Oral laquinimod shows promise against multiple sclerosis

Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) today announced the presentation of Phase III clinical and pre-clinical data, which collectively demonstrate that once-daily oral laquinimod modulates the pathological processes of multiple sclerosis to impact disease activity, disability progression and brain volume loss. The data will be featured in more than 20 scientific posters and presentations this week at the 5^th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) in Amsterdam, The Netherlands.

Findings from the second Phase III study, BRAVO, being highlighted as late-breaking research, showed that at 24-months, the primary endpoint of reduction in annualized relapse rates (ARR) did not reach statistical significance (0 = 0.075); however, after applying a pre-specified sensitivity analysis to correct for meaningful imbalances in baseline characteristics (MRI) between treatment groups, laquinimod significantly reduced ARR (21.3%, p = 0.026). Laquinimod also demonstrated a significant reduction in the risk of disability progression as measured by the Expanded Disability Status Scale (EDSS) (33.5%, p = 0.044) and in MRI-measured brain volume loss (27.5%, p =< 0.0001). The safety and tolerability profile of laquinimod was favorable.

New exploratory analyses from ALLEGRO, the first Phase III study in the laquinimod clinical development program, demonstrated that laquinimod had an effect on the rate of severe relapses, showing a 38 percent reduction in the annualized rate of relapses requiring hospitalization and a 27 percent reduction in those requiring intravenous steroids. Treatment with laquinimod was also associated with a 36 percent reduction in the risk for three month confirmed EDSS progression.

"The life-long, debilitating nature of multiple sclerosis and well-recognized clinical variability, underscore the need for therapies that can slow disease progression and improve patient treatment experience," said Professor Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy. "Both the ALLEGRO and BRAVO studies provide consistent evidence of a clear impact of laquinimod on progression of disability and brain atrophy, measures of the neurodegenerative process of MS. These effects on disease burden, together with the effects on relapse management, the convenience of oral administration and the excellent safety and tolerability profile represent a unique approach to the treatment of MS."

"Several supportive pre-clinical studies being presented further elucidate the potential novel mechanisms of action of laquinimod, which target both neurodegeneration occurring directly in the CNS and peripheral inflammation," said Wolfgang Brück, M.D., Director of Neuropathology at Georg-August-University in Goettingen, Germany. "The cuprizone and EAE mouse model studies showed that laquinimod reduced demyelination, axonal damage and resulted in dose-dependent decreases in pro-inflammatory cytokines, further demonstrating that the compound acts directly on resident CNS cells to decrease neurodegeneration and brain volume loss."

"The data presented at ECTRIMS contribute to the growing body of scientific evidence supporting the novel clinical profile of laquinimod," said Jon Congleton, Teva's Vice President, Global Strategic Marketing. "We are excited by the prospect of laquinimod providing a treatment option that addresses important attributes of RRMS therapy, namely reduction of disability progression and irreversible tissue loss, without compromising convenience, safety or tolerability."