On October 16, 2015 Agios Pharmaceuticals (NASDAQ:AGIO) reported its clinical development strategy for the company’s lead cancer metabolism and rare genetic metabolic disorders programs, along with insights into emerging research at its R&D Day today (Press release, Agios Pharmaceuticals, OCT 16, 2015, View Source [SID:1234507725]). Schedule your 30 min Free 1stOncology Demo! "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 Celgene, we are moving closer to our goal of providing people with advanced AML with transformational new medicines as quickly as possible," said David Schenkein, M.D., chief executive officer at Agios. "We will share our long-term vision for these programs at today’s R&D Day, as we hope to one day provide benefit to every patient diagnosed with an IDH mutant-positive cancer."
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"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 Celgene, Agios remains committed to bringing AG-221 and AG-120 to patients as quickly and efficiently as possible by leveraging a clinical development strategy that maximizes both speed and breadth.
Agios reported 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 Celgene.
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) (Free ASH Whitepaper) Annual Meeting and Exhibition taking place December 5-8, 2015 in 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 (Free EORTC-NCI-AACR Whitepaper) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place November 5-9, 2015 in 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.
Webcast
A live webcast of the company’s R&D Day will begin today at 9:00 a.m. ET and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for 30 days following the presentation.
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 Celgene. 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 American Cancer Society, the median age of onset is 66. Less than 10 percent of U.S. AML patients are eligible for bone marrow transplant and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 and IDH2 mutations are present in about 15 to 23 percent of AML cases.
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.