Sanofi and its subsidiary Genzyme announced positive top-line results from the TOPIC trial for Aubagio (teriflunomide). The trial was designed to assess whether early initiation of Aubagio (teriflunomide) in patients who experienced their first neurological symptoms consistent with Clinically Isolated Syndrome (CIS) can prevent or delay conversion to clinically definite multiple sclerosis (CDMS).
Clinically isolated syndrome (CIS) is defined as a first clinical attack with features suggestive of MS. It typically occurs in young adults and is often a prelude to CDMS.
In the TOPIC trial, patients receiving Aubagio 14 mg and 7 mg were significantly less likely to develop CDMS, defined as occurrence of a second clinical attack, the primary endpoint, as compared to placebo. Additional results, including key secondary and tertiary objectives, will be presented at a forthcoming scientific meeting.
Primary results were: In patients who received Aubagio 14 mg, a 43 per cent reduction in risk of conversion to CDMS was observed over the two-year study period, compared to placebo (p=0.0087); In patients who received Aubagio 7 mg, a 37 per cent reduction in risk of conversion to CDMS was observed over the two-year study period, compared to placebo (p=0.0271).
“Clinically Isolated Syndrome (CIS) is often a prelude to clinically definite multiple sclerosis, and early treatment has proved beneficial,” said Dr. Aaron E Miller, medical director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center. “These findings are important as there is an unmet need for an efficacious oral option for patients at this stage of disease.”
The average duration of Aubagio exposure in TOPIC was approximately 16 months. Adverse events observed in the trial were consistent with previous clinical trials with Aubagio in MS. The most common types of adverse events reported more frequently in the Aubagio arms were ALT (Alanine transaminase) elevations, nasopharyngitis, headache, hair thinning, diarrhea and paresthesia. There were no deaths reported in either teriflunomide group over the course of the study. There was one death due to suicide in the placebo arm. The rate of treatment discontinuation due to adverse events was similar across treatment arms (9.1 per cent in placebo arm, compared to 12.1 per cent in 7 mg teriflunomide arm and 8.3 per cent in 14 mg teriflunomide arm).
“Aubagio is the only oral marketed MS therapy to successfully be studied in CIS and we are very pleased by these topline results which further reinforce the consistent efficacy and potential for treating a broad spectrum of MS patients,” said Genzyme president and CEO, David Meeker, MD. “We remain committed to addressing unmet needs in MS through new areas of research and delivery of differentiated therapies for this devastating disease.”
The trial compared treatment with either 14 mg or 7 mg once-daily, oral Aubagio against placebo.
This double-blind, multi-center trial enrolled 618 patients who had experienced a first acute or subacute, well-defined neurological event consistent with demyelination, as well as onset of MS symptoms within 90 days of randomization, and MRI scan showing two or more T2 lesions characteristic of MS.
Aubagio is approved in the US, Australia and Argentina for the treatment of relapsing forms of MS. Marketing applications for Aubagio are also under review by regulatory authorities globally.
The ongoing Aubagio clinical development programme, involving more than 5,000 patients in 36 countries, is amongst the largest of any MS therapy. Some patients in extension trials have been treated for up to 10 years.
Aubagio is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for Aubagio is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system (CNS).