Suzhou, China, April 22, 2022 –The partner of CStone Pharmaceuticals (“CStone”, HKEX: 2616), Servier, today announced the publication of results from the Phase 3 AGILE trial of TIBSOVO® (ivosidenib tablets) in the New England Journal of Medicine (NEJM). The AGILE trial is a global Phase 3 double blinded placebo-controlled study in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) comparing TIBSOVO in combination with the chemotherapy azacitidine 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, and CStone is pursuing submission for this indication in China as well.
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 In China, there are about 75.3 thousand new cases of leukemia each year and approximately 59% are AML patients. 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 are thrilled that the publication of the compelling Phase 3 AGILE study data in a leading journal like NEJM, which reinforces the clinical importance of these results.” said, Dr. Jason Yang, Chief Medical Officer of CStone, “Patients with IDH1 mutant AML have a poor prognosis, especially for newly diagnosed patients who are not eligible for intensive chemotherapy. TIBSOVO in combination with azacitidine provide a new treatment option for this group of patients and we plan to communicate with the National Medical Products Administration (NMPA) of China with an aim to bring this innovative therapy to more Chinese patients as soon as possible.”
The data from the global Phase 3 AGILE study, showed 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 event-free survival (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 overall survival (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, 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 + CR 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). 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).
On July 19, 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. 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.
Currently, the National Medical Products Administration (NMPA) of China has approved the new drug application (NDA) of TIBSOVO (ivosidenib tablets) for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (R/R AML) who have a susceptible IDH1 mutation.
About 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 complete remission rate (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 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.
In China, TIBSOVO was selected in the list of the third batch of Overseas New Drugs Urgently Needed in Clinical Settings by the Center for Drug Evaluation, NMPA in China, and granted fast-track designation. As a potent and highly selective first-in-class oral IDH1 inhibitor, TIBSOVO was also recommended by the 2020 edition of the CSCO Guidelines for Diagnosis and Treatment of Hematological Malignancies due to its proven clinical advantages.
TIBSOVO® is currently approved in the U.S. as monotherapy for the treatment for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML), and for adults with newly-diagnosed AML with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in adult patients who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. In 2021, TIBSOVO® was the first and only targeted therapy approved for patients with previously treated locally advanced or metastatic cholangiocarcinoma with an IDH1-mutation as detected by an FDA-approved test.
The U.S. FDA has granted Breakthrough Therapy Designation for TIBSOVO in combination with azacitidine for this indication and Breakthrough Therapy Designation for TIBSOVO for the treatment of adult patients with relapsed or refractory myelodysplastic syndrome (MDS) with a susceptible IDH1 mutation.
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 January 2022.
2. American Cancer Society. Acute Myeloid Leukemia (AML). https://www.cancer.org/content/dam/CRC/PDF/Public/8674.00.pdf. Accessed January 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 January 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 January 2022.
7. Visser O. Incidence, survival and prevalence of myeloid malignancies in Europe. European Journal of Cancer. 2012; 3257-3266.
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