On April 21, 2022 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported the publication of results from the Phase 3 trial of TIBSOVO (ivosidenib tablets) in the New England Journal of Medicine (NEJM) (Press release, Servier, APR 21, 2022, View Source [SID1234612886]). The AGILE trial is a global Phase 3 double blinded placebo-controlled study of TIBSOVO in combination with the chemotherapy azacitidine in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) compared to azacitidine in combination with placebo. The study met the primary and all key secondary endpoints including overall survival. Servier is actively working with the FDA and health authorities across the globe to potentially bring this new indication to market.
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"Patients with IDH1-mutated AML have a poor prognosis and have few, if any, treatment options, especially for newly diagnosed patients who are not eligible for intensive chemotherapy," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier Pharmaceuticals. "The publication of the compelling Phase 3 AGILE study data in NEJM, reinforces the clinical importance of these results and supports Servier’s ongoing pursuit to serve patients with IDH1-mutated malignancies."
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 estimated in the U.S. each year.1,2 The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis.3 The five-year survival rate is approximately 29.5%.1 IDH mutations are present in about 6 to 10 percent of AML cases.4
"We have significantly strengthened our position in oncology following the successful acquisition of the Agios Pharmaceuticals’ oncology business in 2021," said Claude Bertrand, Executive Vice President, Research and Development, Servier. "Servier has placed oncology among its priorities and allocates more than 50% of its R&D budget to fighting cancer. This strategy initiated by the Group is now bringing results with new treatments and future indications for patients with hard-to-treat cancers."
The data from the global Phase 3 AGILE study show that TIBSOVO is the first IDH1 mutation specific targeted therapy to demonstrate improved event-free survival (EFS) and overall survival (OS) in combination with azacitidine compared to azacitidine plus placebo. Treatment with TIBSOVO in combination with azacitidine demonstrated a statistically significant improvement in EFS (hazard ratio [HR] = 0.33, 95% confidence interval [CI] 0.16, 0.69, 1-sided P = 0.0011).5,6 The combination of TIBSOVO with azacitidine showed a statistically significant improvement in OS (HR = 0.44 [95% CI 0.27, 0.73; 1-sided P = 0.0005), with a median OS of 24.0 months vs. 7.9 months in the placebo + azacitidine arm.
In addition, the complete remission (CR) rate was 47.2% (n = 34/72) for TIBSOVO in combination with azacitidine vs. 14.9% (n = 11/74) for placebo plus azacitidine (P < 0.0001). CR + complete remission with partial hematologic recovery rate (CR + CRh rate) was 52.8% (n = 38/72) for TIBSOVO in combination with azacitidine vs. 17.6% (n = 13/74) for placebo plus azacitidine (P < 0.0001).The objective response rate (ORR) was 62.5% (n = 45/72) for TIBSOVO in combination with azacitidine vs. 18.9% (n = 14/74) for placebo plus azacitidine (P < 0.0001).
TIBSOVO[*] is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML, and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Recently, TIBSOVO was approved as a first and only targeted therapy for patients with previously treated IDH1-mutated cholangiocarcinoma.
About the NCT03173248 AGILE Phase 3 AML Trial
The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy). The study’s primary endpoint is EFS, defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.
Key secondary endpoints included CR rate, 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; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; 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).
About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) a cancer of blood and bone marrow characterized by rapid disease progression, 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.1,2,7 AML incidence significantly increases with age, and the median age of diagnosis is 68.1 The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML.3 The five-year survival rate is approximately 29.5%.1 For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.4