Although the drug has not yet been approved by the U.S. Food and Drug Administration (FDA), a recently completed phase 2B trial, published in the September 2021 issue of The Lancet Neurology, revealed that it effectively reduces new, active brain lesions in people with RMS — either relapsing-remitting MS or active secondary-progressive MS — particularly at a dose of 60 milligrams (mg) per day. The trial also found that the drug is safe and has minimal side effects, the researchers say. “Based upon this trial’s findings, 60 mg is the chosen dose for phase 3 trials,” says study coauthor Robert J. Fox, MD, vice chair for research at the Cleveland Clinic Neurological Institute in Ohio. “The side effect profile was similar between placebo and active treatment, which is encouraging, particularly for a drug with such a marked effect on [brain lesions],” says Dr. Fox. RELATED: MS Medications
How BTK Inhibitors Work
Tolebrutinib joins evobrutinib in the emerging BTK inhibitor class of drugs. Both of these oral medications — they are taken daily, in pill form — are still being evaluated in clinical trials. Research to date suggests they work by limiting production of Bruton’s tyrosine kinase in the body. BTK plays a role in the development of B cells, a type of white blood cell involved in the human immune system.
Multiple Doses Evaluated in Phase 2B Tolebrutinib Trial
In the phase 2B trial of tolebrutinib — new drugs must pass through at least three phases of clinical trials to receive FDA approval — Fox and his colleagues evaluated the drug in 130 adults ages 18 to 55 years with RMS at four dosing levels: 5, 15, 30, and 60 mg. Participants received the drug daily for 12 weeks, either before or after four weeks of treatment with placebo, a medication that has no clinical effect. They underwent magnetic resonance imaging (MRI) scans at the start of the study and then every four weeks over 16 weeks. After 12 weeks of treatment with the drug, all 126 participants who completed the study saw reductions in the number of brain lesions seen on MRI, with the most significant drop in lesions seen with the 60-mg dose.
Headache the Most Common Side Effect of Tolebrutinib
The most common nonserious side effect experienced during tolebrutinib treatment was headache — in 1 of 33 participants in the 5-mg dose group; 3 of 32 in the 15-mg dose group; 1 of 33 in the 30-mg dose group; and 4 of 32 in the 60-mg dose group. Only one participant experienced a serious side effect (an MS relapse), at the 60-mg dose, which required hospital treatment, the researchers said. RELATED: Side Effects of Multiple Sclerosis Medications
Tolebrutinib Also Being Studied for Progressive MS
According to Fox, tolebrutinib is already being evaluated in phase 3 trials for both RMS and progressive MS. “This early data suggests that tolebrutinib is very effective in reducing MRI disease activity in RMS and has a favorable safety profile,” Fox notes. “It penetrates the central nervous system, so it has the potential to have benefits on pathologic processes within the brain, including those related to progressive MS.”
