Full Press Release Details
Agios Announces Publication of Data for Mitapivat from Core and Extension Phases of the DRIVE PK Study in
Patients with Pyruvate Kinase Deficiency in the New England Journal of Medicine
Increases >1.0 g/dL Observed in 50% of Patients in Core Period, Among Whom the Mean Maximum Hemoglobin Increase was 3.4 g/dL
Hemoglobin Responses Maintained in 19 Patients in the Extension Phase of the Study with Median Treatment Duration of 28.9 Months
Cumulative Safety Profile (Core Period plus Extension Phase) Continues to Support Long-term Twice Daily Dosing of
CAMBRIDGE, Mass., September 4, 2019 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the
field of cellular metabolism to treat cancer and rare genetic diseases, today announced that new data from the core and extension phases of the DRIVE PK Phase 2 study of mitapivat (AG-348) in adults with
pyruvate kinase (PK) deficiency were published in the September 5, 2019 issue of the New England Journal of Medicine. Mitapivat is an investigational,
first-in-class, oral, small molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes
that directly targets the underlying metabolic defect in PK deficiency, a rare, potentially debilitating, hemolytic anemia.
The DRIVE PK study is
the first clinical trial in adults with PK deficiency, which is a rare disease characterized by chronic hemolysis and long-term serious complications. Data from the study demonstrated rapid, clinically significant increases in hemoglobin in
50 percent of patients, and for patients in the extension phase, the response was sustained for up to 35 months, said Rachael Grace, M.D., of the Dana-Farber/Boston Children s Cancer and Blood Disorder Center and a principal
investigator for the study. There are no approved therapies for PK deficiency, and there are significant risks associated with current disease management strategies. By directly targeting the underlying metabolic defect in PK deficiency,
mitapivat has the potential to be the first disease-altering therapy for these patients.
Data from the extension phase of the DRIVE PK study
showed that patients who respond to long-term treatment with mitapivat had continued evidence of decreased hemolysis as demonstrated by directionally appropriate changes over time in hemoglobin, absolute reticulocyte counts, indirect bilirubin,
haptoglobin and lactate dehydrogenase, said Chris Bowden, M.D., chief medical officer at Agios. We are currently evaluating the safety and efficacy of mitapivat in adults with PK deficiency in our ongoing Phase 3 ACTIVATE and ACTIVATE-T studies, and we look forward to exploring mitapivat in the pediatric population.
ongoing global, open-label, Phase 2, safety and efficacy study evaluating mitapivat in adults with PK deficiency who do not receive regular transfusions. Patients were randomly assigned to receive either 50 mg or 300 mg of mitapivat twice daily for
a 24-week core period and eligible patients could continue treatment in an ongoing extension phase. As of the
August 31, 2018 data cutoff, 52 patients were randomized and 43 (83%) completed the core period. Thirty-six (69%) patients entered and 19 (37%) remain
in the extension phase with a median treatment duration of 28.9 months [range 21.6-34.8]. The median baseline hemoglobin was 8.9 g/dL (range, 6.5 12.3 g/dL). Nearly half (48%) of the patients reported a
history of treatment with iron chelation despite the absence of regular transfusions, while the majority of patients had a prior splenectomy (83%) and cholecystectomy (73%).
A safety analysis conducted for all 52
treated patients as of the data cut-off shows that adverse events associated with mitapivat were mainly low-grade and transient. The cumulative safety profile (core plus
extension phase) remained similar to that observed in the core period and continues to support long-term twice daily dosing.
In the efficacy analysis, 26 of 52 patients (50%) achieved a clinically significant maximum hemoglobin increase of >1.0 g/dL in the Core Period with
improvement in other markers of hemolysis as of the data cutoff.
Mitapivat Pivotal Development Plan
Agios has two ongoing global, pivotal trials in adults with PK deficiency that are on track to complete enrollment by
Learn more at activatetrials.com.
Mitapivat is not approved
for use by any regulatory authority.
About Pyruvate Kinase Deficiency and Genetic Background
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 levels and a build-up of
upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).
deficiency is associated with serious complications including gallstones, pulmonary hypertension, extramedullary hematopoiesis, cirrhosis, osteoporosis, and iron overload and its sequelae, which occur regardless of the degree of anemia or
transfusion burden. Current management strategies for PK deficiency, including blood transfusion and splenectomy, are associated with both short- and long-term risks.
More than 300 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 mutations1. For more information about PK deficiency, including the signs and symptoms, how to test for it, and how it
is currently managed, visit knowpkdeficiency.com.
The Peak Registry, a global, longitudinal study of children and adults with PK deficiency, has been
established to better understand the full spectrum of disease variability, including impact on quality of life. The Registry is open and recruiting patients. Learn more at www.peakregistry.com.
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 and adjacent areas of biology. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has two approved oncology precision medicines 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 www.agios.com.
Cautionary Note Regarding Forward-Looking
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 for the further clinical development of mitapivat and Agios strategic plans and prospects. The words anticipate,
believe, estimate, expect, intend, may, plan, predict, project, would, could, potential, possible,
hope and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and
uncertainties that may cause actual events or results to differ materially from Agios current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or
complete necessary preclinical and clinical development phases; that positive safety and efficacy findings observed in early stage clinical trials will be replicated in later stage trials; or that development of any of Agios product candidates
will successfully continue. There can be no guarantee that any positive developments in Agios business will result in stock price appreciation. Management s expectations and, therefore, any forward-looking statements in this press release
could also be affected by risks and uncertainties relating to a number of other important factors, including: Agios results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from
ongoing and future studies; the content and timing of decisions made by the U.S. FDA and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios ability to obtain and maintain
requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios ability to obtain, maintain and enforce patent and other intellectual property
protection for any product candidates it is developing; Agios ability to maintain key collaborations; and general economic and market conditions. These and other risks are described in greater detail under the caption Risk Factors
included in Agios public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information, future events or otherwise.
1 Bianchi P et al. poster, 2017 ASH Annual Meeting
Holly Manning, 617-844-6630
Associate Director, Investor Relations