- Roche on Wednesday said an experimental multiple sclerosis drug it is developing met the goals of a Phase 2 trial of 109 patients with relapsing forms of the disease.
- When compared to a placebo, the drug, fenebrutinib, significantly reduced the number of “T1” brain lesions — a marker of inflammation in MS — on an imaging scan after four, eight or 12 weeks of treatment. The drug also reduced new or growing “T2” lesions, which are a sign of disease burden.
- Fenebrutinib’s safety profile was “consistent” with previous testing, Roche added, without providing specifics. Detailed findings will be presented at a future medical meeting. Fenebrutinib is already in Phase 3 testing in patients with relapsing as well as primary progressive multiple sclerosis.
Fenebrutinib is one of a class of drugs known as BTK inhibitors, which are commonly used for certain blood cancers. However, in recent years, they have emerged as potential autoimmune disease medicines as well.
Unlike their cancer-treating predecessors, these newer BTK inhibitors are meant to cross the blood-brain barrier. And because they block an enzyme that activates a variety of immune cells, they’re thought to have potential for treating multiple forms of MS, including the rarer “primary progressive” type.
Fenebrutinib’s mechanism of action “has the potential to both reduce MS disease activity, such as relapses, and also impact disease progression,” said Levi Garraway, Roche’s chief medical officer, in a statement.
Safety is a concern, though. U.S. trials of a drug Sanofi acquired through its 2020 acquisition of Principia Biopharma were stalled after the Food and Drug Administration flagged signs of liver damage. In April, the FDA also halted testing in part of a similar medicine from Merck KGaA after lab tests suggested liver injury.
Those instances “are likely a class effect,” Sanofi R&D chief Dietmar Berger said on an earnings call last month, adding that his company is working with U.S. regulators on a risk mitigation program.
Sanofi expects initial Phase 3 results either later this year or early next, Berger said. Merck KGaA has said that, even with the trial partially on hold in the U.S., late-stage results could come in the fourth quarter.
Roche is one of a few others, including Novartis and Biogen, following close behind. The company claims fenebrutinib could be superior because it is “reversible” and doesn’t form a permanent chemical bond with its target. That feature, as well as its selectivity, could lead to fewer side effects, Roche said. (Biogen’s BTK blocker is also reversible, but in Phase 1 testing.)
About 2,400 patients and healthy volunteers have been treated with Roche’s medicine to date and no new safety concerns emerged in the Phase 2 trial, the company said in its statement.
A spokesperson for Roche’s Genentech unit added that the company hasn’t observed any cases meeting the criteria of “Hy’s law,” a rough test used to gauge whether patients are at risk of serious liver damage. Liver enzyme elevations, a warning sign of potential injury, were “transient and reversible,” the spokesperson said.