Multiple sclerosis drug in development: laquinimod
A new oral multiple sclerosis drug in development, Nerventra (laquinimod), appears to have modest effects on relapses but there is a possibility of long-term benefits, according to the newly-published results of the BRAVO trial (Vollmer and colleagues. J Neurol 2014; epublished February 18, 2014).
BRAVO is one of two large phase III studies examining the effect of Nerventra in MS. Over one thousand people were given either oral Nerventra 0.6 mg a day, Avonex by intramuscular injection once a week, or a placebo. At the end of two years, the annualized relapse rate (ARR; the number of relapses averaged over two years) was reduced 18% with laquinimod, however, this was not significantly different from the placebo. The study didn’t directly compare Nerventra and Avonex, but Avonex appeared to be the more effective drug, with an ARR reduction of 26%.
The proportion of people experiencing disability worsening was lower with Nerventra compared to placebo (10% vs. 13%), but was not statistically significant. The one bright spot was a significant reduction in the rate of brain atrophy (global shrinkage of the brain) with Nerventra compared to placebo. Brain atrophy may be the best predictor of future disability in MS (Radu and colleagues. Swiss Med Wkly 2013;143:13887), but it remains to be seen if Nerventra’s effect on this measure will translate to a better outcome for people with MS.
The modest effect of Nerventra on traditional measures of MS drugs (relapses, MRI, progression) was also seen in ALLEGRO, the other phase III trial. (ALLEGRO is available as a free download from the MSology Library.) Again, while Nerventra didn’t appear to have a potent anti-inflammatory effect in the brain (as measured by relapses and EDSS score), there was a 36% reduction in disability progression (Comi and colleagues. N Engl J Med 2012;366:1000-9).
Thus far, health regulators have not been overly impressed with Nerventra. The U.S. Food and Drug Administration fast-tracked the drug in 2009 but has still not approved it. The European Medicines Agency formally rejected laquinimod in January 2014 (www.ema.europa.eu…pdf.). The EMA expressed a concern that prolonged exposure to the drug was associated with a risk of cancer in animals.
Nerventra (formally known as ABR 215062) was developed by a Swedish company, Active Biotech, and has been licensed to Teva Pharmaceuticals, which makes Copaxone. Both companies have announced that they remain keen on the drug despite its recent setbacks (http://ir.tevapharm.com…). A third phase III trial called CONCERTO will investigate whether a higher dose is more effective.
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