Roche builds case for MS drug with two-year efficacy data

Roche has revealed new results from a phase 2 trial of its oral BTK inhibitor fenebrutinib in relapsing multiple sclerosis (MS) that suggest it can prevent progression of the disease for nearly two years.

The data come from an open-label extension (OLE) of the FENopta trial of fenebrutinib and raise expectations for the readouts of phase 3 studies in both relapsing and primary progressive MS that are due around the end of 2025.

48-week data from FENopta were reported last year at the 2024 ECTRIMS congress, showing that 99% of patients treated with fenebrutinib were free of new T1 gadolinium-enhancing lesions – markers of active inflammation – at that time point with an annualised relapse rate (ARR) of 0.04 and no change in disability measuring using the widely-used Expanded Disability Status Scale (EDSS).

Roche now has 96-week results from 93 of 99 patients in the study who enrolled in the OLE, with the ARR now reading at 0.06 and – once again – no disability progression apparent on the EDSS.

There were also zero new T1 gadolinium-enhancing lesions of that period, while new or enlarging T2 lesions, a marker for chronic disease burden, decreased from 6.72 at the end of the 12-week double-blind period in FENopta to 0.34 by 96 weeks.

"These data show that patients treated with fenebrutinib experienced an annualised relapse rate equal to one relapse every 17 years," said Roche's chief medical officer, Levi Garraway.

Fenebrutinib is the only reversible BTK inhibitor currently in phase 3 for MS, and Roche maintains that could translate into a cleaner side effect profile than other drugs in the class.

Now, attention is focused on data from three late-stage studies – FENhance 1 and 2 in relapsing MS and FENtrepid in primary progressive MS – that could set up filings in 2026.

Sanofi's rival drug tolebrutinib failed two phase 3 trials in relapsing MS, but hit the mark in a third study in non-relapsing secondary progressive MS and was accepted for a priority review in the latter indication by the FDA in March. It is also in a pivotal trial in primary progressive MSD – PERSEUS – with data due in the latter half of this year.

Merck KGaA's evobrutinib was the first BTK inhibitor to show proof-of-concept in a phase 2 MS trial, but it subsequently failed two phase 3 trials in relapsing MS last year and was shelved.

Meanwhile, Novartis has remibrutinib in phase 3 trials for relapsing-remitting MS, with a filing slated for 2027, while InnoCare's orelabrutinib – formerly partnered with Biogen before rights were handed back in 2023 – is in phase 2.

https://pharmaphorum.com/news/roche-builds-case-ms-drug-two-year-efficacy-data