On May 25, 2022 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that the U.S. Food and Drug Administration (FDA) approved TIBSOVO (ivosidenib tablets) in combination with azacitidine for the treatment of patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy (Press release, Servier, MAY 25, 2022, View Source [SID1234615052]). TIBSOVO is the first therapy targeting cancer metabolism approved in combination with azacitidine for patients with newly diagnosed IDH1-mutated AML. The AGILE trial was the only Phase 3 trial designed specifically for newly diagnosed patients with IDH1-mutated AML who are ineligible for intensive chemotherapy.

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The supplemental New Drug Application (sNDA) for TIBSOVO received Priority Review and was reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.1

"Today’s approval builds on the established body of evidence for TIBSOVO, which is now approved across multiple IDH1-mutated cancer types," said David K. Lee, Chief Executive Officer, Servier Pharmaceuticals. "As a leader in oncology pioneering the science behind targeted IDH inhibition, we are proud to bring a new therapeutic option to the acute myeloid leukemia community and remain committed to pushing the boundaries of healthcare innovation in oncology and beyond."

The expanded approval of TIBSOVO is supported by data from the AGILE study, a global, Phase 3 trial in patients with previously untreated IDH1-mutated AML. Results from the AGILE trial demonstrated a statistically significant improvement in event-free survival (EFS) (hazard ratio [HR] = 0.35 [95% CI 0.17, 0.72], 2-sided p-value = 0.0038)2 and overall survival (OS) (HR = 0.44 [95% CI 0.27, 0.73]; 2-sided p = 0.0010). TIBSOVO plus azacitidine treatment resulted in a threefold improvement in median OS (24 months) compared to placebo plus azacitidine (7.9 months) as a first-line treatment for IDH1-mutated AML. Results from the AGILE study were presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, and recently published in the New England Journal of Medicine (NEJM).

"Acute myeloid leukemia is a rapidly progressing, difficult-to-treat blood cancer with a poor prognosis," said Eytan M. Stein, M.D., Director, Program for Drug Development in Leukemia, Leukemia Service, Department of Medicine at Memorial Sloan Kettering Cancer Center. "In addition to a favorable safety profile, TIBSOVO is the first therapy targeting cancer metabolism to demonstrate an impressive, significant benefit in event-free survival and overall survival in combination with azacitidine, underscoring its importance as part of a new combination regimen for patients with newly diagnosed IDH1-mutated acute myeloid leukemia who are not candidates for intensive induction chemotherapy."

AML is a difficult-to-treat cancer of the blood and bone marrow and is one of the most common types of leukemia in adults with approximately 20,000 new cases estimated in the U.S. each year.3,4 IDH1 mutations are present in about 6 to 10 percent of AML cases.5

"People living with acute myeloid leukemia, especially those who are newly diagnosed and are not eligible for intensive chemotherapy, have had few treatment options," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "Today’s approval of TIBSOVO in combination with azacitidine represents a major advancement for patients with newly diagnosed IDH1-mutated acute myeloid leukemia in the United States, and we look forward to continuing our engagement with regulatory authorities worldwide."

The combination of TIBSOVO plus azacitidine demonstrated a safety profile consistent with previously published data. The most common adverse reactions (≥10%) in newly diagnosed AML patients receiving TIBSOVO in combination with azacitidine were nausea, vomiting, electrocardiogram QT prolonged, insomnia, differentiation syndrome, leukocytosis, hematoma, hypertension, arthralgia, dyspnea, and headache. The select laboratory abnormalities (≥10%) were leukocytes decreased, platelets decreased, hemoglobin decreased, neutrophils decreased, lymphocytes increased, glucose increased, phosphate decreased, aspartate aminotransferase increased, magnesium decreased, alkaline phosphatase increased, and potassium increased.

The recommended dosage of TIBSOVO for newly diagnosed IDH1-mutated AML is 500mg once daily via oral administration.

In an effort to support the patient communities it serves, Servier Pharmaceuticals recently introduced ServierONE Patient Support Services, a program that offers one-on-one support to help patients who are prescribed TIBSOVO or other Servier products navigate their cancer journey. Eligible patients will have access to financial assistance, emotional support and other resources. More information can be found at www.servierone.com.

TIBSOVOi is also 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-mutated AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Last year, TIBSOVO garnered its first approval in a non-hematologic malignancy for patients with previously treated IDH1-mutated cholangiocarcinoma.

About the NCT03173248 AGILE Phase 3 AML Trial 6
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 event-free survival (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.2,3 AML incidence significantly increases with age, and the median age of diagnosis is 68.2 The five-year survival rate is approximately 29.5%.2 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.5