Suzhou, China, November 14th, 2023 – The Partner of CStone Pharmaceuticals (“CStone”, HKEX: 2616) Servier, announced the U.S. Food and Drug Administration (FDA) has approved TIBSOVO® (ivosidenib tablets) for the treatment of patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). This is the fifth indication for TIBSOVO across IDH1-mutated cancers, and the first and only approved targeted therapy for people diagnosed with R/R MDS within this molecularly defined subset.
The FDA approval of this indication is supported by a pivotal Phase 1, open-label study in IDH1-mutated R/R MDS patients (n=18) where a complete remission (CR) rate of 38.9% and objective response rate (ORR) of 83.3% were documented in patients treated with TIBSOVO. In addition, the median time to CR was 1.9 months (range: 1.0, 5.6). At the time of data cutoff, the median duration of CR had not been reached (range: 1.9, 80.8+*) and the median overall survival was 35.7 months (range: 3.7*, 88.7*). Additionally, of the nine patients who were transfusion dependent with red blood cells or platelets at baseline, 66.7% (n=6) became independent of transfusions during any ≥56-day post-baseline period. Overall, treatment-related adverse events were consistent with the known safety profile of TIBSOVO.
An estimated 16,000 people in the U.S. are diagnosed with MDS each year.[1] Approximately 3.6% of MDS patients have an IDH1 mutation,[2] which is considered an early “driver” mutation.[3] For MDS patients with an IDH1 mutation, the prognosis has often been associated with worse overall outcomes and an increased risk of transformation to AML.2
TIBSOVO was granted Breakthrough Therapy designation by FDA for the treatment of adult patients with R/R myelodysplastic syndromes (MDS) with an IDH1 mutation and received Priority Review, which accelerated the review timeline and is granted to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions.[4]
TIBSOVO is a precision medicine that targets a specific type of mutation known as isocitrate dehydrogenase 1 (IDH1). TIBSOVO is approved for five indications globally, including U.S., European Union, Australia, United Arab Emirates (UAE), and China.
In the U.S., TIBSOVO is approved for the treatment of adults with IDH1-mutant relapsed or refractory AML and in monotherapy or in combination with azacitidine 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, as monotherapy for the treatment of adult patients with IDH1-mutant relapsed or refractory MDS, and for patients with previously treated IDH1-mutated cholangiocarcinoma.
In China, TIBSOVO is approved for the treatment of adult patients with relapsed or refractory AML who have a susceptible IDH1 mutation.
Servier has granted CStone a co-exclusive license for the development and an exclusive license agreement for the commercialization of TIBSOVO in Mainland China, Taiwan, Hong Kong, Macao and Singapore.
About the NCT02074839 Clinical Trial[5]
This Phase I, open-label multinational study evaluated the safety, tolerability, and clinical activity of ivosidenib in patients with relapsed or refractory myelodysplastic syndromes with an IDH1 mutation. The primary endpoint was complete remission (CR) plus partial remission (PR) rate and key secondary endpoints included duration of CR+PR, duration of transfusion independence, and time to transfusion independence.
About TIBSOVO® (ivosidenib tablets)
TIBSOVO is an oral targeted IDH1 inhibitor. The National Medical Products Administration (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)
Relapsed or Refractory AML
Relapsed or Refractory Myelodysplastic Syndromes (MDS)
Locally Advanced or Metastatic Cholangiocarcinoma
TIBSOVO is also approved by the European Commission as a targeted therapy in two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy; as well as in monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.
About Myelodysplastic Syndromes
Myelodysplastic Syndromes (MDS) are disorders in which progenitor (stem) cells do not mature into healthy blood cells.[6] In the U.S., approximately 16,000 new cases of MDS are reported each year.1 Approximately 3.6% of MDS patients have an IDH1 mutation,2 which is considered an early “driver” mutation.3 For MDS patients with an IDH1 mutation, the prognosis has often been associated with worse overall outcomes and in an increased risk of transformation to AML.2 Prior to the approval of TIBSOVO, there were no approved targeted therapies for this molecularly defined subset.
About CStone
CStone (HKEX: 2616) is a biopharmaceutical company focused on research, development, and commercialization of 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 management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 14 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received 12NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone’s vision is to bring innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit www.cstonepharma.com.
Forward-looking statements
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1.SEER MDS Incidence Rates. https://seer.cancer.gov/statistics-network/explorer/application.html?site=409&data_type=1&graph_type=2&compareBy=age_range&chk_age_range_1=1&chk_age_range_16=16&chk_age_range_62=62&
chk_age_range_122=122&chk_age_range_160=160&chk_age_range_166=166&hdn_rate_type=1&sex=1&race=1&hdn_stage=101&
advopt_precision=1&advopt_show_ci=on&hdn_view=1&advopt_show_apc=on&advopt_display=1;
U.S. Census Bureau Population Estimates 2017 National Population Projections Tables: Main Series (census.gov) https://www.census.gov/data/tables/2017/demo/popproj/2017-summary-tables.html. ↑
2.Thol, F., Weissinger, E. M., Krauter, J., Wagner, K., Damm, F., Wichmann, M., Göhring, G., Schumann, C., Bug, G., Ottmann, O., Hofmann, W. K., Schlegelberger, B., Ganser, A., & Heuser, M. (2010). IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica, 95(10), 1668–1674. https://doi.org/10.3324/haematol.2010.025494. Accessed May 19, 2023. ↑
3.DiNardo CD, et al. Leukemia. 2016;30(4):980-984. doi:10.1038/leu.2015.211. ↑
4.United States Food and Drug Administration (FDA). Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed June 27, 2023. ↑
5.Clinicaltrials.gov website. https://clinicaltrials.gov/ct2/show/NCT02074839. Accessed September 1, 2023. ↑
6.Pagliuca, S., Gurnari, C., & Visconte, V. (2021). Molecular Targeted Therapy in Myelodysplastic Syndromes: New Options for Tailored Treatments. Cancers, 13(4), 784. https://doi.org/10.3390/cancers13040784. ↑
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