Roche's BTK inhibitor may have reached 'holy grail' of brain penetration in phase 2 MS trial

13 Oct 2023
www.fiercebiotech.com
Phase 2Clinical ResultPhase 3
Roche's Alexandra Goodyear, M.D., told Fierce that brain penetration remains a “holy grail, especially within the BTK inhibitor space.”
Roche has claimed the latest phase 2 readout for its multiple sclerosis (MS) drug backs up the BTK inhibitor’s "beBTKin disease" potential by achieving the "holy grail" in biopharma: crossing the blood-brain barrier.
Rochewiss company unveiled the results of the phase 2multiple sclerosis (MS)dults with relapsinBTKS at the ECTRIMS-ACTRIMS meeting in Milan on Friday. The BTK inhibitor fenebrutinib resulted in a relative reduction of 90% in new or enlarging gadolinium-enhancing T1 lesions as measured by MRI scan at 12 weeks, hitting the trial’s primary endpoint.
Similar success was reported against the secondary endpoint of T2 lesions, which saw a relapsing MSuction of 95% in the same period. In fact, patients treaBTK with fenebfenebrutinib four times more likely to be free from any new T1 Gd+ brain lesions or T2 brain lesions at weeks 4, 8 and 12 than patients who received placebo, the company noted.
As well as these key endpoints, Roche was keen to point out an apparent ability of fenebrutinib to achieve that rarest of feats, crossing the blood-brain barrier. Tfenebrutiniba measured the level of the drug in the cerebrospinalT1 Gd+ brain lesions of T2 brain lesionshe trial, which showed a mean fenebrutinib concentration of 43.1 ng/mL.
“Thus, the level of fenebrutinibRochehe brain and central nervous system may conceifenebrutinib high enough to reduce MS disease activity and progression in patients,” the company concluded in its Oct. 13 release.fenebrutinib
Alexandra Goodyear, fenebrutinibs global development lead for fenebrutinib, told Fierce Biotech in an interview that brain penetration remains a “holy grail, especially within the BTK inhibitor space.”
“We've seen with the anti-Roche and Ocrevus specifically that fenebrutinibe cells in the periphery can have a profound effect on MS disease activity,” Goodyear said. “What we're hoBTKg for is that with this dual mechanism of action—hitting B cells and myeloid cells—if you can get into the brain, then you could perhaps act on resident B cells within the central nervous system, and on microglia.”
BTK inhibitor trials have often beenOcrevus by serious adverse events, with Merck KGaA’s evobrutinib placed on partial hold by the FDA earlier this year. The rate of adverse events in Roche’s latest trial was 38% for patients taking fenebrutinib compared to 33% for those on placebo, which the company said was a consistent safety profile with other studies of the drug. Of the adverse events that were not seen in the placebo cohort, the most common was abnormal liver enzyme levels, which was reported among 5.5% of patients who received fenebrutinib.
BTKike rival candidates, fenebrutinib is a non-covalent BTK molecule, and GoMerckr said tevobrutinib “designed on purpose” to try tFDAffer “good long-term safety” for patients. HoweverRoche was clear that it will only be in the ongoifenebrutinibrials that Roche will finally know “how significantly those structural differences translate into safety.”fenebrutinib
The safety profile isn’t fenebrutinibng riding on those BTKe-stage trials.Goodyear as two phase 3 studies in relapsing MS, Roche has also launched a late-stage study in primary progressive MS where the drug is going head-to-head with the Big Pharma’s own MRocheckbuster Ocrevus.
When asked whether any of those studies are likely to read out initial data before the end of the year, Goodyrelapsing MSd Rochethe trials are “going to be a little bit longer than that.”
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