Servier Pharmaceuticals recently announced the European Commission (EC) approval of Tibsovo (ivosidenib), as a targeted therapy in two difficult-to-treat oncology indications, acute myeloid leukemia (AML) and advanced cholangiocarcinoma. This marks the first IDH1 inhibitor approved in Europe and will be a game changer for patients with AML and cholangiocarcinoma in Europe, as Tibsovo addresses the need of IDH-1 mutated patients by providing a more targeted, and therefore potentially more efficacious treatment, says GlobalData, a leading data and analytics company.

GlobalData’s report ‘Acute Myeloid Leukemia: Epidemiology Forecast to 2029’ reveals that the introduction of Tibsovo may benefit an extra 7.1% of AML patients (around 200 patients every year) in the five major EU markets.

Draco Tai, Oncology and Hematology Analyst at GlobalData, comments: “AML is a highly heterogeneous disease driven by a wide range of cytogenetic mutations. The availability of targeted therapies for prevalent mutations, namely FLT3, IDH1/2 mutations, has been transformative for the treatment landscape in the US, resulting in increased overall survival (OS) and complete remission rates. Prior to the approval, patients harbouring FLT3 mutations were the only segment with a targeted treatment option available to them in Europe.”

Tibsovo is an oral IDH1 inhibitor first approved in the US in July 2018 for the treatment of AML patients in the first-line and relapsed/refractory (R/R) settings, as well as for R/R cholangiocarcinoma. In 2022, CStone Pharma gained NMPA approval for this agent to enter the Chinese market. However, the entry into the European market represents a five-year lag after its initial US launch. The delay was due to a voluntary withdrawal of the application for its use in the treatment of AML as a monotherapy in 2020, when the data from the Phase III Study AG120-C-001 was deemed insufficient by the authority for a market authorisation.

Tai continues: “Europe still lags behind the US in terms of the availability of targeted therapies for AML. Bristol Myers Squibb’s Idhifa (enasidenib) has been approved in the US since 2017 for treating patients with IDH2 mutations, while a second IDH1 inhibitor, Rigel Pharma’s Rezlidhia (olutasidenib), was approved in late 2022. Approximately 13% of European AML patients could benefit, should an IDH2 inhibitor be approved by the EC in the future. However, similar delays for European approval could be experienced by Idhifa and Rezlidhia as well, due to these clinical trials adopting complete remission rates as the primary efficacy endpoint, which may hinder European approval.”

EC approved the use of Tibsovo as a combination therapy with azacitidine for first-line IDH1 mutated AML patients who are ineligible for chemotherapy, and as a monotherapy for IDH1 mutated patients with advanced biliary tract cancer after first-line treatment.

Tai concludes: “Tibsovo may see faster uptake in Europe as a treatment for bile duct cancer, thanks to the recommendation in the European Society for Medical Oncology medical guidelines before Tibsovo’s approval, instilling confidence in physicians to prescribe the agent. The market of cholangiocarcinoma treatment is also set to be less competitive for Tibsovo. There are fewer drug candidates (18) in clinical development (from Phase I to Phase III) in Europe for this indication, compared to 33 drugs for AML, according to the GlobalData Pharma Intelligence Center.

“Emerging AML candidates including targeted therapies and immunotherapies, and against novel biomarkers are being developed. These are likely to pose a significant threat to Tibsovo’s market share in the coming years.”