Agios Outlines Key Clinical Development & Research Strategies
- Phase 3 Study of AG-221 in Relapsed/Refractory IDH2 Mutant Acute Myeloid Leukemia (IDHENTIFY) Initiated -
- Frontline Combination Development Strategy for AG-221 and AG-120 Announced -
- Company to Webcast Today's R&D Day -
"With our lead IDH programs progressing through Phase 1 expansion cohorts and the initiation of the Phase 3 AG-221 study with our collaboration partner
"At our core, Agios is a research-driven organization, and I'm proud that our scientists have discovered AG-519, a novel PK activator, which represents our fifth new investigational medicine in just seven years. We continue to conduct research that we believe will enable us to make important advances for patients," Dr. Schenkein continued.
IDH Program Updates
In clinical studies to date, AG-221 and AG-120, which target mutated IDH2 and IDH1, respectively, have demonstrated positive clinical single-agent activity with durable complete and partial responses and manageable safety profiles in patients with AML. Together with our collaboration partner
Agios today announced clinical development updates for AG-221 and AG-120 in AML, including:
Initiation of the AG-221 Phase 3 Study: The IDHENTIFY study of AG-221 is a Phase 3, international, multi-center, open-label, randomized clinical trial designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients 60 years or older with IDH2 mutant-positive AML that is refractory to or relapsed after second- or third-line therapy. Additional details can be found below and on www.clinicaltrials.gov. This study is being conducted by
Novel Design of the AG-221 and AG-120 Frontline Trials in AML:
- For Newly Diagnosed AML Patients Eligible for Intensive Chemotherapy: A Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy is planned for initiation by the end of 2015.
- For Newly Diagnosed AML Patients Not Eligible for Intensive Chemotherapy: A Phase 1/2 combination study of either AG-221 or AG-120 with VIDAZA® (azacitidine) is planned for initiation in the first quarter of 2016. This study has a Phase 1 component to determine the safety of the combinations, followed by a Phase 2 randomized component evaluating the safety and clinical activity of each investigational combination versus single-agent VIDAZA® using a primary endpoint of overall response rate.
ASH Data Presentations: New data from the ongoing Phase 1 dose-escalation and expansion studies of AG-221 and AG-120 in advanced hematologic malignancies have been accepted for presentation at the
American Society of Hematology(ASH) Annual Meeting and Exhibition taking place December 5-8, 2015in Orlando.
EORTC-NCI-AACR Data Presentation: The first data from the ongoing Phase 1 trial of AG-120 in advanced IDH1-mutant positive solid tumors have been accepted for oral presentation at
EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeuticstaking place November 5-9, 2015in Boston.
Pyruvate Kinase (PK) Deficiency Program Updates
Agios is pioneering the development of its small molecule enzyme activators in PK deficiency, a rare genetic metabolic disorder with no disease-altering therapies.
- AG-348: AG-348, a first-in-class orally available, potent, selective small molecule activator of pyruvate kinase-R (PKR), is on track and enrolling in DRIVE PK, a global Phase 2, open-label safety and efficacy trial in adult, transfusion-independent patients with PK deficiency.
- AG-519: Agios announced today the development of its second PKR activator, AG-519. This program provides clinical development optionality for our PK activator portfolio and potentially opportunities in other hemolytic anemias where PK activation may be therapeutic. The development plan for AG-519 includes a placebo-controlled Phase 1 study in healthy volunteers, which is planned for the first quarter of 2016. This study will be an integrated single ascending dose (SAD) and multiple ascending dose (MAD) trial.
Research Program Updates
Agios has advanced and led the emerging field of cancer metabolism with its novel IDH1 and IDH2 programs, demonstrating significant potential benefit for AML patients whose cancers carry these mutations. Agios' work in IDH exemplifies the company's strategy of targeting metabolic vulnerabilities. The company continues to discover novel metabolic targets that meet a high bar for future development. Today at its R&D day, Agios will describe:
- Its precision medicine strategy to discover novel cancer metabolism targets.
- Novel research approach to rare genetic diseases using allosteric modulation to correct the underlying dysfunction in metabolic pathways.
- The potential for PKR activators to provide clinical benefit in other indications, such as beta-thalassemia.
A live webcast of the company's R&D Day will begin today at
About the IDHENTIFY Phase 3 Study of AG-221
The Phase 3, international, multicenter, open-label, randomized clinical trial is designed to compare the efficacy and safety of AG-221 versus conventional care regiments in subjects 60 years or older with IDH2 mutant-positive AML refractory to or relapsed after second- or third-line therapy. Patients will be randomly assigned to receive either AG-221, 100 mg orally once a day for 28 days, or one of the conventional care regiments. The conventional treatment options include best supportive care only, azacitidine, low-dose cytarabine or intermediate-dose cytarabine. The primary endpoint of the trial is overall survival. The study is expected to enroll approximately 280 patients and is being conducted by
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 AG-348 and PK Deficiency
PKD is a rare inherited disease resulting from mutations in the PKR enzyme that result in hemolytic anemia, which is the accelerated destruction of red blood cells. The mutations in the PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by a decline in the energy metabolite ATP and a build-up of the metabolite 2,3-DPG. Agios scientists have previously reported that AG-348 is a potent activator of the wild-type and mutated PKR enzymes, resulting in restoration of ATP levels and a decrease in 2,3-DPG levels in patient blood ex vivo. 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. Currently, there is no approved therapy to treat the underlying cause of PKD. AG-348, a first-in-class orally available, potent, selective small molecule activator of PKR, was discovered by Agios scientists, and the company retains worldwide development and commercialization rights.
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic disorders of metabolism 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 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 Agios' product candidates targeting IDH1/IDH2 or pyruvate kinase-R mutations, including
Renee Leck, Senior Manager, Investor Relations and Public Relations Renee.Leck@agios.com 617-649-8299