Health Canada approves third oral therapy in Canada for relapsing-remitting MS
Health Canada has approved oral therapy AUBAGIO™ (teriflunomide) for the treatment of people with relapsing remitting multiple sclerosis (RRMS) to reduce the frequency of relapses and to delay the accumulation of physical disability.
The Health Canada approval was based on data from two pivotal phase III clinical trials referred to as TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis). Both trials were similar in study design and sample population:
- Multicentre, multinational, randomized phase III trial
- Double-blinded (neither the participants nor the researchers know which participants are receiving teriflunomide and which are receiving a placebo treatment; this is done to avoid bias)
- Approximately 1,000 people were tested, aged 18-55 and with relapsing-remitting MS (RRMS)
- Doses administered were 7 mg and 14 mg
- Researchers measured annualized relapse rate and disability progression
TEMSO involved additional MRI tests to observe changes in the number and size of lesions in the brain following treatment with teriflunomide.
In the TEMSO trial, both doses of teriflunomide significantly reduced the annualized relapse rate (31%) compared with placebo treatment in people with RRMS. Treatment with teriflunomide also showed a beneficial effect on the progression of disability, which was significantly reduced over 2 years in people treated with teriflunomide 14 mg versus placebo.
Data from MRI showed a significant reduction in lesion volume in individuals treated with teriflunomide 7 mg (39% reduction) and teriflunomide 14 mg (67% reduction) as well as a reduction in the number of lesions compared with placebo.
In the TOWER trial, teriflunomide 7 mg reduced the annualized relapse rate by 22%, and teriflunomide 14 mg reduced the annualized relapse rate by 36%. As with the earlier TEMSO study, teriflunomide 14 mg demonstrated a significant reduction in the time to disability versus placebo in people with RRMS.
TEMSO 5-year extension
An extension study was undertaken to evaluate the long-term effects of teriflunomide. Data from the study showed a sustained reduction in annualized relapse rate 5 years after initiation of treatment compared with placebo.
TENERE (TErifluNomidE and REbif®)
A third study was conducted to compare the effectiveness and safety of teriflunomide with interferon beta-1a in people with RRMS. Researchers observed the time to a confirmed relapse or treatment discontinuation, defined as ‘time to failure’. Also measured were annualized relapse rate, fatigue, treatment satisfaction, and safety and tolerability.
TOPIC (Teriflunomide versus Placebo in Patients with First Clinical Symptom of MS):
This is the newest trial with teriflunomide. It is a 2-year, multicentre, double-blinded phase III study in people with early clinical symptoms of MS (referred to as clinically isolate syndrome or CIS). The primary objective is to demonstrate that early intervention with teriflunomide in people presenting with their first neurological episode consistent with MS prevents or delays conversion to clinically definite MS.
Early results of the trial were presented by Dr. Aaron Miller from the USA in October at the European Committee for Treatment and Research in MS (ECTRIMS) Congress in Copenhagen Denmark. Data showed that early treatment with teriflunomide can lower the likelihood that someone with CIS will convert to clinically definitive MS and, in people who are already relapsing, decrease the risk of new relapses. In addition, MRI revealed a five per cent increase in lesion volume among people treated with teriflunomide 14 mg compared to a 28% increase among people treated with placebo.
Summary of Research:
Overall both TEMSO and TOWER demonstrated a significant effect of teriflunomide on relapse activity and disability progression in people with RRMS. Both trials were undertaken to demonstrate consistency in treatment effects, with additional imaging tests conducted in TEMSO to evaluate subclinical effects. The MRI data revealed that both doses of teriflunomide significantly decreased lesion volume compared with placebo, with a dose-dependent response observed (the greater the dose, the greater the reduction in lesion volume). Both doses of teriflunomide showed no serious adverse events and a similar tolerability and safety profile. Additional studies with teriflunomide, such as TENERE and TOPIC, have provided and will continue to provide more information on the full clinical effects and long-term safety of the drug.
Mechanism of Action:
The exact biological mechanism of teriflunomide is not fully understood, but likely to involve immunomodulation. That means it has the ability to impact the activity of the immune system. More specifically, teriflunomide can reduce the number of highly dividing white blood cells that have the capacity to enter the nervous system from the bloodstream and cause harm to myelin. Teriflunomide does not affect those white blood cells that are still required to protect the body against infection.
AUBAGIO™ is a once-daily, oral treatment indicated as a monotherapy for the treatment of people with relapsing-remitting MS (RRMS). The recommended dose of AUBAGIO™ is 14 mg orally once daily, which can be taken with or without food. Monitoring is recommended prior to initiating and during treatment. The most common adverse events associated with AUBAGIO™ in people with MS included diarrhea, increased liver enzymes (ALT levels), alopecia (hair loss), headache and nausea. The safety and efficacy of AUBAGIO™ in children with MS under 18 and in people over 65 have not yet been evaluated. As well, AUBAGIO™ is contraindicated in women who are pregnant or women of child bearing potential not using reliable protection.
Selecting an MS therapy should be done by people with MS in collaboration with their MS doctors, taking into account a variety of factors, including the effectiveness of any therapy they are currently using, and weighing potential risks and benefits, costs and lifestyle factors. AUBAGIO™ is not yet available in Canadian pharmacies however the MS Society of Canada will share this information as it becomes available.
Please visit the MS Society information page on AUBAGIO™ for more information.