Agios Pharmaceuticals experienced a significant stock decline following the release of Phase 3 clinical trial data for its anemia medication Pyrukynd on Wednesday, November 19, 2025. The experimental treatment showed partial success in treating sickle cell disease, achieving one primary endpoint while falling short on another critical measure.
The drug, scientifically referred to as mitapivat, successfully met its objective of increasing healthy hemoglobin levels in patients. However, it failed to demonstrate a statistically significant reduction in painful vascular blockage episodes compared to placebo recipients. Despite these mixed outcomes, Agios announced plans to pursue discussions with U.S. regulatory authorities regarding a potential approval submission.
The company’s stock price experienced dramatic volatility in Wednesday morning trading, plummeting from approximately $45 per share to around $24, representing nearly a 50% decline. This setback comes as Agios awaits a Food and Drug Administration decision on the same drug for an alternative blood disorder indication. The regulatory agency postponed its verdict in September, with a new expected determination date of December 7.
The sickle cell disease therapeutic market has experienced considerable turbulence in recent years. Hydroxyurea, a longstanding treatment option, gained additional competition in 2019 when Novartis introduced Adakveo and Pfizer launched Oxbryta. Gene-based therapies from Vertex Pharmaceuticals and Bluebird Bio entered the market subsequently. However, European authorities later revoked Adakveo’s marketing permission, and Pfizer discontinued Oxbryta in 2024 despite investing over $5 billion to acquire the medication.
The genetic treatment approaches have also encountered commercial challenges. Through the end of September, Vertex reported that only 165 individuals had undergone initial cell collection procedures for Casgevy, its gene therapy product. Prior to its privatization, Bluebird recorded merely $11 million in 2024 revenue for its therapy, which carries a $3.1 million price tag.
These market disruptions have created potential openings for alternative treatments like mitapivat. Currently marketed as Pyrukynd for treating a rare anemia variant, mitapivat activates pyruvate kinase, an enzyme that supports red blood cell longevity. This mechanism positions it as a potentially valuable option for conditions including sickle cell disease and beta thalassemia. Additional approvals could substantially benefit Agios, considering the drug generated only approximately $22 million in revenue during the initial nine-month period of the current year.
The company may secure beta thalassemia approval within the coming month. However, obtaining sickle cell disease clearance depends on how regulatory officials interpret Wednesday’s disclosed study findings.
The Rise Up trial enrolled 207 sickle cell disease patients, with two-thirds randomly assigned to receive Pyrukynd and the remainder given placebo treatment.
Regarding the successfully achieved primary endpoint, 41% of Pyrukynd recipients experienced at least a 1 gram per deciliter increase in hemoglobin levels, compared to just 3% of placebo participants. Agios reported that responders demonstrated an average hemoglobin improvement of approximately 1.6 grams per deciliter.
However, the annual rate of sickle cell pain crises showed no statistically meaningful difference between groups. Pyrukynd recipients experienced roughly 2.6 such episodes annually, while placebo recipients had about 3.1 crises per year.
Trial investigator Biree Andemariam, a medical professor at the University of Connecticut Health, stated in an Agios-provided statement that Rise Up data confirms mitapivat significantly enhanced hemoglobin levels and decreased hemolysis. Additionally, patients meeting the hemoglobin response threshold experienced clinically meaningful improvements in pain crisis rates, related hospitalizations, and fatigue levels.
Should the FDA agree to evaluate a sickle cell disease application for mitapivat, regulators may need to weigh the mixed efficacy results against emerging safety considerations. The agency extended its beta thalassemia review timeline to examine a protocol addressing potential liver cell damage or inflammation observed during that disease’s testing.
While announcing sickle cell results, Agios noted that liver abnormalities observed in study participants did not suggest drug-induced hepatocellular injury.