Agios Announces Phase 3 ACTIVATE-T Trial of Mitapivat Achieved Primary Endpoint in Adults with Pyruvate Kinase Deficiency Who Are Regularly Transfused
– 37 Percent of Patients Treated with Mitapivat Achieved ≥33% Reduction in Transfusion Burden Compared to Individual Historical Transfusion Burden Standardized to 24 Weeks (1-Sided p=0.0002) –
– 22 Percent of Patients Treated with Mitapivat Were Transfusion-Free During the 24-Week Fixed Dose Period –
– Safety Profile Consistent with Previously Reported Data –
– Company Expects to File for Regulatory Approval for Mitapivat for the Treatment of Adults with Pyruvate Kinase (PK) Deficiency in the
Agios recently reported that its global, randomized, double-blind, placebo-controlled Phase 3 ACTIVATE trial of mitapivat in adults with PK deficiency who do not receive regular transfusions met its primary endpoint, with 40 percent of patients randomized to mitapivat achieving a hemoglobin response, defined as a ≥1.5 g/dL sustained increase in hemoglobin concentration from baseline, compared to 0 patients randomized to placebo (2-sided p<0.0001). Agios anticipates filing for regulatory approval based on data from ACTIVATE and ACTIVATE-T in the
“Based on results from both the ACTIVATE and ACTIVATE-T Phase 3 trials, we believe mitapivat has the potential to make a meaningful difference for people living with pyruvate kinase deficiency, a debilitating, lifelong hemolytic anemia characterized by serious complications regardless of patients’ transfusion status. The ACTIVATE-T study represents our first study of mitapivat in regularly transfused patients, and when taken together with the ACTIVATE results, demonstrates mitapivat’s potential clinical benefit for patients regardless of transfusion burden,” said
Results from the ACTIVATE-T trial were as follows:
- 37 percent of patients dosed with mitapivat (n = 10 of 27) achieved a ≥33% reduction in transfusion burden in the 24-week fixed dose period compared with individual historical transfusion burden standardized to 24 weeks (1-sided p=0.0002).
- 22 percent of patients dosed with mitapivat (n = 6 of 27) were transfusion-free during the 24-week fixed dose period.
- Treatment with mitapivat showed a reduction in the annualized total number of red blood cell units transfused during the study compared with the historical transfusion burden.
- The safety profile observed in the study was consistent with previously reported data.
Agios is conducting a full analysis of the ACTIVATE-T results and expects to submit the complete results of the trial for presentation at the
ACTIVATE-T Trial Design
ACTIVATE-T is a global, multicenter, open-label study to evaluate the efficacy and safety of mitapivat in adult patients with PK deficiency who are regularly transfused, defined as receiving six or more transfusions in the past 52 weeks. The trial enrolled 27 patients across
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 α=0.025.
ACTIVATE-T is one of two studies intended to support a marketing application for mitapivat in patients with PK deficiency. In addition to the ACTIVATE-T trial, Agios recently reported topline results from the global Phase 3 ACTIVATE trial of mitapivat in adults with PK deficiency who do not receive regular transfusions. A full analysis of the data – including patient-reported outcomes (PRO) – is expected to be submitted for presentation at the
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. Results from the study are expected to be submitted for presentation at the
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, in partnership with PerkinElmer Genomics, launched the Anemia ID program to offer no-cost genetic testing to eligible patients in the
Agios is focused on discovering and developing novel investigational medicines to treat malignant hematology, solid tumors and genetically defined 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 based on data from ACTIVATE and ACTIVATE-T in the
Director, Investor Relations
Associate Director, Corporate Communications
Source: Agios Pharmaceuticals, Inc.