Agios Announces Publication of Phase 3 ACTIVATE Study in New England Journal of Medicine Demonstrating Benefits of PYRUKYND® (mitapivat) for Adults with Pyruvate Kinase Deficiency
– In Adults with Pyruvate Kinase (PK) Deficiency Who Are Not Regularly Transfused, PYRUKYND® Significantly Increased Hemoglobin Level, Decreased Hemolysis and Improved Patient-Reported Outcomes –
– Following FDA Approval in February, PYRUKYND® Is the First and Only Disease-Modifying Treatment for Adults with PK Deficiency –
CAMBRIDGE, Mass., April 14, 2022 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, today announced that data from the core period of the pivotal Phase 3 ACTIVATE study of PYRUKYND® (mitapivat) in adults with pyruvate kinase (PK) deficiency who do not receive regular transfusions were published on April 14, 2022 in the New England Journal of Medicine. Data from this study were previously presented at the European Hematology Association (EHA) Virtual Congress held in June 2021. PYRUKYND® is a first-in-class, oral PK activator and the first and only approved disease-modifying treatment for this rare, debilitating, lifelong hemolytic anemia.
The publication can be accessed at the following link: https://www.nejm.org/doi/full/10.1056/NEJMoa2116634
“The results of the ACTIVATE study confirm that mitapivat, through its novel mechanism of activating pyruvate kinase and thus increasing ATP levels in red blood cells, successfully addressed the underlying cause of chronic hemolytic anemia in adults with PK deficiency with a wide array of genotypes,” said Hanny Al-Samkari, M.D., hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, an investigator in the pivotal ACTIVATE Phase 3 study and first author of this publication. “Improvements in the PK deficiency–specific patient-reported outcome measures further support the clinical efficacy of mitapivat and its benefits on health-related quality of life and reduction in symptom severity.”
“We have been pioneering the science of PK activation for more than a decade, and are pleased to have developed the first approved product for people with PK deficiency who previously had no disease-modifying treatment options,” said Sarah Gheuens, M.D., Ph.D., chief medical officer at Agios. “The results of the ACTIVATE study underscore the clinical value of PYRUKYND® and support our current efforts to deliver this medicine to as many patients as possible who may benefit from it.”
As reported in the publication, the ACTIVATE study met its primary endpoint, with 40 percent of patients randomized to PYRUKYND® achieving a hemoglobin response, defined as a =1.5 g/dL increase in hemoglobin concentration from baseline 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<0.001). Patients who received PYRUKYND® had a significantly greater response than those who received placebo with respect to each secondary endpoint, including average change from baseline in hemoglobin level; average change from baseline in markers of hemolysis including indirect bilirubin, lactate dehydrogenase (LDH) and haptoglobin levels; average change from baseline in markers of hematopoietic activity (reticulocyte percentage); and change from baseline in two PK deficiency–specific patient-reported outcome measures. The most common adverse events were nausea (in seven patients [18%] in the PYRUKYND® group and nine patients [23%] in the placebo group) and headache (in six patients [15%] and 13 patients [33%], respectively). Adverse events of grade 3 or higher occurred in 10 patients (25%) who received PYRUKYND® and five patients (13%) who received placebo.
PYRUKYND® was approved in February 2022 by the U.S. Food and Drug Administration (FDA) for the treatment of hemolytic anemia in adults with PK deficiency. PYRUKYND® is also under review by the European Medicines Agency (EMA) as a potential treatment for adults with PK deficiency, and Agios expects a regulatory decision in the EU by the end of 2022. Both the FDA and EMA have granted orphan drug designation to PYRUKYND® in PK deficiency. Learn more at www.PYRUKYND.com.
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 PYRUKYND® 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.
Agios conducted an additional pivotal Phase 3 study, ACTIVATE-T, in adults with PK deficiency who receive regular transfusions. The company is conducting an ongoing 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 PYRUKYND®.
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. For more information, please visit the websites of two U.S.-based independent patient advocacy groups dedicated to PK deficiency: PK Deficiency Foundation and Thrive with PK Deficiency.
About PYRUKYND® (mitapivat)
IMPORTANT SAFETY INFORMATION
Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (=10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.
Cautionary Note Regarding Forward-Looking Statements