On June 9, 2023 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported updated data from the Phase 1 trial of TIBSOVO (ivosidenib tablets) as monotherapy for patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS) (Press release, Servier, JUN 9, 2023, View Source [SID1234632623]). The results presented today at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Annual Congress in Frankfurt, Germany demonstrate that the efficacy and safety profile of TIBSOVO may provide an important new treatment option for MDS patients within this molecularly defined subset.

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The Phase 1, open-label study included an evaluation of the safety, tolerability, and clinical activity of TIBSOVO in patients with IDH1-mutated R/R MDS. The primary endpoint was complete remission (CR) plus partial remission (PR) rate and key secondary endpoints included duration of CR plus PR, duration of transfusion independence, and time to transfusion independence.

In the efficacy analysis set (n=18), a complete remission (CR) rate of 38.9% and overall response rate (ORR) of 83.3% were documented in patients treated with TIBSOVO. In addition, the median time to CR was 1.87 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*).

"We are pleased to share these updated efficacy results that demonstrate durable remissions and an acceptable safety profile in patients with IDH1-mutated relapsed or refractory MDS at this year’s EHA (Free EHA Whitepaper) Congress," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "These data add to the growing body of evidence behind targeted IDH inhibition, and we look forward to taking the next steps with regulatory authorities to potentially expand the use of TIBSOVO in the United States to include the treatment of IDH1-mutated relapsed or refractory MDS."

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. Further, of the nine patients who were transfusion independent with red blood cells or platelets at baseline, 77.8% (n=7) maintained transfusion independence during any ≥56-day post-baseline period.

"Patients with IDH1-mutated relapsed or refractory MDS currently have no targeted therapy options, and outcomes are generally poor for those who experience disease progression after treatment with standard care," said Courtney D. DiNardo, M.D., MSCE, Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and investigator on the study. "This updated analysis demonstrates that TIBSOVO has the potential to improve outcomes in the treatment of IDH1-mutated relapsed or refractory MDS and reinforces the importance of molecular analysis to ensure we’re harnessing the potential benefit of targeted therapies."

Overall, treatment-related adverse events (TRAEs) were consistent with the known safety profile of TIBSOVO. Among 19 patients included in the safety analysis set, TRAEs occurred in eight (42.1%) patients, including a grade 1 QTc interval increase in one (5.3%) patient, grade 3 fatigue in one patient, and grade 3 hyponatremia in one patient, none of which led to discontinuation with treatment.

In 2019, the U.S. FDA granted Breakthrough Therapy designation for TIBSOVO (ivosidenib) for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test. Servier plans to submit a supplemental New Drug Application (sNDA) based on these results to the U.S. FDA for TIBSOVO in adult patients with R/R IDH1-mutated myelodysplastic syndromes.

TIBSOVO is currently approved in the U.S. as monotherapy 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. TIBSOVO was recently 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. TIBSOVO has also been approved in the U.S. and Australia for patients with previously treated IDH1-mutated cholangiocarcinoma. TIBSOVO is also approved in China[i] 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.

* Denotes a censored observation.

About the Study
In the Phase 1 dose-escalation and expansion study evaluating TIBSOVO in adults with advanced hematologic malignancies with IDH1 mutations, the clinical activity, safety, tolerability, pharmacokinetics and pharmacodynamics of TIBSOVO in adult patients with relapsed or refractory MDS with a susceptible IDH1 mutation is being assessed. (NCT03503409)

About Myelodysplastic Syndromes (MDS)
MDS comprises a diverse group of bone marrow disorders in which immature blood cells in the bone marrow do not mature or become healthy blood cells. The Leukemia and Lymphoma Society estimates that more than 20,000 people are diagnosed with MDS in the U.S. each year. Failure of the bone marrow to produce mature healthy cells is a gradual process, and reduced blood cell and/or reduced platelet counts may be accompanied by the loss of the body’s ability to fight infections and control bleeding. For roughly 30 percent of the patients diagnosed with MDS, this bone marrow failure will progress to AML1. Chemotherapy, supportive therapy, stem cell transplant, growth factors, and similar approaches are used to treat MDS.