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Agios Announces Initiation of Global Phase 3 Trial (ACTIVATE) of AG-348 in Adults with Pyruvate Kinase Deficiency Who Are Not Regularly Transfused

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Monday, June 18, 2018

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CAMBRIDGE, Mass. - Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases,  announced the initiation of the Phase 3 ACTIVATE trial evaluating AG-348, a first-in-class, selective, small molecule activator of the pyruvate kinase-R (PKR) enzyme. ACTIVATE is a randomized, placebo-controlled trial that will enroll approximately 80 adults with pyruvate kinase (PK) deficiency who do not receive regular blood transfusions. The trial is designed to demonstrate that treatment with AG-348 results in a sustained increase in hemoglobin in these patients.

"AG-348 is the first potential treatment for PK deficiency that targets the underlying cause of a patient's anemia and has demonstrated robust and sustained hemoglobin increases in adults with this disease who are not regularly transfused," said Chris Bowden, M.D., chief medical officer of Agios. "With the initiation of ACTIVATE, and the ongoing ACTIVATE-T study in patients who are regularly transfused, we are executing a comprehensive pivotal development plan for adults with this lifelong anemia who currently only have access to supportive care."

ACTIVATE Trial Design
The purpose of this Phase 3, 1:1 randomized, double-blind, placebo-controlled global trial is to evaluate the efficacy and safety of treatment with AG-348 in approximately 80 adults with PK deficiency across approximately 35 sites in 15 countries. Key eligibility criteria include a hemoglobin less than or equal to 10 g/dL and at least one non-missense mutation. Patients homozygous for the R479H mutation will not be eligible for the trial. The study design has two parts. Part 1 is a dose optimization period where patients start at 5 mg of AG-348 or placebo twice daily, with the flexibility to titrate up to 20 mg or 50 mg twice daily over a three month period to establish their individual optimal dose, as measured by maximum increase in hemoglobin levels. After the dose optimization period, patients will receive their optimal dose for an additional three months in Part 2. The primary endpoint of the study is the proportion of patients who achieve at least a 1.5 g/dL increase in hemoglobin sustained over multiple visits in Part 2 of the trial.

Ongoing ACTIVATE-T Trial and PEAK Registry
A pivotal trial of AG-348 in adults with pyruvate kinase deficiency who are regularly transfused (ACTIVATE-T) is ongoing. ACTIVATE-T is a global, single-arm trial of approximately 20 adults with PK deficiency designed to demonstrate that treatment with AG-348 reduces transfusion burden.
A global registry known as PEAK, for adult and pediatric patients with PK deficiency, is open for enrollment. PEAK is designed to develop a greater understanding of the long-term clinical implications of PK deficiency, including natural history of the disease, current treatments and associated outcomes, variability of clinical care and disease burden. The registry will enroll up to 500 patients across approximately 60 global sites and will follow patients for at least two years. Please refer to for additional information on the trials mentioned above.

About Pyruvate Kinase (PK) Deficiency and Genetic Background
PK deficiency is a rare inherited disease that presents as hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutations in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower pyruvate kinase enzyme activity and a decline in ATP (adenosine triphosphate) levels and a build-up of upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).

The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or interventions for other treatment- and disease-related morbidities. There is no approved therapy to treat the underlying cause of PK deficiency.

PK deficiency is an autosomal recessive disease whereby all patients inherit two mutations, one from each parent. More than 250 different mutations have been identified to date. The mutations observed in PK deficiency patients are classified in two main categories. A missense mutation causes a single amino acid change in the protein, generally resulting in some functional protein. A non-missense mutation is any mutation other than a missense mutation, generally resulting in little functional protein. It is estimated that 58 percent of patients with PK deficiency have two missense mutations, 27 percent have one missense and one non-missense mutation, and 15 percent have two non-missense mutations.

About Agios Pharmaceuticals, Inc.
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic diseases through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has an approved oncology precision medicine and multiple first-in-class investigational therapies in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company's website at

Renee Leck, 617-649-8299
Senior Manager, Investor Relations

Holly Manning, 617-844-6630
Associate Director, Corporate Communications

Source: Agios Pharmaceuticals, Inc.
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