Novartis lifted the veil on its phase 3 wins in relapsing multiple sclerosis (RMS) announced in early September.
Not only did the company’s BTK inhibitor Rhapsido reduce relapses and disease progression compared to Aubagio, an older RMS treatment from Sanofi, but it did so without inciting any liver issues, a side effect that has proven to be an ongoing barrier to success of the drug class in this indication.
Novartis said it plans to seek regulatory approval globally in RMS. Its applications will be backed by data from the Remodel-1 and Remodel-2 trials presented at MSToronto last week and simultaneously published in The Lancet.
Together the two trials enrolled more than 2,000 patients who received 100 mg of Rhapsido twice daily or the control treatment of 14mg of Aubagio once daily. Both trials met the primary endpoint; Rhapsido significantly lowered the annualized relapse rate compared to Aubagio by 35.2% and 31.2% respectively. According to Novartis, the improvement in Rhapsido patients translates to roughly one relapse every 13 years.
The outcome was decidedly positive, though on the “low end of expectations,” according to Jeffries analysts. William Blair analysts noticed that Rhapsido’s performance on the primary endpoint was numerically inferior to Roche’s rival BTK candidate fenebrutinib, though they cited caution in making cross-trial comparisons.
In phase 3 Fenhance 1 and 2 trials, Roche’s investigational RMS treatment fenebrutinib set a high bar, reducing annualized relapse rate by 51.1% and 58.5%, respectively, against Aubagio.
Rhapsido also demonstrated benefits beyond relapse rate. In the brain, Rhapsido reduced T2 lesion activity captured on MRI, a marker of RMS chronic disease burden, by 65% and 70% compared to Aubagio. And it reduced Gd+T1 lesions by 66% across both of the trials.
The BTK inhibitor also showed a “clinically meaningful” reduction in disease progression. Ninety-two percent of patients on Rhapsido did not experience disease progression over two years. Six-month confirmed disability progression, a measure of neurological worsening in MS, was reduced by nearly 30%—a figure which Novartis called “nominally significant” suggesting it does not bear statistical significance. At three months, Rhapsido showed the same trend with a 20.5% reduction, but the finding was again not significant.
“While nominally significant, we see this as meaningful given the unmet need around slowing disability progression in RMS,” Jeffries analysts wrote on the results.
While efficacy data came up slight by some accounts, Novartis takes the edge off with the safety data. Across the 2,000 patients enrolled in the two trials, the drugmaker saw no liver safety signals and no Hy’s Law cases, criteria used to detect patients that are at high-risk of a fatal drug-induced liver injury.
Rhapsido appears to have shaken the liver toxicity risks that have undercut other drugs in the class for years. Late last year, the FDA ultimately rejected Sanofi’s tolebrutinib as treatment for non-relapsing secondary progressive MS because trial data showed increased risk of drug-induced liver injury, including six cases of Hy’s Law in its phase 3.
And in 2023, Roche’s fenebrutinib was put on an FDA partial clinical hold after two cases of elevated liver enzymes. In Fenhance 1, Roche also reported a Hy’s Law case for its fenebrutinib arm and the Aubagio arm. Aubagio carries boxed warning for hepatoxicity on its label.
The combination of the efficacy and safety profiles, “suggest [Rhapsido] has the potential to deliver a meaningful, differentiated treatment option for people living with RMS,” said Heinz Wiendl, M.D., chair of the department of neurology and neurophysiology at the Medical Center of University of Freiburg in Germany.
Rhapsido was first approved by the FDA in 2025 as a treatment for chronic spontaneous urticaria, or chronic hives. And earlier this month, the drug secured a second FDA okay as the first-ever approved treatment for another form of chronic hives called symptomatic dermographism (SD).
Jeffries analysists said that an MS approval could bump Rhapsido peak sales to as much as $3.5 billion. The BTK inhibitor is also being tested in food allergy and hidradenitis suppurativa. These indications could boost Rhapsido sales to the high, single-digit billions.