After heralding data last month showing that the multiple sclerosis candidate fenebrutinib may have crossed the blood-brain barrier, Genentech revealed quietly last week that the program has been placed on a partial clinical hold by the FDA in the U.S.
In an update posted Thursday, Nov. 30, the Roche unit said that the FDA placed fenebrutinib’s clinical program on partial hold as a result of two recent cases of elevated liver enzymes. The cases were discovered in the phase 3 FENhance relapsing multiple sclerosis (RMS) studies, according to the update. The patients did not experience symptoms and have returned to normal levels after treatment was discontinued.
But the cases were enough to get the attention of the FDA. Genentech said that new enrollment in the U.S. is now paused for the FENhance I program. FENhance II in RMS and FENtrepid for primary progressive MS are already fully enrolled. U.S. patients who have received the study drug for more than 70 days will continue in all of the studies.
But Genentech said that a small number of patients who had not received the study drug for that long will have to discontinue treatment.
“Patient safety is Genentech’s highest priority, and we are working closely with the independent data monitoring committee, and investigators around the world,” Genentech said. The company noted that 2,500 patients have received fenebrutinib across the phase 1 through 3 programs in several diseases including MS and other autoimmune disorders.
Outside the U.S., Genentech has trial sites for the studies in the U.K., Europe, South America, Central America, Asia, Africa, Australia, Canada and Russia, according to the clinical trial record for fenebrutinib.
The therapy is an oral Bruton’s tyrosine kinase (BTK) inhibitor that is meant to block the function of BTK, which regulates B-cell development and activation but is also involved in the activation of the innate immune system.
In October, Roche touted fenebrutinib’s "best in disease" potential with phase 2 data from the FENopta study in RMS that showed 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.
On a secondary endpoint of T2 lesions, there was a relative reduction of 95% in the same period. The company also said the therapy crossed the blood-brain barrier, a difficult feat for any drug.