Agios Pharmaceuticals (NASDAQ:AGIO) hosted an investor conference call to discuss the FDA approval of mitapivat for the treatment of anemia in adults with alpha or beta thalassemia. The product will be marketed in the United States under the brand name Aqneusa, and the company emphasized that the approval covers both non-transfusion-dependent and transfusion-dependent patients, “regardless of transfusion burden.”
FDA approval and positioning
Chief Executive Officer Brian Goff called the approval a “historic day,” highlighting Aqneusa as the “first and only medicine” indicated for anemia in both alpha and beta thalassemia across transfusion needs. Goff also said Agios chose a separate brand name to “isolate the Aqneusa REMS to thalassemia,” adding that this provides regulatory clarity that the REMS does not apply to Pyrukynd in pyruvate kinase (PK) deficiency.
Unmet need and trial results supporting approval
Chief Medical Officer and Head of R&D Dr. Sarah Gheuens reviewed the disease burden in thalassemia, describing it as an inherited blood disorder that drives ineffective erythropoiesis and chronic hemolysis, leading to severe anemia and systemic complications. She cited risks including thrombosis, heart failure, liver injury, and cardiopulmonary disease, and said the burden contributes to reduced quality of life.
Gheuens said there had been no approved therapies for alpha thalassemia prior to Aqneusa and described limitations of existing options for beta thalassemia, including reliance on chronic transfusions and chelation (with iron overload and compliance challenges), in-office injections for luspatercept, and limited access to gene therapy due to intensive conditioning.
The FDA approval was supported by two global, placebo-controlled Phase 3 trials:
- ENERGIZE enrolled 194 non-transfusion-dependent alpha or beta thalassemia patients. The primary endpoint was a hemoglobin response defined as an increase of at least 1 g/dL in average hemoglobin from week 12 through week 24 versus baseline.
- ENERGIZE-T enrolled 258 transfusion-dependent alpha or beta thalassemia patients. The primary endpoint was a transfusion reduction response (TRR), defined as at least a 50% reduction in transfused red blood cell units with a reduction of at least two units over any consecutive 12-week period through week 48.
In ENERGIZE, Agios reported that Aqneusa met the primary and key secondary endpoints. The company said 42.3% of patients in the Aqneusa arm achieved the hemoglobin response, and among responders the average hemoglobin increase from baseline was 1.56 g/dL. Agios also reported a statistically significant improvement in FACIT-Fatigue scores: a change of 4.85 points in the Aqneusa arm versus 1.46 points for placebo. Gheuens said this was the first trial to show improvement in quality-of-life measures for non-transfusion-dependent patients. The company also cited improvements in hemolysis indicators such as indirect bilirubin and LDH.
In ENERGIZE-T, Agios reported that 30.4% of patients in the Aqneusa arm met the primary endpoint of transfusion reduction response. The company said Aqneusa demonstrated statistical significance across all three key secondary endpoints evaluating transfusion reduction and that 9.9% of patients achieved transfusion independence, defined as at least eight consecutive weeks without transfusion through week 48.
Gheuens also noted adverse reactions that occurred at a higher incidence than placebo included headache and insomnia.
Label details and REMS requirements
Agios said the final label supports broad use across adult thalassemia patients regardless of genotype or transfusion burden and describes Aqneusa’s mechanism as a pyruvate kinase activator as well as its oral administration.
The label includes a Risk Evaluation and Mitigation Strategy (REMS) tied to observations of adverse reactions suggestive of hepatocellular injury in five patients across ENERGIZE and ENERGIZE-T. According to Gheuens, the adverse reactions occurred within the first six months of exposure and liver tests improved upon discontinuation. She added that, to date, there have been no hepatocellular injury cases in other indications following the same pattern seen in the thalassemia pivotal trials.
The REMS program includes education and certification requirements for physicians, patients, and pharmacists, and requires liver testing at baseline and every four weeks for the first 24 weeks of treatment and as clinically indicated thereafter. Gheuens said the label includes a boxed warning for potential serious hepatocellular injury, advises against use in patients with cirrhosis, and recommends discontinuation if hepatic injury is suspected. In Q&A, she said a publication following a cohort over 38 years reported about 25% of patients developed cirrhosis in an untreated cohort, noting cirrhosis typically relates to iron overload in thalassemia.
Commercial launch timing, pricing, and early metrics
Chief Commercial Officer Tsveta Milanova outlined a U.S.-focused, “capital-efficient global commercial model,” saying the company is maintaining full economics and strategic focus in the U.S., which it described as the largest opportunity. Milanova said there are 6,000 diagnosed, actively managed adult thalassemia patients in the U.S., which Agios said it verified through claims data and account profiling. The company’s initial addressable population at launch is roughly 4,000 patients, including those receiving transfusions and chelation, older patients with comorbidities, and individuals with hemoglobin levels at or below 10 g/dL who experience anemia-related complications and fatigue.
Agios said it expects the REMS to be fully operational in late January and noted that prescriptions cannot be fulfilled until then. Milanova said that early adoption will be gated by health care provider REMS enrollment and completion of baseline liver testing required for patient certification. The company expects the initial time between prescription and treatment initiation to be roughly 10–12 weeks, driven by prior authorization timing and the REMS steps.
Milanova also said Agios plans to deploy about 40 dedicated sales representatives and that physician research found 86% of surveyed physicians indicated they plan to prescribe Aqneusa within six months of availability based on the clinical profile. She also said Agios found high REMS familiarity among clinicians, including that 94% of hematology oncologists reported prior REMS experience, and about two-thirds of HCPs anticipated no to minimal impact from REMS at launch.
On pricing, Milanova said Aqneusa will be introduced at approximately $425,000 per patient per year on a wholesale acquisition cost (WAC) basis. She said both Pyrukynd and Aqneusa are priced within the “rare disease price band,” and that distribution through a single specialty pharmacy under two different brand names will help ensure patients receive products on-label.
Chief Financial Officer Cecilia Jones said Agios plans to share Aqneusa prescription volume each quarter. For revenue reporting, she said the company plans to show mitapivat aggregate revenues and split between U.S. and ex-U.S. She also said the company expects some initial orders in the first quarter related to stocking and expects some prescriptions to be fulfilled in Q1 after the REMS becomes operational.
In discussing ex-U.S. dynamics, Milanova noted Agios has an approval in Saudi Arabia (KSA) that came in August and described a nomination-based prescribing process that requires hospital-level approvals and budget allocation before national procurement can expand access; she said that process can take about two years. For Europe, she said Agios expects a European Commission decision on the thalassemia label early 2026, followed by country-by-country pricing and reimbursement processes that can take 12 to 18 months, suggesting revenues may not arrive until later.
In closing remarks, Goff said the company will work to complete administrative elements of the REMS with the aim of making Aqneusa available in late January and reiterated plans to engage the FDA in the first quarter of next year to review Phase 3 RISE UP data in sickle cell disease and determine the regulatory path forward. He also said Agios will provide an update early next year on measures to reduce operating expenses and extend its cash runway while investing in the U.S. thalassemia launch.
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.
