Research: Teriflunomide 8 years on

R

C Confavreux et al. Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years [Mult scler J. Feb Epub ahead of print]

Background: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study.

Methods: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010.

Results: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05–8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic Linkalanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases greater thanv ;3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients.

Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters.

Conclusion: Teriflunomide had a favourable safety profile for up to 8.5 years.

Although Teriflunomide may appear to be relatively safe, the issue of level of efficacy may determine how well this orally-active compound is recieved. So whilst teriflunomide is effective it is not that effective. In the initial phase II trial , from which the followi-up is derived there was no significant inhibition of the relapse rate but did affect some other outcomes. However this drug has been studied in a phase III trial involving over 1000 people and oral Teriflunomide (Trade name Aubagio-Who comes up with these names?) inhibits the relapse rate only by about 30% and is no better than beta interferon when compared in a head to head fashion in recent studies involving over 300 hundered MSers. Whilst it has the advantage of being an oral drug verses interferons, it will be interesting to see how it will do compared to Gilenya and BG-12 that are much more active. However, this will depend on safety profiles and we have yet to see if the recent deaths of people taking Gilenya are going to impact on the use of the drug.

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MouseDoctor

5 comments

  • $100m in development going down the drain…. but not to worry, "successful" drugs are prices so steeply to cover the lagers and failures.

  • Just curious…how long was Gilenya's safety profile before it was approved last year? I was so looking forward to ditching Copaxone and getting on BG-12 as soon as it's approved, but the recent Gilenya-associated deaths have made me gun-shy.

    Sigh 🙁

  • Dear Maria

    How long was Gilenya's safety profile

    I.m not sure what you are asking can you re phase the question.

    Bes wishes

  • Re: "Just curious…how long was Gilenya's safety profile before it was approved last year?"

    The subjects in the phase 2 extension was at ~7-years of exposure and the in the phase 3 extension ~4 years. The problem with rare events they often only emerge after the drug has been launched. On the other side of the coin the sudden deaths may turn-out to be due to MS rather than due to fingolimod. We need to wait for the EMA's review of the cases to see what their call is on this issue. So in the interim it is better to err on the side of being safe.

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