TIBSOVO is the first and only targeted therapy approved for patients with previously treated IDH1-mutated cholangiocarcinoma.
SUZHOU,China, August 27, 2021 – The partner of CStone Pharmaceuticals (“CStone”, HKEX: 2616), Servier Pharmaceuticals, a growing leader in oncology, announced that the U.S. Food and Drug Administration (FDA) approved TIBSOVO® (ivosidenib tablets) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation as detected by an FDA-approved test. TIBSOVO is the first and only targeted therapy approved for patients with previously treated IDH1-mutated cholangiocarcinoma.
The supplemental New Drug Application (sNDA) for TIBSOVO received Priority Review, which accelerated the review timeline and is typically given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists.
The FDA approval of this indication is supported by data from the ClarIDHy study, the first and only randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Results from the ClarIDHy study demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS) by an independent review committee (hazard ratio [HR] 0.37; 95% CI [0.25, 0.54], p<0.001).[1] The median PFS (95% CI) for TIBSOVO and placebo was 2.7 (1.6, 4.2) and 1.4 (1.4, 1.6) months, respectively. Thirty-two percent and 22% of patients randomized to TIBSOVO remained free of progression or death at 6 and 12 months, respectively, versus none on the placebo arm.
The study protocol specified that patients randomized to placebo could cross over to TIBSOVO at the time of disease progression, and a high proportion of patients in the placebo arm (70.5%) crossed over to TIBSOVO. The study also showed the key secondary endpoint of overall survival (OS) favoring patients randomized to TIBSOVO compared to those randomized to placebo; however, statistical significance was not reached.1 OS results are based on the final analysis of OS (based on 150 events which occurred 16 months after the final analysis of PFS. The median OS (95% CI) for TIBSOVO was 10.3 (7.8, 12.4) months; and placebo was 7.5 (4.8, 11.1) months without adjusting for crossover.
The safety profile observed in the study was consistent with previously published data.1 The most common adverse reactions (≥15%) in patients with cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.
Cholangiocarcinoma is a rare, aggressive cancer of the bile ducts within and outside of the liver. An estimated 8,000 people in the United States are diagnosed with cholangiocarcinoma each year. However, the actual number of these cases is likely to be higher, as cholangiocarcinoma can be hard to diagnose, and may be misclassified as other types of cancer.[2]
Servier has an exclusive collaboration and license agreement with CStone for the development and commercialization of TIBSOVO in Mainland China, Taiwan, Hong Kong, Macau and Singapore.CStone is conducting two registration trials for ivosidenib in Mainland China.
CS3010-101 is an ongoing phase I, multi-center, single-arm study in Chinese adults with R/R AML with a susceptible IDH1 mutation as the bridging study of the global pivotal AG120-C-001 study. The National Medical Products Administration of China has accepted the NDA of ivosidenib in adult patients with R/R AML who have a susceptible IDH1 mutation and this NDA has been granted priority review.
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 to placebo in combination with azacytidine, in adults with previously untreated IDH1-mutated AML. Servier announced the AGILE study met its primary endpoint of event-free survival (EFS). Treatment with TIBSOVO in combination with azacitidine compared to azacitidine in combination with placebo demonstrated a statistically significant improvement in EFS. Additionally, the trial met all of its key secondary endpoints, including complete remission rate (CR rate), overall survival (OS), CR and complete remission with partial hematologic recovery rate (CRh rate) and objective response rate (ORR). The safety profile of TIBSOVO in combination with azacitidine was consistent with previously published data.
CStone will work closely with NMPA to explore the registration pathway in China for ivosidenib in IDH1-mutated cholangiocarcinoma.
About Cholangiocarcinoma
Cholangiocarcinoma is a rare, aggressive cancer of the bile ducts within and outside of the liver. IDH1 mutations occur in up to 20% of cholangiocarcinoma cases in the US and are not associated with prognosis.[3] Prior to the approval of TIBSOVO, there were no approved targeted therapies for IDH1-mutated cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed advanced or metastatic disease.
About TIBSOVO
TIBSOVO is a prescription medicine used to treat:
About CStone
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 three drug approvals in Greater China, including two in Mainland China and one in Taiwan. 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.
Forward-looking statement
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Zhu A, et al. Final results from ClarIDHy, a global, phase 3, randomized, double-blind study of ivosidenib vs placebo in patients with previously treated cholangiocarcinoma and an isocitrate dehydrogenase 1 (IDH1) mutation. Presented at Gastrointenstinal Cancer Symposium 2021. Available at: https://www.servier.us/sites/default/files/2021-04/ASCO-GI21 ClarIDHy.pdf. ↑
American Cancer Society. Key Statistics for Bile Duct Cancer. Available at: https://www.cancer.org/cancer/bile-duct-cancer/about/key-statistics.html. ↑
Boscoe, A., Rolland, C., & Kelley, R. (2019). Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. Journal Of Gastrointestinal Oncology, 10(4), 751-765. Available at: https://jgo.amegroups.com/article/view/28868 ↑
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