Trial results for the GEMINI 1 study (NCT04410978) investigating tolebrutinib (SAR442168) for relapsing forms of multiple sclerosis (RMS) were posted on ClinicalTrials.gov on 2025-06-18. The study showed that tolebrutinib 60 mg resulted in an annualized relapse rate (ARR) of 0.130 relapses per participant year, which was not significantly different from the 0.122 relapses per participant year observed with teriflunomide 14 mg (relative risk: 1.061, 95% CI: 0.808 to 1.393, p=0.6691).
Background
The GEMINI 1 study aimed to assess the efficacy and safety of tolebrutinib in participants with relapsing forms of multiple sclerosis.
Trial design
The GEMINI 1 study (NCT04410978) was a Phase 3, randomized trial that enrolled 974 participants with relapsing forms of multiple sclerosis. The study compared daily oral doses of tolebrutinib 60 mg against daily teriflunomide 14 mg (Aubagio). The primary objective was to assess the efficacy of tolebrutinib compared to teriflunomide, measured by the annualized adjudicated relapse rate (ARR).
Key results
The trial results for the primary and key secondary endpoints demonstrated the following:
- Annualized Relapse Rate (ARR): Tolebrutinib 60 mg showed an ARR of 0.130 relapses per participant year, compared to 0.122 for teriflunomide 14 mg. The relative risk was 1.061 (95% CI: 0.808 to 1.393, p=0.6691), indicating no statistically significant difference.
- Time to Onset of 6-Month Confirmed Disability Worsening: The median time for tolebrutinib 60 mg was 15.38 months, versus 17.97 months for teriflunomide 14 mg. The Hazard Ratio (HR) was 0.85 (95% CI: 0.565 to 1.278, p=0.4888).
- Time to Onset of 3-Month Confirmed Disability Worsening: The median time for tolebrutinib 60 mg was 14.93 months, versus 17.96 months for teriflunomide 14 mg. The Hazard Ratio (HR) was 0.819 (95% CI: 0.582 to 1.151, p=0.2991).
- Mean Number of New and/or Enlarging T2-Hyperintense Lesions Per Year: Tolebrutinib 60 mg had a mean of 5.611 lesions, compared to 5.175 for teriflunomide 14 mg. The relative risk was 1.084 (95% CI: 0.876 to 1.342, p=0.4575).
- Mean Number of New Gadolinium-Enhancing T1-Hyperintense Lesions Per Scan: Tolebrutinib 60 mg showed a mean of 0.530 lesions, compared to 0.285 for teriflunomide 14 mg. The relative risk was 1.86 (95% CI: 1.358 to 2.548, p=0.0001), indicating a statistically significant increase in these lesions for the tolebrutinib group.
- Change From Baseline in Cognitive Function (SDMT): The least squares mean change for tolebrutinib 60 mg was 0.364 (Standard Error: 0.0318), versus 0.329 (Standard Error: 0.0318) for teriflunomide 14 mg. The least square (LS) mean difference was 0.035 (95% CI: -0.053 to 0.124, p=0.432).
What this means
The results from the GEMINI 1 trial indicate that tolebrutinib 60 mg did not demonstrate superiority over teriflunomide 14 mg in reducing the annualized relapse rate in participants with relapsing forms of multiple sclerosis. Similarly, no significant differences were observed for disability progression or T2-hyperintense lesions. Notably, the study found a statistically significant increase in new gadolinium-enhancing T1-hyperintense lesions in the tolebrutinib group compared to the teriflunomide group. These findings suggest that tolebrutinib, at the tested dose, did not provide an efficacy advantage over the comparator in this trial.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04410978, titled "Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)," were posted on 2025-06-18 on clinicaltrials.gov.