Agios Announces Initiation of Phase 1b Frontline Trial of AG-221 or AG-120 in Combination with Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients
“The five-year survival rate for AML is just 20 to 25 percent, and treatment options for newly diagnosed AML patients have not changed in decades,” said
“Having established favorable safety profiles and durable single agent response rates for AG-221 and AG-120 in advanced AML, we believe there is a compelling case to evaluate our IDH mutant inhibitors in the frontline setting with standard of care,” said
About the Phase 1b Frontline Combination Trial of AG-221 or AG-120 in Newly Diagnosed AML Patients Eligible for Intensive Chemotherapy
The Phase 1b, multicenter, international, open-label clinical trial will evaluate the safety and clinical activity of AG-221 or AG-120 in combination with induction and consolidation therapy in patients with newly diagnosed AML with an IDH2 and/or IDH1 mutation who are eligible for intensive chemotherapy. The study will evaluate continuous dosing for up to one year with AG-221 administered at an initial oral dose of 100 mg once daily in patients with an IDH2 mutation or AG-120 administered at an initial oral dose of 500 mg once daily in patients with an IDH1 mutation. AG-221 or AG-120 will be administered with two types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and two types of AML consolidation therapies (mitoxantrone with etoposide [ME] or cytarabine).
The primary endpoint of the trial is to determine safety and tolerability, and the secondary endpoints include: characterization of pharmacokinetics, establishment of the recommended Phase 2 dose, and evaluation of 2-HG levels and clinical activity of the combination with standard induction. This study is open for enrollment and will include approximately twenty centers that will enroll up to 90 patients.
All patients will receive induction therapy in combination with AG-120 or AG-221. Patients who achieve a complete remission (CR), CR with incomplete platelet recovery (CRp) or CR with incomplete hematologic recovery (CRi) at the end of induction therapy will go on to receive consolidation therapy. Following consolidation therapy, patients may continue on maintenance therapy and receive daily treatment with AG-120 or AG-221 for up to one year, until relapse, development of an unacceptable toxicity or hematopoietic stem cell transplant (HSCT).
Please refer to www.clinicaltrials.gov for additional clinical trial details.
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the
About IDH Mutations and Cancer
IDH1 and IDH2 are two metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies, including AML. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH increases production of an oncometabolite 2-hydroxyglutarate (2HG) that alters the cells' epigenetic programming, thereby promoting cancer. 2HG has been found to be elevated in several tumor types. Agios believes that inhibition of the mutated IDH proteins may lead to clinical benefit for the subset of cancer patients whose tumors carry them.
About Agios/Celgene Collaboration
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic metabolic disorders through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has multiple first-in-class investigational medicines 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 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 Agios' product candidates targeting IDH mutations, including AG-221 and AG-120; its plans and timelines for the clinical development of AG-221 and AG-120; and the benefit of its strategic plans and focus. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "potential," "possible," "hope," "could," "would" 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, 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.
Renee Leck, Senior Manager, Investor Relations and Public Relations Renee.Leck@agios.com 617-649-8299