Tolebrutinib associated with long-term safety, efficacy in relapsing-remitting MS

Key takeaways:

• No new safety signals or serious adverse events were reported.
• Of 124 participants who received tolebrutinib 60 mg/day for at least 8 weeks, ARR was 0.20, and 73.4% remained relapse free.

BOSTON — Treatment with tolebrutinib 60 mg per day was safe and associated with low annualized relapse rate and stable disability through 120 weeks, according to research presented at the American Academy of Neurology annual meeting.

“In the MS field, we need treatments that can better target both peripheral and centrally mediated inflammation, and I think there is a lot of hope for [Bruton’s tyrosine kinase] inhibitors,” Jiwon Oh, MD, PhD, associate professor at the University of Toronto and medical director of the Multiple Sclerosis Program at St. Michael’s Hospital, told Healio.

Oh and colleagues assessed the safety and efficacy of tolebrutinib — a Bruton’s tyrosine kinase inhibitor — at week 120 in a phase 2b long-term safety extension, as the investigational brain-penetrant previously was well-tolerated in patients with relapsing-remitting MS.

The extension study included 107 patients and was conducted in two parts: In part A, participants continued their original tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until phase 3 study dose selection (60 mg/day), and in part B, participants received open-label tolebrutinib (60 mg/day).

Outcomes of interest included annualized relapse rate and change in Expanded Disability Status Scale score from baseline, with safety assessed by adverse events.

According to results, no new safety signals were reported at week 120. Researchers also reported no tolebrutinib dose effect for treatment-emergent adverse effects or serious adverse events in part A, nor emerging safety signals for those who switched to 60 mg per day in part B.

For the 124 participants who received tolebrutinib 60 mg per day for at least 8 weeks, ARR was 0.20 (95% CI, 0.14-0.28) and 73.4% remained relapse free, with mean EDSS stable through week 120.

The most common reported treatment-emergent adverse events included COVID-19 (24.8%); headache (13.6%); nasopharyngitis (12.8%); upper respiratory tract infection (11.2%); bacterial cystitis, arthralgia and back pain (7.2% each); and pharyngitis (6.4%).

“So far, tolebrutinib seems pretty well-tolerated based on the extension study because the majority of people after 120 weeks are still in the study,” Oh said. “It seems to have a good effect on lowering the annualized relapse rate, keeping disability stable. ... The phase 3 trial results will be important to consolidate these findings.”