Agios Announces Updated Data from ACTIVATE and ACTIVATE-T Phase 3 Studies of Mitapivat in Pyruvate Kinase (PK) Deficiency at the European Hematology Association Virtual Congress
– Company Expects to File for Regulatory Approval for Mitapivat for the Treatment of Adults with PK Deficiency in the U.S. This Quarter and in the EU in Mid-2021 –
– Agios to Host Investor Webcast Today at 7:30 a.m. ET –
CAMBRIDGE, Mass., June 11, 2021 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat genetically defined diseases, today reported a full analysis of updated data, including patient-reported outcome (PRO) measures, from its global Phase 3 ACTIVATE and ACTIVATE-T studies of mitapivat in adults with pyruvate kinase (PK) deficiency. Data from the studies will be featured in oral presentations on Tuesday, June 15, at the European Hematology Association (EHA) Virtual Congress.
Consistent with previously announced topline data, the ACTIVATE and ACTIVATE-T studies met primary and secondary endpoints, including PRO outcomes that address symptom burden and quality-of-life impact of PK deficiency in adults. The safety profile observed in both studies was generally consistent with previously published data. Mitapivat is a first-in-class, investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase R (PKR) enzymes.
“Results from the ACTIVATE and ACTIVATE-T Phase 3 studies underscore the potential of mitapivat to be the first disease-modifying therapy for individuals with pyruvate kinase deficiency, a disease characterized by chronic hemolysis and associated long-term complications affecting multiple organ systems, regardless of the degree of anemia or transfusion status. New disease-modifying treatment approaches are needed, as current management strategies are supportive and include regular blood transfusions, which can lead to iron overload and splenectomy, which is also associated with short- and long-term risks,” said Andreas Glenthøj, M.D., Ph.D., associate professor, Department of Hematology, Rigshospitalet; Copenhagen, Denmark.
ACTIVATE Results Summary
ACTIVATE-T Results Summary
“For nearly a decade, Agios has been pioneering the science of PK activation. Results reported today from ACTIVATE and ACTIVATE-T continue to demonstrate the therapeutic impact of activating this pathway and provide the foundation for the first potential approval of a PK activator,” said Chris Bowden, M.D., chief medical officer at Agios. “In the weeks ahead, we look forward to working with regulatory authorities in both the U.S. and EU to rapidly bring mitapivat to pyruvate kinase deficiency patients as the first potentially disease-modifying therapy.”
Agios remains on track to submit a new drug application (NDA) in the U.S. in the second quarter of 2021 and a marketing authorization application (MAA) in the EU in mid-2021 for mitapivat in adults with PK deficiency.
ACTIVATE Trial Design
The study was designed with two parts. Part 1 was a dose escalation period in which patients started at 5 mg of mitapivt or placebo twice daily, with two potential dose escalations to 20 mg twice daily and 50 mg twice daily over a 12-week period. After the dose escalation period, patients received a fixed dose for an additional 12 weeks in Part 2.
The primary endpoint of the study was hemoglobin response, defined as a =1.5 g/dL increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at Weeks 16, 20 and 24 during Part 2 of the trial.
ACTIVATE-T Trial Design
The study was designed with two parts. Part 1 was a dose escalation period in which patients started at 5 mg twice daily of mitapivat, with two potential dose increases to 20 mg twice daily and 50 mg twice daily for up to 16 weeks. After the dose escalation period, patients received a fixed dose for an additional 24 weeks in Part 2.
The primary endpoint of the study was reduction in transfusion burden, defined as a reduction of =33 percent in the number of red blood cell units transfused during the 24-week fixed dose period compared with the historical transfusion burden standardized to 24 weeks. Participants who discontinued the study before completing at least 12 weeks of treatment in the fixed dose period were considered non-responders. The p-value is based on the binomial exact test of H0: transfusion reduction response rate =10% vs. H1: transfusion reduction response rate >10% at a 1-sided a=0.025.
Oral Presentation Information
Title: ACTIVATE: A Phase 3, randomized, multicenter, double-blind, placebo-controlled study of mitapivat in adults with pyruvate kinase deficiency who are not regularly transfused
Title: ACTIVATE-T: A Phase 3, open-label, multicenter study of mitapivat in adults with pyruvate kinase deficiency who are regularly transfused
Mitapivat Clinical Development
In addition, Agios completed 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 primary endpoint for the Phase 2 study was hemoglobin response, defined as a =1.0 g/dL increase in hemoglobin concentration from baseline at one or more assessments between Week 4 and Week 12. These results are also being reported as part of an oral presentation at the EHA Virtual Congress. Agios is conducting an extension study of mitapivat for adults previously enrolled in the Phase 2 study and is initiating two Phase 3 studies, ENERGIZE and ENERGIZE-T, in not regularly transfused and regularly transfused adults with thalassemia in the second half of 2021.
Mitapivat is also being evaluated as a potential treatment for sickle cell disease under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health. Mitapivat has been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and increase adenosine triphosphate (ATP), and through this mechanism, it may reduce hemoglobin S polymerization and red blood cell sickling. Preliminary clinical data establishing proof-of-concept for mitapivat in sickle cell disease were disclosed in June 2020, and updated data were presented at the American Society of Hematology (ASH) Annual Meeting in December 2020. Agios is initiating its pivotal Phase 2/3 study in sickle cell disease by year-end 2021.
Mitapivat has been granted orphan drug designation for the treatment of PK deficiency by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. Additionally, mitapivat has received orphan drug designation from the FDA for the treatment of thalassemia and sickle cell disease.
Mitapivat is not approved for use by any regulatory authority.
About PK Deficiency
PK deficiency is associated with serious complications, including gallstones, pulmonary hypertension, extramedullary hematopoiesis, osteoporosis and iron overload and its sequelae, which can occur regardless of the degree of anemia or transfusion burden. PK deficiency can also cause quality of life problems, including challenges with work and school activities, social life and emotional health. Current management strategies for PK deficiency, including red blood cell transfusions and splenectomy, are associated with both short- and long-term risks. There are no currently approved therapies for PK deficiency. For more information, please visit www.knowpkdeficiency.com.
Agios, in partnership with PerkinElmer Genomics, launched the Anemia ID program to offer no-cost genetic testing to eligible patients in the U.S. with suspected hereditary anemias, including PK deficiency. The program was created in response to feedback from patients, advocates and physicians about the need for improved diagnosis to inform disease management decisions. To learn more, please visit www.AnemiaID.com.
CONFERENCE CALL INFORMATION
Agios will host a virtual investor event today at 7:30 a.m. ET to review the mitapivat clinical data. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company's website at www.agios.com. The archived webcast will be available on the company's website beginning approximately two hours after the event.
Cautionary Note Regarding Forward-Looking Statements