FDA starts review of Roche’s multiple sclerosis pill

• The Food and Drug Administration has accepted an approval application for Roche’s experimental multiple sclerosis pill fenebrutinib, kickstarting a review of the treatment in two forms of the disease.
• The agency will begin evaluating fenebrutinib in both the “relapsed” and “primary progressive” types of MS, positioning the treatment to possibly become the first of its kind approved in both settings. Roche didn’t say when a decision might come, though the agency has initiated a “priority review” that has a six-month timeline.
• Roche’s application is based on a trio of late-stage studies that met their main objectives. However, an imbalance in the number of deaths observed among treatment recipients and regulators’ pre-existing concerns about the liver safety of drugs like fenebrutinib could complicate the company’s approval chances.

Fenebrutinib is among a class of drugs known as BTK, or Bruton’s tyrosine kinase, inhibitors. Earlier versions of these therapies initially came to market as cancer treatments. Newer prospects are now being tested against a range of autoimmune disorders.

So far, research has produced somewhat mixed results. Novartis’ Rhapsido and Sanofi’s Wayrilz have both been approved over the last year or so for certain immune disorders. But MS has proven a more complicated target.

Development of candidates from Merck KGaA and Sanofi were both slowed by the occurrence of liver-related side effects. Both drugs also missed their goals in large trials in relapsed disease. Sanofi’s medicine, Cenrifki, was rejected in the U.S. in part because of safety concerns and cleared in Europe in June for a narrower group of MS patients.

Fenebrutinib, by contrast, hit its goals in late-stage testing. But its path to approval was slowed by a partial clinical hold — and other possible safety worries cropped up in testing, too.

In one trial, Roche reported a case of liver enzyme elevations meeting a threshold called “Hy’s law,” which indicates an increased risk of death or liver transplantation. Additionally, there were eight deaths combined among fenebrutinib recipients in two of the three Phase 3 studies, versus one death in a participant who received a comparator drug called Aubagio.

Roche, for its part, said in its statement that the deaths “occurred at different timepoints and had various causes.” The company also referred to the drug’s safety profile as “manageable” across its entire development program, which consists of a “large safety database including more than 2,700 study participants.”

https://www.biopharmadive.com/news/roche-fenebrutinib-ms-fda-accept-application-btk/831746/