Teva Pharmaceuticals has announced that it will no longer pursue the commercial development of laquinimod, a small-molecule aryl hydrocarbon receptor activator, in neurodegenerative diseases. The development and commercialization rights will revert back to Active Biotech, the company that originated the molecule.
Laquinimod had completed three phase III trials in multiple sclerosis with disappointing results. In the BRAVO trial, laquinimod failed to significantly reduce the annualized relapse rate or EDSS progression in RRMS (Vollmer et al. J Neurol 2014;261:773-83). (See also Laquinimod: Few cheers for BRAVO results, NeuroSens, September 21, 2011.) In the ALLEGRO trial, there were modest reductions in ARR and progression, (Comi et al. N Engl J Med 2012;366:1000-9), and a slowing of the rate of brain atrophy (Filippi et al. J Neurol Neurosurg Psychiatry 2014;85:851-8). Following a negative opinion from the European Medicines Agency in 2014, a third phase III trial, CONCERTO, was launched. Laquinimod failed to meet its primary endpoint in that study.
Laquinimod also came up short in phase II studies in primary-progressive MS (ARPEGGIO), Huntington’s disease (LEGATO-HD) and Crohn’s disease (D’Haens et al. Gut 2015;64:1227-35). The drug was also being investigated for nephritis secondary to lupus (Trotter et al. Curr Opin Rheumatol 2016;28:460-7).
Active Biotech, which now owns all of the data produced to date, has stated that it may continue to work on laquinimod as a combination drug.
Laquinimod is the second MS drug to be pulled this year. Daclizumab, a monoclonal antibody, was withdrawn from the market in the spring (see MS therapeutics: 1 withdrawal, 1 setback, NeuroSens, March 5, 2018).