US, EU regulators start swift reviews of Servier glioma drug


The US FDA and EMA in the EU have started accelerated reviews of Servier’s vorasidenib for IDH-mutated low-grade glioma, which is vying to become the first targeted therapy for this aggressive and incurable form of brain cancer.

The FDA has set an expected decision date of 20th August for its priority review of the marketing application, while EMA has started an accelerated assessment, with a verdict due sometime in the second half of the year.

Vorasidenib is an oral IDH1/2 inhibitor that can be dosed orally and is designed to cross the blood-brain barrier into the central nervous system.

It is the second of two IDH-targeting drugs that Servier acquired as part of its $1.8 billion takeover of Agios’ oncology business in 2021, which could rise to $2 billion if vorasidenib reaches the market for glioma.

The other drug, Tibsovo (ivosidenib), is already approved to treat IDH1-mutant acute myeloid leukaemia (AML). However, vorasidenib is seen as the biggest prize from the acquisition and a key part of Servier’s plans to grow its oncology sales to €3 billion ($3.2 billion) by 2030.

The FDA and EMA are reviewing data from the phase 3 INDIGO study, which tested vorasidenib as a monotherapy for patients with residual or recurrent IDH mutant low-grade glioma who have previously been treated with surgery.

In data presented at last year’s ASCO congress, vorasidenib was shown to reduce disease progression and death in grade 2 gliomas with IDH mutations compared to placebo and to delay the need for patients to undergo treatment with later-line and more toxic therapies.

Progression-free survival (PFS) more than doubled to 27.7 months compared to 11.1 in the control group, while the median time to the next treatment was 17.4 months for placebo, but had not been reached in the vorasidenib arm.

One red flag in the data was an increase in biomarkers for liver damage in some patients, including a couple of cases that reached life-threatening levels, although, Servier thinks that the risk can be managed effectively by clinicians.

Patients diagnosed with this type of glioma are typically young, otherwise healthy individuals and often only become aware of the cancer as a result of a seizure, and the risk of liver complications will be viewed in this context.

Treatment of the cancer has barely changed in decades, still relying on surgery – assuming the tumour is not in a critical area of the brain – as well as radiotherapy and chemotherapy.

IDH mutations are commonly seen in gliomas, accounting for somewhere between 50% and 81% of cases, according to figures from the US National Institutes of Health (NIH).

Servier has also filed vorasidenib in other markets, including Brazil, Canada, Australia, Israel, and Switzerland, and has said it intends to file in the UK if and when it gets a positive opinion on vorasidenib from the EMA’s human medicines committee, the CHMP.

21 February, 2024