Agios Announces Updated Data from Phase 1 Study of Mitapivat, First-in-Class PKR Activator, in Sickle Cell Disease
– Treatment with Mitapivat Induced Hemoglobin Increase of =1.0 g/dL in 6 of 11 (55%) Efficacy Evaluable Patients, Decreased Markers of Hemolysis, Reduced 2,3-DPG and Increased ATP –
– Safety Profile Generally Consistent with Previously Presented Data in Patients with Pyruvate Kinase Deficiency and Thalassemia –
– Data Support Advancement of Mitapivat to Pivotal Development in Sickle Cell Disease; Company Expects to Initiate Pivotal Program in 2021 –
– Company to Host Investor Event and Webcast Tomorrow, December 8, at 8:00 a.m. ET –
CAMBRIDGE, Mass., Dec. 07, 2020 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today reported updated data from a Phase 1 trial of mitapivat, the company’s first-in-class pyruvate kinase R (PKR) activator, in patients with sickle cell disease. The study is being conducted in collaboration with the National Institutes of Health (NIH) as part of a cooperative research and development agreement. Data from the study were featured in an oral presentation at the American Society of Hematology (ASH) Annual Meeting, which is being held virtually. Mitapivat is an investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated PKR enzymes.
As of the October 6, 2020 data cut-off, six of 11 efficacy evaluable patients (55%) achieved a hemoglobin increase of =1.0 g/dL from baseline. The mean maximal hemoglobin increase among all efficacy evaluable patients was 1.3 g/dL, and the mean maximal hemoglobin increase among responders was 1.9 g/dL. Treatment with mitapivat was associated with decreases in hemolytic markers such as bilirubin, lactate dehydrogenase (LDH) and reticulocytes. As expected, dose-dependent decreases in 2,3-diphosphoglycerate (2,3-DPG) and increases in adenosine triphosphate (ATP) levels were observed, consistent with the proposed mechanism of action. Adverse events (AEs) reported during the study were generally consistent with those previously reported in pyruvate kinase (PK) deficiency and thalassemia studies.
“The hemoglobin improvement, in conjunction with improvements in markers of hemolysis, induced by mitapivat in sickle cell disease patients is highly encouraging, particularly given the short duration patients are on treatment at the higher dose levels,” said Swee Lay Thein, M.B.B.S., F.R.C.P., F.R.C.Path., D.Sc., chief of the Sickle Cell Branch of the National Heart, Lung, and Blood Institute, NIH, and the principal investigator of the study. “I believe mitapivat may be a promising sickle cell disease treatment option with a well-tolerated safety profile and convenient oral administration. I look forward to further investigating the long-term effects of mitapivat in an ongoing sickle cell disease extension study and to working with Agios to continue to advance mitapivat on behalf of this patient community, a historically under-served population in tremendous need of new treatment options.”
“We are pleased to continue collaborating with Dr. Thein and her colleagues at the NIH to further elucidate mitapivat’s potential to improve red blood cell health, energy and longevity for people living with sickle cell disease, a debilitating, inherited, lifelong red blood cell disorder,” said Chris Bowden, M.D., chief medical officer at Agios. “We are excited by the updated results of this study and plan to build on our findings by initiating a pivotal study of mitapivat in adults with sickle cell disease next year.”
Updated Data from the Mitapivat Phase 1 Trial in Sickle Cell Disease
Efficacy and Pharmacodynamic Data
Mitapivat Clinical Development
In addition, Agios has two global, pivotal trials in adults with PK deficiency that are fully enrolled.
Agios is also conducting a Phase 2 study evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of treatment with mitapivat in adults with non-transfusion-dependent a- or ß-thalassemia. The trial is fully enrolled with 20 patients, and the primary endpoint is hemoglobin response, defined as a =1.0 g/dL increase in Hb concentration from baseline. Agios expects to report the final results from this Phase 2 trial at a medical meeting in 2021. The company also expects to initiate a Phase 3 pivotal program evaluating mitapivat in thalassemia, including both a-and ß-thalassemia, as well as transfusion dependent and non-transfusion dependent patient populations, in 2021.
Mitapivat has not received marketing authorization from any regulatory authority.
Investor Webcast Information
Cautionary Note Regarding Forward-Looking Statements