InnoCare Pharma: A peer drug’s relapse control falls short of expectations. Why does this reinforce orelabrutinib’s progressive multiple sclerosis strategy?

What threshold did remibrutinib’s efficacy fall short of?

In Novartis’s phase III REMODEL-1/2 trials in relapsing multiple sclerosis (RMS), remibrutinib reduced the annualized relapse rate by 31%–35% compared with teriflunomide. The results were statistically significant, but fell short of the investor threshold of more than 40% cited by Goldman Sachs before the data release.
The competitive benchmark for relapse control is also higher: Roche’s fenebrutinib reduced the annualized relapse rate by 51%–59% in another set of phase III trials; ofatumumab achieved a reduction of approximately 50%–58% against the same comparator. These data come from different trials and should be compared cautiously, but Goldman Sachs concludes that BTK inhibitors are more likely to become an additional oral option and are unlikely to change the standard of care for RMS at their current level of efficacy.

Another clue is disability progression: a pooled analysis of remibrutinib showed a 29.2% reduction in the risk of disability progression confirmed over 6 months, below the pre-release expectation of 35%–45%. However, Goldman Sachs believes this benefit, together with the strong suppression of disease activity seen on MRI, supports the drug’s activity in the central nervous system.
Treatment needs in progressive multiple sclerosis are more focused on slowing the accumulation of disability, rather than solely reducing relapses. Physician feedback cited by Goldman Sachs suggests that these patients have greater unmet needs and that BTK inhibitors, which act through the central nervous system and modulation of microglia, may have more room to provide therapeutic benefit.
Safety was a strength of the data: there were no Hy’s Law cases or meaningful liver safety signals. However, the reduction in disability progression risk remained below previous expectations, and longer follow-up is needed to assess the durability of the benefit.

Remibrutinib and InnoCare Pharma’s orelabrutinib are both irreversible, covalent BTK inhibitors; fenebrutinib, which demonstrated stronger relapse control, is a reversible, non-covalent drug. Goldman Sachs sees the new data as supporting InnoCare Pharma and Zenas’s focus on progressive multiple sclerosis, while acknowledging the limitations of cross-trial comparisons.
Global phase III trials of orelabrutinib in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) have both begun. Goldman Sachs believes its ultimate differentiation will be determined by the magnitude and robustness of the benefit in delaying disability progression in its own trials; data from peer drugs support the direction, while the key efficacy question remains for these two trials to answer.