AAN 2026: Fenebrutinib outperforms Aubagio for treating relapsing MS

The experimental drug fenebrutinib was shown to significantly outperform Aubagio (teriflunomide), an approved therapy, in reducing relapses and MRI markers of disease activity in people with relapsing forms of multiple sclerosis (MS).

That’s according to new data from a pair of largely identical Phase 3 clinical trials testing the oral BTK inhibitor globally in adults ages 18-55 with the progressive disease.

Findings from the FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) studies showed  that patients treated with fenebrutinib had relapse rates equating to about one relapse every 17 years — representing a more than 50% reduction compared with Aubagio. The therapy also showed a trend toward reducing disability progression, according to the researchers.

The results were presented by Jiwon Oh, MD, PhD, a neurologist at the University of Toronto, at the American Academy of Neurology 2026 annual meeting, which took place April 18-22 in Chicago and online.

“Fenebrutinib is the first BTK inhibitor to show clear efficacy on relapsing disease biology versus an active comparator,” Oh said during her late-breaking presentation,which was titled “Efficacy and Safety of Fenebrutinib vs Teriflunomide in Relapsing Multiple Sclerosis: Results of the FENhance 1 and 2 Studies.” Several of the study’s authors are employed by fenebrutinib’s developer Genentech or its parent company Roche.

Earlier data from another Phase 3 trial, dubbed FENtrepid (NCT04544449), have also shown that fenebrutinib is at least as effective as the approved therapy Ocrevus (ocrelizumab) at slowing confirmed disability progression in people with primary progressive MS (PPMS).

According to Oh, these findings together support the medication’s use across multiple forms of the disease.

“Taking into account the recent reported results from the FENtrepid trial in PPMS, it seems that fenebrutinib is the first and only oral treatment option to demonstrate efficacy across the entire MS disease continuum,” said Oh, who serves as medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital.

Trials data will support submissions seeking regulatory approval

Genentech is now planning to submit data from the FENhance and FENtrepid trials to regulatory agencies to seek fenebrutinib’s approval for these indications, the company said in a press release.

An oral therapy, fenebrutinib is designed to decrease the activity of certain immune cells, particularly B-cells and microglia, which are known to contribute to disease inflammation in both relapsing and progressive forms of MS. It works by targeting the BTK enzyme, which is essential for the activity of these cells.

The FENhance trials together enrolled more than 1,500 adults with relapsing forms of MS, who were randomly assigned to receive either fenebrutinib twice daily or Aubagio once daily for 96 weeks, or about two years.

The main goal was to assess if fenebrutinib could significantly reduce relapse rates over a two-year period, and previous data shared by Genentech showed that both trials met that goal. However, detailed results and data from secondary outcomes had not been disclosed yet.

Now, Oh showed that participants receiving fenebrutinib in FENhance 1 experienced 0.061 relapses per year during the trial, a 51.1% reduction compared with the 0.125 relapses per year experienced by people on Aubagio. Results were similar in FENhance 2, with relapse rates at 0.054 with fenebrutinib and 0.13 with Aubagio, representing a 58.5% reduction with the experimental therapy.

By more than doubling the time without relapses compared to [Aubagio], fenebrutinib may offer patients years of relapse-free living, thereby preserving both daily independence and long-term function.

Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said the data show the medication’s potential to benefit people with relapsing forms of MS.

“By more than doubling the time without relapses compared to [Aubagio], fenebrutinib may offer patients years of relapse-free living, thereby preserving both daily independence and long-term function,” Garrraway said.

More deaths seen with use of fenebrutinib than Aubagio

MRI scans also showed a marked reduction in disease activity in both trials, with patients given fenebrutinib having 70.7%-77.6% fewer lesions with active inflammation and 76%-82.5% fewer new or enlarging brain lesions than those on Aubagio.

The research team also assessed a composite measure of confirmed disability progression, or cCDP, as a secondary trial endpoint. This is defined as an increase in Expanded Disability Status Scale (EDSS) scores, or a 20% or greater worsening in hand or walking function, that is sustained for at least 12 weeks, or about three months.

While no significant differences were observed in each trial alone, pooled data from the two trials “demonstrated a consistent trend toward favoring fenebrutinib,” Oh said.

Still, there were seven deaths due to side effects in the fenebrutinib groups versus one in the Aubagio group. Oh noted that these deaths occurred due to several different causes, with two deaths caused by infections that were deemed related to treatment. There were also complicating factors in those two patients: One had a fungal pathogen that can cause serious infection, and the family declined recommended medical care for the other participant.

“Reassuringly, there was no clustering suggesting that this was something related to the mechanism of action of fenebrutinib,” Oh said.

BTK inhibitors such as fenebrutinib can negatively affect the liver, causing levels of liver enzymes to rise. While these elevations did occur with fenebrutinib, they resolved after treatment discontinuation and were comparable to the levels seen in the Aubagio group, the data showed.

“For the first time, a BTK inhibitor has demonstrated superiority in reducing relapses and formation of new brain lesions with comparable rates of liver enzyme elevations to a long-standing first-line medication in multiple Phase [3] RMS trials,” Oh said.