Roche’s fenebrutinib cuts relapses in MS amid safety concerns

Roche is hoping to bring the the first and only high-efficacy oral for both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) to market. Now, Phase III study results seem to support this hope: Roche said its investigational non-covalent Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib significantly reduced relapses in RMS, with Phase III FENhance 1 and 2 showing annualised relapse rate reductions of 51.1% and 58.5% versus teriflunomide, respectively. The company said the effect equates to roughly one relapse every 17 years, and that the totality of data for RMS and PPMS will be submitted to regulators.

In addition to the relapse data, the studies showed marked reductions in MRI activity, including new T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, while disability progression trends also moved in the right direction, even if those results did not yet clearly separate on all measures. “The fenebrutinib data across three pivotal studies strongly support its potential to benefit people with both RMS and PPMS,” said Levi Garraway, Roche’s Chief Medical Officer. After Sanofi’s tolebrutinib underperforming, Roche hopes the data will give it an edge in the race for a high-efficacy MS treatment.

Death imbalance raises concerns

But the headline efficacy comes with a caveat. Roche reported an imbalance in fatalities across the two RMS studies, with one death in the teriflunomide arm and seven in the fenebrutinib arm during the reporting period, plus one additional death afterwards. The company stressed the causes varied from infections and diabetes complications to bleeding, suicide, an accident and one death of unknown cause.

Roche noted that liver enzyme elevations above three times the upper limit of normal were comparable between arms, and infections and serious adverse events were also broadly in line, which suggests the safety picture is not straightforward. That leaves fenebrutinib in an interesting place: the efficacy looks very strong, but the death imbalance means the drug will still need careful scrutiny as Roche takes the data to regulators.