Ivosidenib Approved for Acute Myeloid Leukemia & Advanced Cholangiocarcinoma

Listen to this News

Recently the European Commission (EC) announced the approval of 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. This drug is being marketed by Servier Pharmaceuticals as Tibsovo and provides a more targeted, and therefore potentially more efficacious treatment.

‘European Commission approved the use of Ivosidenib, an IDH1 gene inhibitor for targeted therapy in acute myeloid leukemia (AML).’

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 ().

This has resulted in increased overall survival (OS) and complete remission rates. Before the approval, patients harboring FLT3 mutations were the only segment with a targeted treatment option available to them in Europe.

Ivosidenib with Chemotherapy New Option for Acute Myeloid Leukemia in Europe

Tibsovo was 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 market authorization.

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.

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 for 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.

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.

References:

1. FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation - (https:aacrjournals.org/clincancerres/article/25/11/3205/81450/FDA-Approval-Summary-Ivosidenib-for-Relapsed-or )
2. Advances in targeted therapy for acute myeloid leukemia - (https:biomarkerres.biomedcentral.com/articles/10.1186/s40364-020-00196-2 )

Source: Medindia