increase in SCD and contribute to the sickling process.
The therapy already carries U.S. approval under two brand names for distinct diseases: Pyrukynd, for hemolytic anemia in adults with PK deficiency, and Aqvesme, for anemia in adults with thalassemia, another blood disorder.
For SCD, mitapivat has been awarded orphan drug status in both the U.S. and the European Union. That designation is intended to support development of treatments for rare conditions, such as SCD, through benefits that include fee waivers and, if the drug is ultimately approved, periods of market exclusivity.
Approval for mitapivat sought based on clinical testing results
Gheuens noted that the company’s application for mitapivat for SCD was “supported by results from the RISE UP clinical program and a foundational dataset spanning more than a decade of research.” That work “includes over 1,300 patient-years of clinical experience across multiple hemolytic anemias,” Gheuens added.
Patient-years is a measure calculated by multiplying the number of patients followed in a clinical study by the total time each was observed. Hemolytic anemias, including SCD, are conditions marked by low red blood cell counts, or anemia, which is due to the cells’ premature destruction in a process called hemolysis.
The evidence behind the mitapivat filing for SCD comes from the placebo-controlled Phase 2/3 RISE UP trial (NCT05031780), which involved 286 adolescents and adults with SCD. All of the participants had low hemoglobin and a history of 2-10 pain crises in the year before enrollment.
The study’s Phase 2 portion showed that twice-daily mitapivat significantly increased hemoglobin levels and reduced pain crises compared with the placebo. In its Phase 3 portion, more mitapivat-treated patients saw their hemoglobin rise between the six-month and one-year marks than did those on the placebo.
Developer says it will work with FDA throughout review
Meaningful drops in pain crises, hospital stays, and fatigue were also observed among those with a hemoglobin response on mitapivat treatment. The therapy’s safety profile was consistent with that reported in previous studies.
Participants completing either phase of the trial could enter the open-label extension portion, in which all are receiving mitapivat for up to four years.
In the upcoming confirmatory REIGNITE study, participants will be randomly assigned to receive either mitapivat or a placebo twice daily for 52 weeks, or one year.
The trial’s main goal is to measure the proportion of patients who are free of blood transfusions between weeks four and 52. Secondary measures include the proportion of participants experiencing a pain crisis and the number of red blood cell units transfused. Changes in hemoglobin and other hemolysis markers will also be assessed.
Those completing REIGNITE’s placebo-controlled portion may enter its open-label extension, during which all will receive the oral therapy.
“We look forward to working collaboratively with the FDA throughout this review, with the goal of delivering the first oral PK activator in sickle cell disease,” Gheuens said.
Leave a comment
Fill in the required fields to post. Your email address will not be published.