GEMINI 1 and 2
Trial question
What is the role of tolebrutinib in patients with relapsing multiple sclerosis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
67.0% female
33.0% male
N = 1873
1873 patients (1252 female, 621 male).
Inclusion criteria: patients, aged 18-55 years, with relapsing multiple sclerosis.
Key exclusion criteria: primary progressive multiple sclerosis or nonrelapsing secondary progressive multiple sclerosis; HIV infection; transplantation; live-attenuated vaccines; progressive multifocal leukoencephalopathy; tuberculosis; hepatitis B or C; persistent chronic or active recurring infection; clinically significant laboratory abnormalities or ECG abnormalities at screening; short life expectancy.
Interventions
N=933 tolebrutinib (at a dose of 60 mg/day plus placebo).
N=940 teriflunomide (at a dose of 14 mg/day plus placebo).
Primary outcome
Annualized relapse rate
0.12
0.12
0.1 relapses
0.1 relapses
0.1 relapses
0.0 relapses
0.0 relapses
Tolebrutinib
Teriflunomide
No significant
difference ↔
No significant difference in annualized relapse rate (0.12 relapses vs. 0.12 relapses; RR 1.03, 95% CI 0.84 to 1.25).
Secondary outcomes
Borderline significant decrease in the rate of confirmed disability worsening for ≥ 6 months (8.3% vs. 11.3%; HR 0.71, 95% CI 0.53 to 0.95).
Borderline significant decrease in the rate of confirmed disability worsening for ≥ 3 months (11.7% vs. 15.3%; HR 0.73, 95% CI 0.57 to 0.94).
No significant difference in confirmed disability improvement for ≥ 6 months (12.6% vs. 10.4%; HR 1.22, 95% CI 0.94 to 1.6).
Safety outcomes
No significant difference in adverse and serious adverse events.
Significant difference in petechiae (4.5% vs. 0.3%).
Conclusion
In patients, aged 18-55 years, with relapsing multiple sclerosis, tolebrutinib was not superior to teriflunomide with respect to annualized relapse rate.
Reference
Jiwon Oh, Douglas L Arnold, Bruce A C Cree et al. Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2025 Apr 8. Online ahead of print.
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