Experimental MS pill cuts relapses in two major trials

An experimental pill for multiple sclerosis cut relapse rates by about a third compared with the approved drug Aubagio in two late-stage trials.

Remibrutinib also reduced brain lesion activity, while findings suggested a possible benefit in slowing disability progression.

The REMODEL-1 and REMODEL-2 trials involved approximately 2,000 adults aged 18 to 55 across 46 countries, comparing remibrutinib with the approved multiple sclerosis (MS) treatment Aubagio (teriflunomide).

Developed by Novartis, remibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor. It blocks an enzyme involved in inflammation within immune cells, including B cells and microglia.

Unlike some existing MS treatments, it is designed to reduce inflammation without continuously depleting B cells, which also help protect the body against infections.

MS occurs when the immune system mistakenly attacks healthy tissue in the brain and spinal cord, causing inflammation and nerve damage that can lead to worsening disability.

Heinz Wiendl, professor of neurology at the University of Freiburg, said: “The REMODEL trial results showed that oral remibrutinib delivered a significant reduction in relapse activity while also showing a clinically meaningful effect on confirmed disability progression in people living with relapsing MS.”

The trials assessed whether remibrutinib could reduce relapses, periods of new or worsening symptoms, more effectively than Aubagio.

Participants were randomly assigned to receive either 100mg of remibrutinib twice daily or 14mg of Aubagio once daily, with follow-up lasting up to 30 months.

Both trials met their primary objective of reducing annual relapse rates.

In REMODEL-1, the estimated annual relapse rate was 0.073 among participants taking remibrutinib, compared with 0.112 among those receiving Aubagio, a reduction of 35.2 per cent.

Results were similar in REMODEL-2, where the respective rates were 0.080 and 0.116, representing a 31.2 per cent reduction.

MRI scans also showed less disease activity among participants receiving remibrutinib.

The annual rate of new or enlarging lesions, areas of damage visible on brain scans, was reduced by 65.3 per cent in REMODEL-1 and 70.3 per cent in REMODEL-2 compared with Aubagio.

The number of lesions showing active inflammation per scan was also reduced by approximately 66 per cent in both trials.

Researchers also examined whether remibrutinib could slow disability progression.

Participants taking the drug had a 29.2 per cent lower risk of six-month confirmed disability progression compared with those receiving Aubagio.

This measures worsening disability that remains present for at least six months.

More than 92 per cent of participants receiving remibrutinib remained free from this form of disability progression over two years.

However, the 29.2 per cent risk reduction was only nominally statistically significant. Although it met the usual threshold for statistical significance, it did not meet the stricter requirements applied when a trial assesses multiple outcomes.

The findings therefore suggest a possible benefit but do not conclusively establish that remibrutinib slows disability progression.

The trials also assessed safety and tolerability.

Adverse events were reported in 79.5 per cent of participants receiving remibrutinib and 81.5 per cent of those taking Aubagio.

Serious adverse events occurred in 6 per cent and 7 per cent of participants respectively.

Fewer participants stopped treatment because of adverse events in the remibrutinib group, at 3.1 per cent compared with 5.8 per cent in the Aubagio group.

Researchers also assessed liver safety, as marked increases in liver enzymes can indicate possible liver injury and have been reported with several BTK inhibitors.

Such increases occurred in 2 per cent of participants taking remibrutinib, compared with 7.4 per cent of those receiving Aubagio.

No cases met established criteria for potentially serious drug-related liver injury.

Following the results, Novartis plans to submit regulatory applications worldwide seeking approval for remibrutinib as a treatment for relapsing forms of MS.

The trials demonstrated reductions in relapse rates and brain lesion activity compared with Aubagio, while the effect on disability progression remains less certain.