NEW YORK – The UK National Institute for Health and Care Excellence (NICE) on Tuesday recommended approval for Novartis' BRAF and MEK inhibitor combination, Finlee (dabrafenib) and Spexotras (trametinib), for the treatment of pediatric BRAF V600E mutation-positive glioma.
The recommendation is for low-grade glioma patients who need a systemic therapy or high-grade glioma patients who have received at least one prior radiation or chemotherapy treatment.
NICE recommended approval based on results from the Phase II TADPOLE trial. In that study, about half of patients (54.8 percent) with low-grade glioma responded to the Finlee-Spexotras combination compared to only 16.2 percent responding to the control arm of the chemotherapy combination, vincristine plus carboplatin. Median progression-free survival by independent review in the Finlee-Spexotras arm was 24.9 months versus 7.2 months in the control arm. Overall survival data was immature.
In the high-grade glioma arm of the TADPOLE study, the response rate was 56.1 percent and median progression-free survival by independent review was nine months on the Finlee-Spexotras combination. Overall survival results were also immature in this arm.
NICE noted in its final draft guidance that there was some uncertainty around the cost effectiveness of Finlee-Spexotras due to the lack of a comparator arm in the high-grade glioma cohort, the progression-free survival models used in the TADPOLE results, and how long patients would need to be treated with the combination. However, the committee concluded that the rarity of BRAF V600E-mutant glioma meant it was a low-risk decision to use in the National Health Service (NHS). The committee estimated about 30 children per year in the UK would be eligible for the combination treatment.
The list price for dabrafenib is £2,800 ($3,487) per 420-pack of 10 mg dispersible tablets and £376 ($468) per 4.7 mg bottle of 0.05 mg per ml powder for oral solution. NICE noted that Novartis is providing the drugs to the NHS at a confidential discount.
Last year, the US Food and Drug Administration approved the same combination, marketed as Tafinlar and Mekinist in the US, for pediatric patients with low-grade glioma harboring BRAF V600E mutations.
Finlee and Spexotras were also recommended by NICE last year as a first-line treatment for BRAF V600E-mutant advanced non-small cell lung cancer. The combination is also used in the UK for the treatment of BRAF V600-mutant melanoma.