Agios Pharmaceuticals (NASDAQ:AGIO) used an investor webcast tied to the 2026 European Hematology Association Congress in Stockholm to highlight new clinical data for mitapivat across thalassemia and sickle cell disease, while outlining a broader rare disease strategy that now includes multiple hematology and metabolic programs.
Chief Executive Officer Brian Goff said Agios is moving from “a single asset story to a multi-asset, multi-indication platform,” citing mitapivat, next-generation PK activator tevapivat, and newer programs in polycythemia vera, immune thrombocytopenia and phenylketonuria. Goff said the company is focused on rare diseases where biology is well understood and treatment options remain limited.
Thalassemia Data Support Durability of AQVESME
According to Gheuens, patients who continued mitapivat from the double-blind period into the extension saw the mean duration of hemoglobin response more than double, from 17.9 weeks to 43.6 weeks at the data cutoff, with responses still ongoing. Nearly 60% of patients continuing mitapivat achieved a hemoglobin response, defined as at least a 1 gram per deciliter improvement from baseline in average hemoglobin over two consecutive visits in the extension period.
Gheuens said approximately one-third of prior non-responders during the double-blind period achieved a hemoglobin response in the extension period, and patients switching from placebo to mitapivat showed improvements consistent with those seen earlier in the study. The mean change from baseline in hemoglobin across the extension data was 1.3 grams per deciliter. She said no new safety events changed the company’s understanding of mitapivat’s safety profile in thalassemia.
Agios also presented a post-hoc analysis of ENERGIZE patients with higher baseline hemoglobin levels of at least 9.5 grams per deciliter. In that group, 38.9% achieved a hemoglobin increase of at least 1 gram per deciliter, alongside a 5.1-point improvement in FACIT fatigue scores from week 12 to week 24.
Chief Commercial Officer Tsveta Milanova said AQVESME has had 242 prescriptions written as of March 31 by REMS-certified physicians. She said early demand has been supported by REMS onboarding and shorter-than-expected time to treatment, though the company continues to plan for an average 10- to 12-week initiation timeline.
RISE UP Shows Hemoglobin Response in Sickle Cell Disease, Misses Pain Endpoint
Agios also highlighted the phase 3 RISE UP trial of mitapivat in sickle cell disease. The global randomized, placebo-controlled study enrolled 207 patients aged 16 years or older and randomized them 2-to-1 to mitapivat or placebo over a 52-week double-blind period.
Gheuens said mitapivat demonstrated a 40.6% hemoglobin response compared with 2.9% on placebo, with responses maintained through week 62. Among responders, the mean hemoglobin increase was 1.6 grams per deciliter. The company also reported rapid and durable improvements in hemoglobin and indirect bilirubin.
However, Gheuens said the trial did not achieve statistical significance on its other primary endpoint, the annualized rate of sickle cell pain crisis, or on the key secondary endpoint of change from baseline in PROMIS fatigue. She said directional responses favored mitapivat across measures of hemolysis and other pain crisis-related endpoints.
In hemoglobin responders, Agios reported reductions in several disease-related outcomes compared with non-responders, including:
- A 26% reduction in annualized rate of pain crisis;
- 34% fewer hospitalizations;
- A 53% reduction in annualized rate of emergency room visits for sickle cell pain crisis;
- A 37% reduction in annualized rate of hospitalization days for sickle cell pain crisis.
Agios also reported that mitapivat reduced the proportion of patients requiring transfusions by 41% and the number of units transfused by 66% relative to placebo in the total RISE UP population. Gheuens said these findings informed the design of REIGNITE, a confirmatory phase 3 trial under the U.S. Accelerated Approval Pathway.
Physicians Discuss Sickle Cell Burden and Transfusion Reduction
During a fireside chat moderated by Agios Senior Medical Director Dr. Ahmar Zaidi, Dr. Alan Anderson of Prisma Health and the University of South Carolina School of Medicine Greenville said adults with sickle cell disease continue to face limited disease-modifying options and cumulative organ damage over time.
Dr. Kenneth Ataga of the University of Tennessee Health Science Center said sickle cell disease is heterogeneous and that progressive organ dysfunction increases mortality risk as patients age. Both physicians emphasized the role of chronic anemia and hemolysis in fatigue, organ damage and other complications.
Asked about transfusion burden, Ataga said repeated transfusions can create risks including iron overload and red blood cell alloimmunization, which can make future transfusions more difficult. Anderson added that reducing transfusions can reduce clinic visits and improve quality of life for patients.
Confirmatory Trial and Sickle Cell Launch Planning
The REIGNITE trial is designed as a 62-week global, double-blind, randomized study evaluating transfusion independence from week 4 through week 62 as its primary endpoint. Agios said the study will enroll patients aged 12 and older, potentially supporting a broader future label than RISE UP, which studied patients 16 and older.
Milanova said there are approximately 75,000 diagnosed sickle cell patients aged 16 and older in the U.S., including roughly 25,000 who are actively treated or in need of therapy. She said Agios’ initial launch focus would be patients with a hemolytic profile and a known prescriber base.
In the Q&A session, Gheuens said the initial sickle cell label, if approved, would reflect the RISE UP data package, while future confirmatory trial results could be added later. She also said Agios has filed its supplemental new drug application for mitapivat in sickle cell disease and continues to engage with the FDA.
Pipeline Updates Include AG-236, Cevidoplenib and Tevapivat
Goff said Agios will advance AG-236 into late-stage development for polycythemia vera after completing a phase 1 healthy volunteer study. He said the data showed dose-dependent hepcidin induction, sustained pharmacodynamic activity and favorable tolerability. Gheuens said the company sees potential for dosing as infrequently as every six months.
Goff also highlighted cevidoplenib, a next-generation SYK inhibitor for immune thrombocytopenia, which he said represents a potential $1 billion non-risk-adjusted peak-year U.S. sales opportunity. He said Agios plans to update investors as the program moves toward phase 3 initiation.
The company also expects phase 2 top-line data for tevapivat in sickle cell disease in the coming months and phase 1 proof-of-mechanism data for AG-181 in phenylketonuria patients before year-end. Goff said the company’s pipeline represents potential markets totaling more than $10 billion in 2030.
About Agios Pharmaceuticals (NASDAQ:AGIO)
Agios Pharmaceuticals, Inc is a biopharmaceutical company founded in 2008 as a spin-out from research at Dana-Farber Cancer Institute and the Broad Institute. Headquartered in Cambridge, Massachusetts, Agios focuses on understanding and targeting cellular metabolism to develop novel therapies for cancer and rare genetic diseases. The company’s scientific platform integrates genomic discovery, metabolic profiling and precision medicine approaches to identify and advance small-molecule candidates that correct or exploit metabolic dysfunction.
Agios’s lead products are IDH (isocitrate dehydrogenase) inhibitors that target specific cancer mutations.
