Sanofi Announces Positive Phase III TEMSO Results
Sanofi and their subsidiary Genzyme announced the publication of their pivotal Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) study with investigational once-daily oral medication teriflunomide in The New England Journal of Medicine (NEJM).
The results showed that teriflunomide, at the 14mg dosage, significantly reduced the yearly relapse rate, reduced disability progressions and improved numerous magnetic resonance imaging (MRI) measures of disease activity, including new or worsening brain lesions.
Teriflunomide has a well-characterized safety profile, with a similar proportion of trial participants reporting adverse events compared to placebo.
Dr. Paul O’Connor, Director of the MS Clinic at St Michael’s Hospital, Toronto, Canada and principal investigator in the TEMSO study, commented that “the TEMSO data demonstrate the effect of teriflunomide in terms of reducing relapse rates, disability progression and Magnetic Resonance Imaging (MRI) lesions.” “These results, sustained over two years, provide clinically meaningful data for teriflunomide.”
The two-year TEMSO (Teriflunomide Multiple Sclerosis Oral) clinical trial involved 1,088 people with relapsing forms of MS from 126 centres across 21 countries. TEMSO is the first study from a broad clinical development program that includes more than 4,000 trial participants in 36 countries and is one of the largest and broadest clinical programs of any oral MS agent under development, with five Phase III clinical trials either completed or underway.
Teriflunomide works by blocking the proliferation and functioning of activated T and B lymphocytes, which are thought to be especially damaging in MS, by selectively and reversibly inhibiting a critical mitochondrial enzyme. Slowly dividing or resting lymphocytes are unaffected by teriflunomide, leaving the immune system’s response to infection uncompromised.
“The publication of the teriflunomide results in the New England Journal of Medicine is an exciting milestone as we continue the development of our product,” added Dr. Elias Zerhouni, President, Global Research & Development, Sanofi. “As we continue our commitment to research, innovation and the Multiple Sclerosis community, we look forward to providing therapeutic options for patients across the Multiple Sclerosis spectrum.”
TEMSO findings showed that, compared to placebo, taking teriflunomide once daily:
- Significantly reduced the risk of annual relapses, by 31% for 7mg and 14mg doses.
- Considerably increased the time till the first relapse, and allowed significantly more trial participants to remain free of relapses during the two years of the study: 53.7% (7mg, p=0.01 vs. placebo), 56.5% (14mg, p=0.003 vs. placebo) and 45.6% (placebo).
- The risk of 12-week confirmed disability progression, the key secondary endpoint, was significantly reduced by 30% for the 14mg dose and numerically reduced by 24% for the 7mg dose.
- Improved several standard magnetic resonance imaging (MRI) measures of disease activity as compared to placebo including new or worsening brain lesions with an apparent dose dependent effect in favour of the 14mg dose:
- Lessoned the burden of disease (by 39.4% and 67.4 % for 7mg and 14mg, respectively)
- Reduced gadolinium-enhancing T1 lesions (relative risk reduction of 57% and 80%, p<0.001 for both doses);
- Reduced unique active lesions per scan (relative risk reduction of 48% and 69%, p<0.001 for both doses).
Similar adverse events, serious adverse events, and adverse events leading to treatment discontinuation were observed with teriflunomide compared to placebo. No serious or opportunistic infections and no deaths occurred in trial participants treated with teriflunomide. The proportion of participants who discontinued the study medication because of disease progression was significantly smaller in the group receiving the 14mg of teriflunomide than in the placebo group (p=0.02). Malignancies were reported in three participants in the placebo group and one in the teriflunomide 14mg group.
Teriflunomide adverse events were usually of mild to moderate intensity, managed with existing therapies and rarely led to treatment discontinuation. The most common were diarrhoea, nausea, liver enzyme increases (that were mainly mild and asymptomatic with no dose effect) and mild hair thinning/decreased hair density. In general, diarrhoea, nausea and alopecia, were mild to moderate, transient, and infrequently led to treatment discontinuation.
With nine years of continuous use in a Phase II extension, teriflunomide has the longest clinical experience of any investigational oral MS therapy. Teriflunomide is also being evaluated as an adjunct therapy to interferon-β in the Phase III TERACLES trial.