Agios Announces the Phase 3 ACTIVATE Trial of Mitapivat Achieved Its Primary Endpoint in Adults with Pyruvate Kinase Deficiency Who Are Not Regularly Transfused
– 40 Percent of Patients Treated with Mitapivat Achieved a Sustained Hemoglobin Increase of ≥1.5 g/dL Compared to 0 Placebo Patients (p<0.0001) –
– Safety Profile Consistent with Previously Reported Data –
– Topline Data from the Mitapivat Phase 3 ACTIVATE-T Trial in Regularly Transfused PK Deficiency Expected in Q1 2021 –
“The robust, clinically meaningful efficacy and safety results from the ACTIVATE study underscore mitapivat’s potential to be the first disease-modifying therapy for people with pyruvate kinase deficiency, a chronic, lifelong hemolytic anemia that often leads to serious physical and quality of life complications. With only supportive therapy currently available, there is tremendous unmet need in this community, and we are proud to advance a promising therapeutic candidate for these patients,” said
Results from the ACTIVATE trial were as follows:
- 40 percent of patients randomized to mitapivat achieved a 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 the fixed-dose period, compared to 0 patients randomized to placebo (2-sided p<0.0001)
- Treatment with mitapivat demonstrated statistically significant improvements over placebo across pre-specified key secondary endpoints, including average change from baseline in hemoglobin concentration at Weeks 16, 20, and 24 during the fixed-dose period; markers of hemolysis (indirect bilirubin, haptoglobin, serum lactate dehydrogenase [LDH] activity); and markers of hematopoietic activity (reticulocyte percentages).
- The safety profile observed in the study was generally consistent with previously reported data.
- There were no AEs leading to discontinuation in either the mitapivat or the placebo arm.
Agios is conducting a full analysis of the ACTIVATE data, including patient-reported outcomes (PRO) which are not yet available. The company expects to submit the complete results of the trial for presentation at the
Agios anticipates filing for
ACTIVATE Trial Design
ACTIVATE is a Phase 3, global, double-blind, placebo-controlled trial with a 1:1 randomization evaluating the efficacy and safety of mitapivat as a potential treatment for adults with PK deficiency who do not receive regular transfusions. Patients were required to have a hemoglobin concentration less than or equal to 10.0g/dL. The trial randomized 80 patients.
The study was designed with two parts. Part 1 was a dose escalation period in which patients started at 5 mg of mitapivat 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 is one of two studies intended to support a marketing application for mitapivat in patients with PK deficiency. In addition to the ACTIVATE trial, Agios has fully enrolled the global, pivotal Phase 3 ACTIVATE-T trial in adults with PK deficiency who receive regular transfusions. The primary endpoint of this single-arm trial is the proportion of patients who achieve a reduction in transfusion burden compared to individual historical transfusion burden standardized to 24 weeks. Agios anticipates reporting topline ACTIVATE-T data in Q1 2021. Agios is also enrolling an extension study for adults with PK deficiency previously enrolled in ACTIVATE or ACTIVATE-T, which is designed to evaluate the long-term safety, tolerability and efficacy of treatment with mitapivat.
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 α- or β-thalassemia. The trial is fully enrolled, and the primary endpoint is hemoglobin response, defined as a ≥1.0 g/dL increase in Hb concentration from baseline at one or more assessments between Week 4 and Week 12. Agios expects to initiate a Phase 3 pivotal program evaluating mitapivat in thalassemia, including both α- and β-thalassemia, as well as transfusion dependent and non-transfusion dependent patient populations, in 2021.
In addition, mitapivat is being evaluated as a potential treatment for sickle cell disease under a Cooperative Research and Development Agreement (CRADA) with the U.S.
Mitapivat has been granted orphan drug designation for the treatment of PK deficiency by the
Mitapivat is not approved for use by any regulatory authority.
About PK Deficiency
Pyruvate kinase (PK) deficiency is a rare, inherited disease that presents as chronic hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutations in PKR genes cause a deficit in cellular energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate (ATP) levels and a build-up of upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).
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 is focused on discovering and developing novel investigational medicines to treat malignant hematology, solid tumors and rare genetic diseases through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across these three therapeutic areas, Agios has two approved oncology precision medicines and multiple first-in-class investigational therapies in clinical and/or preclinical development. For more information, please visit the company's website at www.agios.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding: the potential benefits of mitapivat; Agios’ plans to file for regulatory approval in PK deficiency in both the
Director, Investor Relations
Associate Director, Corporate Communications
Source: Agios Pharmaceuticals, Inc.