Novartis pill cut MS relapses more than an older drug in two big trials

A daily pill from Novartis led to fewer multiple sclerosis (MS) relapses than an older, approved MS pill in two large trials, according to results presented last month and published in The Lancet¹. The drug, called remibrutinib, was compared with Aubagio (generic name teriflunomide) in about 2,000 adults with relapsing forms of MS across 46 countries¹. Novartis says it now plans to ask regulators around the world to approve it for relapsing MS².

What happened

MS is a disease in which the immune system mistakenly attacks healthy tissue in the brain and spinal cord, causing inflammation and nerve damage¹. In relapsing MS, people have relapses: periods of new or worsening symptoms¹. Over time, nerve damage can add up to worsening disability¹.

The two trials, named REMODEL-1 and REMODEL-2, were Phase 3 trials, the final large tests usually done before a company seeks approval¹. Full results were presented at the 10th joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, and detailed in a paper in The Lancet¹. Novartis had already announced that both trials met their main goal².

Remibrutinib is a tablet that blocks an enzyme called Bruton’s tyrosine kinase, or BTK¹. That enzyme helps drive inflammation in certain immune cells, including B cells and microglia, the brain’s own immune cells¹. Unlike some other MS treatments, BTK blockers do not work by wiping out B cells, which also help the body fight infections¹.

The evidence so far

Each trial was randomized and double-blind: people were assigned by chance to one drug or the other, and neither they nor their doctors knew which they got³⁴. The trials also used a “double-dummy” design, meaning each person took both a real pill and a look-alike dummy so the two treatments could not be told apart³⁴. REMODEL-1 enrolled 1,000 people and REMODEL-2 enrolled 1,007, according to the trial registry³⁴. Participants were aged 18 to 55¹.

People took either remibrutinib, 100 mg twice a day, or Aubagio, 14 mg once a day, for up to 30 months (two and a half years)¹. The main question was whether remibrutinib cut the yearly relapse rate more than Aubagio¹.

• Relapses: In REMODEL-1, the estimated yearly relapse rate was 0.073 on remibrutinib versus 0.112 on Aubagio, a 35.2% reduction¹. In REMODEL-2 it was 0.080 versus 0.116, a 31.2% reduction¹. Put another way, on either drug relapses were uncommon, roughly one per 9 to 14 years of treatment on average, and fewer on remibrutinib.
• Brain scans: Remibrutinib reduced the yearly rate of new or growing MS spots on MRI scans by 65.3% in REMODEL-1 and 70.3% in REMODEL-2, compared with Aubagio¹. Spots showing active inflammation on each scan fell by about 66% in both trials¹.
• Disability: People on remibrutinib had a 29.2% lower risk of disability getting worse and staying worse for at least six months¹. More than 92% of people on remibrutinib stayed free of this kind of worsening over two years¹.

Novartis said the drug beat Aubagio on the main goal and on “all key secondary endpoints,” the other main measures the trials set out to check².

What the trials showed about side effects

Side effects of any kind were reported in 79.5% of people on remibrutinib and 81.5% of people on Aubagio¹. Serious side effects happened in 6% and 7%, respectively¹. Nearly 50% fewer people on remibrutinib stopped treatment because of side effects than people on Aubagio¹. Novartis said the safety findings were in line with what it had seen in other trials of the drug².

What it does not show yet

The disability result is the weakest part. It reached the usual bar for statistical significance, but not the stricter bar used when a trial tests many outcomes at once¹. That means it hints at a benefit but does not firmly show that remibrutinib slows disability¹. Novartis described the effect as a “clinically meaningful” delay in disability getting worse². Readers should weigh both descriptions.

Other limits follow from how the trials were built:

• The comparison was with Aubagio only³⁴. The trials do not tell us how remibrutinib compares with other MS drugs.
• The main comparison lasted up to 30 months³⁴. Effects and side effects over many more years are not yet known, though both trials continue with an open-label phase, where everyone knowingly takes remibrutinib³⁴.
• The trials included adults aged 18 to 55 with relapsing MS¹. They do not show how the drug works in older people or in progressive forms of MS without relapses.
• The registry had not yet posted results at the time of writing³⁴.

Who is behind it

Novartis sponsored both trials³⁴. The company’s chief medical officer, Shreeram Aradhye, said in its announcement of the main results:

“The positive REMODEL results underscore the potential of remibrutinib as a high-efficacy oral therapy for people living with RMS with a differentiated benefit-risk profile.”²

The drug matters a great deal to Novartis commercially. Remibrutinib is already approved in the US, the EU and Japan, under the brand name Rhapsido, for chronic spontaneous urticaria, a long-lasting form of hives². It brought in a little over $100 million in sales in the first half of the year, and analysts have forecast peak yearly sales of $3 billion to $9 billion across its uses². Novartis is also testing it in other immune and nerve conditions, including food allergies and generalized myasthenia gravis².

Aubagio, the comparison drug, was once a $2.3 billion-a-year seller and lost patent protection in the US and Europe in 2023².

How it fits the field

BTK blockers are thought to reduce the inflammation that drives relapses¹. Researchers also hope they may reduce the slower, ongoing inflammation that can worsen disability even when no relapses happen¹. Because they do not drain the body of B cells, they may offer advantages for long-term use, though that is a hope rather than a finding from these trials¹.

Novartis is testing that second idea separately. A trial called REMASTER is comparing remibrutinib with a placebo (a dummy pill) in adults with secondary progressive MS, a form in which symptoms slowly worsen, who have had no relapses in the past two years⁵. The trial listing seeks 1,275 participants, with a blinded phase lasting up to about five years⁵.

What to watch next

• Approval filings: Novartis says it will file with regulators worldwide for relapsing MS². No decision dates have been reported.
• Longer follow-up: The open-label extensions of both trials should show how people fare on the pill over a longer time³⁴.
• Progressive MS: Results from REMASTER will test whether the drug helps people whose MS worsens without relapses⁵.