An experimental oral drug to treat relapsing forms of multiple sclorosis (MS) significantly reduced relapses, slowed progression and reduced brain atrophy in a long-term phase III trial being reported at an annual meeting in Hawaii this week.
Laquinimod is an oral, once-daily immunomodulator developed by Teva Pharmaceuticals and Active Biotech.
There are currently two phase III trials investigating the effectiveness and safety of laquinimod as a treatment for MS. The results being presented this week, at the 63rd Annual Meeting of the American Academy of Neurology (AAN) in Honolulu, are for the ALLEGRO trial. The other trial, called BRAVO, is due to report results later this year.
The ALLEGRO trial enrolled 1,106 patients with relapsing-remitting MS in 24 countries and randomly assigned them to receive either a once-daily 0.6 mg oral dose of laquinimod or a placebo. 80% of the drug group and 77% of the placebo group completed the 2-year trial.
The results showed laquinimod patients experienced a statistically significant 23% reduction in annual relapse rate compared to patients who took the placebo.
The laquinimod group also experienced a 36% reduction in disability progression, and a 33% reduction in brain atrophy.
Laquinimod addresses both the acute inflammation activity and the accumulation of irreversible tissue damange of MS, said Principal Investigator, Dr Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the Scientific Institute and University Vita-Salute San Raffaele in Milan, Italy.
“This suggests a substantial future role for laquinimod in the treatment of MS,” he added.
Adverse events in the drug group were comparable to those observed in the placebo group, said Comi.
And, although liver enzyme levels were higher in the drug group, “these elevations were temporary, reversible and did not lead to any signs of liver problems,” he added.
Laquinimod works in several ways to stop the immune system from destroying nerve tissue, the underlying mechanism of MS. For example, animal studies show it shifts the balance of immune response from Th1 (T-Helper 1, cell-mediated) to Th2 (T-Helper 2, antibody-mediated), and it down-regulates certain molecules that are important to inflammation. It also crosses the blood-brain barrier and is thought to play a neuroprotective role by increasing the nerve growth factor BDNF.
In February 2009, the US Food and Drug Administration (FDA) granted laquinimod fast track designation for use in MS.
The drug is also in development for use in treating Crohn’s disease and Lupus, and is being investigated for other immune diseases.
Sources: American Academy of Neurology, Teva Pharmaceutical Industries Ltd, Multiple Sclerosis Resource Centre (UK).
Written by: Catharine Paddock, PhD