Merck KGaA’s foray into the competitive BTK inhibitor space has hit a roadblock, with its highly-touted contender, Evobrutinib, failing to surpass Sanofi’s Aubagio in two pivotal phase 3 clinical trials.
This unexpected turn of events has not only sent ripples through the pharmaceutical landscape but also prompted a reevaluation of the viability of other heavily supported candidates in the quest for effective multiple sclerosis (MS) treatments.
BTK inhibitors, celebrated for their potential in addressing smoldering MS—a condition marked by chronic inflammation linked to symptom progression in seemingly stable patients—have drawn major players into the fray. Sanofi’s strategic move to acquire Principia Biopharma for a substantial $3.7 billion set the stage, with Biogen, Novartis, and Roche also making significant strides, ushering their candidates into the critical phases of clinical trials.
Merck’s recent release of phase 3 data for Evobrutinib has cast a shadow of uncertainty over the BTK inhibitor landscape. In two pivotal trials focusing on patients with relapsing multiple sclerosis, Evobrutinib failed to demonstrate superiority over the control drug, Aubagio, in terms of annualized relapse rates (ARR). Both trials, evolutionRMS 1 and evolutionRMS 2, reported almost identical ARRs, with neither meeting the primary endpoint for up to 156 weeks.
The disappointing results have left Merck’s pipeline prospect hanging in the balance, and the company’s official statement offered scant consolation, devoid of any silver linings. Just last month, Merck had laid out ambitious plans for a major commercialization push for Evobrutinib, anticipating heightened costs starting in the fourth quarter. The consideration of using a voucher to expedite FDA review underscored the company’s confidence in the drug’s potential.
However, with the phase 3 data dashing Merck’s hopes, concerns are reverberating through other pharmaceutical firms poised for their own phase 3 readouts. Sanofi, a key contender in the BTK inhibitor space, is on track to complete phase trials of its candidate, tolebrutinib, by April. Roche and Novartis are entrenched in the race, with phase 3 trials expected to conclude in 2025 and 2026, respectively.
This setback echoes the skepticism Principia Biopharma faced before Sanofi’s acquisition, with a short seller labeling the BTK inhibitor approach as “misguided.” While efficacy concerns have momentarily taken a backseat, safety issues have emerged. The FDA’s imposition of partial holds on BTK inhibitors, in response to queries about potential liver injury associated with this class of drugs, adds a layer of complexity to an already intricate landscape.
As the dust settles from Merck’s unexpected results, the future of BTK inhibitors in the MS treatment landscape remains uncertain. The once vibrant landscape of pharmaceutical innovation is now grappling with the sobering reality that the journey toward groundbreaking therapies is fraught with challenges. The setbacks experienced by even the most promising candidates underscore the resilience required in navigating the complex terrain of drug development.
