Dive Brief:
- Roche’s experimental pill fenebrutinib hit its main goal in a second Phase 3 trial in the most common form of multiple sclerosis, helping treatment recipients experience significantly fewer relapses than study volunteers who got Sanofi’s Aubagio, the company said Monday.
- However, Roche also reported a case of severe liver side effects in one enrollee who got fenebrutinib in the study. It also revealed a higher number of deaths among people who took its therapy in the two Phase 3 trials in relapsing MS, which prompted one analyst, Michael Leuchten of Jefferies, to question the drug’s approval prospects. Analysts have forecasted peak sales of more than 3 billion Swiss francs, or $3.8 billion, for fenebrutinib, Leuchten wrote.
- Fenebrutinib is part of a new crop of “BTK inhibitors” that drugmakers are now positioning as potential autoimmune disease treatments. The effort has yielded multiple setbacks in MS, though, as the Food and Drug Administration recently rejected a BTK drug from Sanofi, and other developers like Merck KGaA and Biogen have given up on prospective drugs.
Dive Insight:
BTK, or “Bruton’s tyrosine kinase” inhibitors, have proven successful at treating blood cancers like leukemia and lymphoma. But they’ve been seen as helping with autoimmune conditions, too, as they work by suppressing the activity of the B cells that go haywire in those diseases. Other B cell-targeting therapies, like Roche’s Ocrevus and Novartis’ Kesimpta, have helped people with MS control relapses and disability progression.
Some BTK drugs have already made inroads against immunological disorders. Sanofi’s Wayrilz and Novartis’ Rhapsido have been approved in immune thrombocytopenia and a form of hives, respectively. But progress has been slower-going against MS. Sanofi appeared poised to bring its drug, tolebrutinib, to market for a less common form of the disease. But the rejection it received was based around the kind of liver concerns that now hang over fenebrutinib.
Roche reported Monday that in a trial called “FENhance 1,” people with the relapsing form of the disorder who got fenebrutinib had a 51% lower yearly relapse rate than those who got Aubagio over the course of at least 96 weeks. That result was consistent with findings from an earlier trial in relapsed disease, “FENhance 2.” Roche said the combined results “equate to approximately one relapse every 17 years.” The drug also succeeded in another study in primary progressive disease.
However, in FENhance 1, Roche said there was one case in the fenebrutinib group, along with one in the Aubagio group, of liver enzyme elevations that met a threshold called “Hy’s law.” That threshold equates to an increased risk of death or liver transplantation, and often draws attention from U.S. drug regulators.
Additionally, in the combined FENhance 1 and 2 populations, there were eight deaths among fenebrutinib recipients “with various causes and at different points in treatment,” compared with one in Aubagio-treated patients. “Further analyses are ongoing to better understand these findings,” Roche said in a statement.
The new findings, then, may not help fenebrutinib’s already shaky case to the Food and Drug Administration, Leuchten wrote in a note to clients. Liver-related side effects were already a known issue from earlier fenebrutinib studies as well as trials of other BTK inhibitors. But the imbalance in patient deaths is a new finding that will likely stimulate further scrutiny, he wrote.
“The tolebrutinib [rejection letter] makes clear the FDA is looking at a risk/balance profile especially if treatment alternatives are available,” he wrote. “Combined with the liver safety we are not sure the fenebrutinib profile clears the bar.”
