Roche’s BTK drug fenebrutinib hits the mark in MS

Brain scan
Dmitriy Gutarev

Roche has made its case for BTK inhibitor fenebrutinib as a potential new oral therapy for multiple sclerosis, with a phase 2 readout that it says shows significant improvements in disease activity compared to placebo.

The FENopta biomarker study in patients with relapsing MS found that the drug significantly reduced the number of MS lesions in the brain detected using MRI scans with gadolinium imaging compared to placebo, and importantly did not identify any new safety concerns.

Two other oral BTK inhibitors in development for MS – Merck KGaA’s evobrutinib and Sanofi’s tolebrutinib – have been linked to liver toxicity that resulted in the FDA placing them on partial clinical hold. So far, that hasn’t been an issue with Roche’s drug or another BTK from Novartis called remibrutinib.

All four drugs are in phase 3 testing, in a closely-fought contest to bring a new oral therapy for MS to market that some neurologists have predicted could not only slow down progression of the disabling disease, but even potentially offer a functional cure.

In the new study, fenebrutinib hit its primary and secondary endpoints, showing an improvement using both the gadolinium T1 method – which looks for current disease activity marked by areas of active inflammation – and the T2 method which gives an overall picture of disease burden.

The T1 results showed that Roche’s drug reduced the total number of new lesions compared to placebo, while the T2 data revealed that it also cut the total number of new or enlarging lesions, with both results meeting the threshold for statistical significance.

Only the top-line findings are available for now, and Roche said detailed results will be reported at a future medical meeting. In the meantime, it is running three phase 3 trials across relapsing and progressive forms of MS, with a readout in primary progressive MS due later this year.

In the company’s first-quarter update, Roche’s chief executive Thomas Schinecker said fenebrutinib is going to be “one to watch”, because it is a reversible, non-covalent inhibitor of BTK that is highly selective and “doesn’t have the side effects that some of the other pharma companies have been reporting.”

In its favour, he said, was data from around 2,000 patients – including 1,000 with MS – who have been treated with the drug across multiple indications with no cases of confirmed liver toxicity.

Merck’s evobrutinib was the first BTK inhibitor to show proof-of-concept in relapsing MS in a phase 2 trial reported in 2019, reducing the cumulative number of brain lesions over time compared to placebo, with Sanofi reporting mid-stage results with tolebrutinib in 2021.

A recent GlobalData report suggested that tolebrutinib would be the leading BTK inhibitor for MS by 2030, with forecasted sales of approximately $2.6 billion across seven of the largest pharma markets.

Image by Dmitriy Gutarev from Pixabay