The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted positive opinions for drugs to treat two neurological diseases. Cenrifki (tolebrutinib, Sanofi Winthrop) was recommended for the treatment of nonrelapsing secondary progressive multiple sclerosis (MS). Itvisma (onasemnogene abeparvovec, Novartis Europharm Limited) was greenlit for the treatment of spinal muscular atrophy (SMA).

The active ingredient in Cenrifki is tolebrutinib, a Bruton tyrosine kinase (BTK) inhibitor. The BTK enzyme is essential for the survival and activation of B cells, which are believed to be involved in the inflammation caused by MS. It also regulates macrophages and microglia in the brain, which are also linked to MS progression. Although the precise mechanism by which tolebrutinib exerts its therapeutic effect in MS is not fully understood, it is thought to inhibit the activation of B cells, macrophages, and microglia in the periphery and the central nervous system. In turn, this prevents the MS activity that leads to relapses and slows down longer-term damage to nerve cells.

In granting a marketing authorization, the CHMP referenced the HERCULES study, a phase 3, double-blind, placebo-controlled trial where participants with nonrelapsing secondary progressive MS received tolebrutinib (60 mg once daily) or placebo. The researchers found that patients who received tolebrutinib had a 30.7% reduction in the risk of 6-month confirmed disability progression and a 38% reduction in the adjusted mean number of new and/or enlarging T2-hyperintense lesions per year compared with patients given placebo.

Cenrifki will be available as 60 mg film-coated tablets and is indicated for adult patients without relapses in the last 2 years.

The most common side effects are infections, petechiae, increased tendency to bruise, heavy menstrual bleeding, abdominal pain, contusion, and increased levels of liver enzymes. A side effect of concern is drug-induced liver injury.

Gene therapy Itvisma was also recommended for the treatment of 5q spinal muscular atrophy with a biallelic mutation in the SMN1 gene in patients 2 years of age and older.

The active substance of Itvisma is onasemnogene abeparvovec, which acts as a gene replacement therapy delivering a healthy, functional copy of the SMN1 gene directly into the nucleus of motor neuron cells, thereby addressing the root cause of the disease. Itvisma is delivered via a single, one-time intrathecal injection.

In granting a marketing authorization, the CHMP acknowledged the phase 3 STEER trial, which demonstrated how treatment with intrathecal onasemnogene abeparvovec improved motor function in children aged 2 years and older with SMA who have biallelic mutation in the SMN1 gene.

Itvisma will be available as a 1.2 x 1014 vector genomes solution for injection. 

The most common side effects with include upper respiratory tract infection, pyrexia, vomiting, headache, and increased hepatic enzymes.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.