First results from the Phase 3 AGILE study, a multicenter, double-blind, randomized, placebo-controlled clinical trial in patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1-) mutation shows improved event-free survival (EFS) and various secondary outcomes.
The data also demonstrated complete remission (CR), defined as the proportion of participants who achieve a CR, overall survival (OS), defined as the time from date of randomization to the date of death due to any cause, and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS) with ivosidenib (AG-120; Tibsovo®; Servier Pharmaceuticals) in combination with azacitidine (Onureg®; Celgene Corporation, a Bristol-Myers Squibb Company) compared to azacitidine plus placebo.
The data will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) taking place December 11 – 14, 2021.
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year  The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis.  The five-year survival rate is approximately 27%. For 6% to 10% of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.
Acute lymphoblastic leukemia (ALL) is the most common form of childhood acute leukemia. It is a rapidly progressing cancer that starts in the bone marrow and spreads into the blood, where it can cause problems elsewhere in the body, such as in the spleen, thymus, lymph nodes, liver, testicles, and the central nervous system.
ALL represents approximately 12% of all leukemia cases worldwide and about 80% of childhood leukemia cases. The five-year survival rate for children with ALL is now about 90%.
Ivosidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test in newly-diagnosed AML the who are ≥ 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.
In addition, updated survival and response results from Phase 1 study of ivosidenib or enasidenib (AG-221; Idhifa®; Celgene Corporation, a Bristol‑Myers Squibb Company; licensed from Servier Pharmaceuticals) in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia with an IDH1 or IDH2 mutation.
“Our growing oncology portfolio is designed to tackle hard-to-treat cancers and deliver new therapies for patients in need,” said David K. Lee, Chief Executive Officer of Servier Pharmaceuticals.
“At this year’s ASH meeting, we are proud to present new data demonstrating significant clinical outcomes for patients living with AML.”
“We look forward to sharing our findings with the medical community around the world, leveraging our leadership in oncology to strengthen our commitment to patients with hematological malignancies,” said Claude Bertrand, Executive Vice President, R&D, Servier Group.
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE) – NCT03173248
Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation – NCT02632708
Highlights of Prescribing Information
Ivosidenib (AG-120; Tibsovo®; Servier Pharmaceuticals)(Prescribing Information)
Azacitidine (Onureg®; Celgene Corporation, a Bristol-Myers Squibb Company)(Prescribing Information)
Enasidenib (AG-221; Idhifa®; Celgene Corporation, a Bristol‑Myers Squibb Company; licensed from Servier Pharmaceuticals)(Prescribing Information)
 National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). Online. Last accessed on December 9, 2021.
 American Cancer Society. Acute Myeloid Leukemia (AML). Online. Last accessed on December 9, 2021.
 Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer. 2011 Feb;2(2):95-107. doi: 10.1177/1947601911408076. PMID: 21779483; PMCID: PMC3111245.
 DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, et al Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386-2398. doi: 10.1056/NEJMoa1716984. Epub 2018 Jun 2. PMID: 29860938.
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