TIBSOVO is the first therapy targeting cancer metabolism approved in combination with azacitidine for patients with newly diagnosed IDH1-mutated acute myeloid leukemia
FDA approval based on data from the global, Phase 3 AGILE trial that demonstrated a statistically significant improvement in event-free survival and overall survival
Suzhou, China, 02 Jun, 2022 –The partner of CStone Pharmaceuticals (“CStone”, HKEX: 2616) Servier announced 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. 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.
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.7
Dr. Jason Yang, Chief Medical Officer of CStone, said, “Patients with IDH1-mutated AML have a poor prognosis, especially for newly diagnosed patients who are not eligible for intensive chemotherapy. TIBSOVO is the first therapy targeting cancer metabolism approved in combination with azacitidine for this group of patients and has improved median overall survival (OS) for about 3-fold (24 vs 7.9 months) as demonstrated in the registrational study AGILE. We are working closely with China National Medical Products Administration to deliver this innovative drug combination therapy to these AML patients in China.
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) and OS (HR = 0.44 [95% CI 0.27, 0.73]; 2-sided p = 0.0010). 5,6 TIBSOVO plus azacitidine treatment resulted in an approximately three-fold 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) Annual Meeting and Exposition,and published in the New England Journal of Medicine (NEJM) in April 2022.
In July 2019, CStone announced that the first patient in China was dosed in AGILE, the global registrational Phase 3 study of TIBSOVO. 16 centers in China participated in this global study.
In Jan 2022, the National Medical Products Administration (NMPA) of China has approved the new drug application (NDA) of TIBSOVO for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (R/R AML) who have a susceptible IDH1 mutation.
Servier is the owner of TIBSOVO’s rights and has granted an exclusive license to CStone to develop and commercialize the product in Mainland China, Taiwan, Hong Kong, Macau and Singapore.
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 In China, there are about 75.3 thousand new cases of leukemia each year and approximately 59% are AML patients. 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
About TIBSOVO (ivosidenib tablets)
TIBSOVO is an oral targeted IDH1 inhibitor. The NMPA of China has approved the NDA of TIBSOVO for the treatment of adult patients with relapsed/refractory acute myeloid leukemia who have a susceptible IDH1 mutation.
TIBSOVO is approved in the U.S.for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:
Newly Diagnosed Acute Myeloid Leukemia (AML)
- In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy
Relapsed or Refractory AML
- For the treatment of adult patients with relapsed or refractory AML
Locally Advanced or Metastatic Cholangiocarcinoma
- For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated
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).
CStone Pharmaceuticals (HKEX: 2616) is a biopharmaceutical company focused on researching, developing, and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received seven NDA approvals for four drugs. CStone's vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit: www.cstonepharma.com.
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1. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html. Accessed April 2022.
2. American Cancer Society. Acute Myeloid Leukemia (AML). https://www.cancer.org/cancer/acute-myeloid-leukemia/about.html. Accessed April 2022.
3. Kumar C. Genetic Abnormalities and Challenges in the Treatment of Acute Myeloid Leukemia. Genes Cancer. 2011; 2:95-107.
4. DiNardo C. Durable Remissions from Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. New England Journal of Medicine. 2018; 378:2386-98. Accessed April 2022.
5. Data on file. Servier. January 26, 2022.
6. ClinicalTrials.gov. Study of AG-120 (Ivosidenib) vs. Placebo in Combination with Azacitidine in Patients with Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE). Available at: https://clinicaltrials.gov/ct2/show/NCT03173248. Accessed April 2022.
7. FDA, Real-Time Oncology Review. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program, Accessed April 2022.
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