New data build case for Roche's oral BTK drug for MS

Roche has said its oral BTK inhibitor fenebrutinib could become the first drug in the class to be approved for multiple sclerosis, after reporting new data from two phase 3 trials.

The results come from the previously reported FENhance 1 and 2 studies, which will be presented to clinicians at the American Academy of Neurology (AAN) congress in Chicago today and show that fenebrutinib reduced relapses and brain lesions in relapsing multiple sclerosis (RMS) patients compared to standard treatment with Sanofi's Aubagio (teriflunomide).

The two studies showed a 51.1% and 58.5% drop, respectively, in the annualised relapse rate (ARR) compared to Aubagio, but the data also showed an eight-to-one imbalance in fatalities between the active treatment and control groups that raised alarm bells, particularly as a similar pattern was seen in the accompanying FENtrepid study in primary progressive multiple sclerosis (PPMS).

At AAN, Roche revealed that the deaths with fenebrutinib arose from various causes – including infections, type 1 diabetes complications, bleeding, injury, and suicide – that suggest they are not linked to the drug treatment. The company has previously also reported that the FENtrepid deaths were assessed as unrelated to fenebrutinib.

In a statement, Roche reiterated its attention to file fenebrutinib for approval in the two forms of MS, saying that the drug could become "the first and only high-efficacy oral" for both RMS and PPMS. It has previously suggested that sales of the drug could eventually top $5 billion a year.

It added that the FENhance results equate to patients having approximately one relapse every 17 years, more than halving the relapses seen with Aubagio in the same period of time. The data also showed reduced disease activity in the brain measured using MRI scans with fenebrutinib. fewer new brain lesions, and lower levels of inflammation in the brain.

The oral BTK drug reduced markers of active inflammation by 70.7% in FENhance 1 and 77.6% in FENhance 2 compared with Aubagio, as measured by new lesions, said Roche

There was also a non-significant trend toward reduced disability progression, assessed using walking ability, upper limb function, and the Expanded Disability Status Scale (EDSS), with FENhance 1 showing a 26% improvement over Sanofi's drug and FENhance showing fenebrutinib was 20% better.

The oral BTK inhibitor race in RMS is now a two-horse affair, with fenebrutinib vying against Novartis' remibrutinib, already approved as Rhapsido for chronic spontaneous urticaria (CSU), which is in phase 3.

The FDA rejected Sanofi's tolebrutinib candidate as a treatment for non-relapsing secondary progressive MS (nrSPMS) at the end of last year, although, it has been approved in the United Arab Emirates (UAE). The drug's development for RMS and PPMS was abandoned after disappointing clinical trial results.

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

Enspryng filing for MOGAD

In other news, Roche also said it is planning to file for approval of its anti-IL-6 antibody Enspryng (satralizumab) for rare disease myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), after reporting positive data from the phase 3 METEOROID study at AAN.

If all goes well, the drug could become the first approved treatment for MOGAD, an autoimmune disease in which, like MS, the myelin sheath protecting neurons is attacked. Enspryng is already approved to treat anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD).