Patients aged 12 years or older with astrocytoma or oligodendroglioma will be able to access oral vorasidenib on the NHS in England after the National Institute for Health and Care Excellence (NICE) recommended the treatment for routine use.

Under NICE’s final draft guidance, vorasidenib (Voranigo, Servier Laboratories) is indicated for patients with grade 2 astrocytoma or oligodendroglioma with susceptible isocitrate dehydrogenase (IDH1 or IDH2) mutations who have undergone surgery but do not yet need chemotherapy or radiotherapy.

The committee concluded that the once-daily oral therapy provides clinical benefit and represents a cost-effective use of NHS resources, taking into account the severity of the condition and its effect on quality and length of life. 

Karen Noble, PhD, director of research, policy and innovation at Brain Tumour Research described NICE’s decision as a significant step in expanding access to potentially life-changing therapies. She added, “Vorasidenib is the first new treatment to be approved for adult brain tumours in the UK for more than 20 years.”

Recently, vorasidenib was approved for use within NHS Scotland.

Disease Background and Drug Action

Gliomas are the most common type of brain tumour, arising from glial cells in the brain and spinal cord. Low-grade (grade 1-2) gliomas may remain stable initially but often progress, with up to 70% becoming high-grade within 10 years. Until now, there has been no disease-modifying treatment for patients whose tumour remains stable after surgery but who do not yet need radiotherapy or chemotherapy, leaving active surveillance as the standard approach. This can carry a substantial burden, with symptoms such as seizures, headaches, and cognitive changes, as well as a substantial psychological burden.

Vorasidenib is an oral, brain-penetrant small-molecule inhibitor of mutant IDH1 and IDH2 enzymes. It selectively inhibits these mutant enzymes, blocking the abnormal conversion of alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG). Lowering 2-HG levels may reduce dysregulation and the consequent block in cellular differentiation. This helps to promote tumour cell differentiation and inhibit proliferation in IDH-mutant glioma cells.

Clinical Evidence

The recommendation was based on evidence from the INDIGO trial, an ongoing multicentre, randomised, placebo-controlled study that enrolled 331 patients with IDH-mutant grade 2 oligodendroglioma or astrocytoma. At the March 2023 data analysis, 54 patients (32%) in the vorasidenib group and 104 patients (64%) in the placebo group had experienced disease progression. Median progression-free survival was not reached in the vorasidenib arm and was 11.4 months in the placebo arm. The trial also showed a 64% reduction in seizure rates among patients treated with vorasidenib. 

The NICE committee also noted several potential benefits that may not have been fully captured in the economic modelling, including psychological improvements for patients living with a disease that is expected to progress over time.

Patient Benefits and Special Populations

The committee highlighted key benefits of vorasidenib beyond slowing disease progression. It reduces seizures; helps patients maintain driving, work, and family life; and delays chemotherapy or radiotherapy, thereby postponing treatment-related toxicities and preserving day-to-day functioning. For patients aged 12-17, delaying potentially toxic treatment may also help protect brain development, support normal growth, and reduce disruption to schooling, with possible long-term societal impact.

Dosing and Implementation

Vorasidenib will be available as 40-mg and 10-mg tablets, with a 30-tablet pack priced at £15,000 and £7500 respectively, excluding VAT. The company has established a commercial arrangement that will provide the NHS with a confidential discount. 

Treatment should continue until disease progression occurs, following the stopping criteria outlined in the marketing authorisation. Under NHS regulations, integrated care boards, NHS England, and local authorities must comply with NICE recommendations within 90 days of publication.

Patients currently receiving vorasidenib outside this recommendation may continue their treatment under existing funding arrangements until they and their healthcare professional determine it appropriate to discontinue.