Sanofi has announced that tolebrutinib, a BTK inhibitor, failed in two out of three Phase 3 trials. Tolebrutinib was being evaluated across two forms of chronic neurological disorder. The HERCULES trial included patients with non-relapsing secondary progressive MS, while two identical Phase 3 studies, known as GEMINI 1 and 2, were conducted on patients with relapsing-remitting MS.
The HERCULES study was a success, according to Sanofi, which revealed that tolebrutinib had performed well in the test and met its primary goal of delaying the progression of disabilities compared to a placebo.
However, in the GEMINI trials, tolebrutinib could not surpass the performance of Sanofi’s already-approved MS drug, Aubagio, in reducing the frequency of relapses over 36 months. In an attempt to find a silver lining, the company stated that after evaluating the six-month outcomes of these trials, a significant delay in the emergence of disability was observed.
Non-relapsing secondary progressive MS differs from relapsing MS, where the person experiences episodes of new or worsening symptoms, known as relapses, followed by periods of recovery, at least in part. Non-relapsing secondary progressive MS is characterized by patients who stop having relapses but continue to become more disabled in other ways, which may include fatigue, cognitive issues, and difficulty walking.
This is not the first time that tolebrutinib has encountered obstacles in a clinical setting. All three trials were placed on partial clinical hold by the FDA two years ago due to what the company described at the time as “a limited number of cases of drug-induced liver injury identified with tolebrutinib exposure.”
Even if tolebrutinib had succeeded in the GEMINI trials, the BTK inhibitor would still face a tough global market, already populated by Bristol Myers Squibb’s Zeposia, Roche’s Ocrevus, Biogen’s Tecfidera, and Sanofi’s own Aubagio.
Sanofi’s issues with the GEMINI trials are similar to those of Merck KGaA’s BTK inhibitor, evobrutinib, which caused a stir in the sector in December when it failed to outperform Aubagio in two Phase 3 trials in relapsing MS. Although Merck had previously cited the drug’s blockbuster potential, the German pharmaceutical company finally pulled the plug on evobrutinib in March.
