Teva Pharmaceutical Industries Ltd. and Active Biotech 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 5th 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 favourable.
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 per cent reduction in the annualized rate of relapses requiring hospitalization and a 27 per cent reduction in those requiring intravenous steroids. Treatment with laquinimod was also associated with a 36 per cent reduction in the risk for three month confirmed EDSS progression (p=0.0122) and a 48 per cent reduction in the risk for six month confirmed EDSS progression (p= 0.0023). Additionally, laquinimod had a positive impact on patient-reported fatigue and cognitive functioning, as assessed by the Modified Fatigue Impact Scale (MFIS) and the short-form (SF)-36 general health survey.
"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."
Laquinimod is an oral, once-daily CNS-active immunomodulator with a novel mechanism of action being developed for the treatment of MS. Laquinimod crosses the blood brain barrier to potentially have a direct effect on resident CNS inflammation and neurodegeneration. The global Phase III clinical development programme evaluating oral laquinimod in MS consists of two pivotal studies, ALLEGRO and BRAVO. In the ALLEGRO study, laquinimod demonstrated a positive impact on disease activity and disability progression, while maintaining a favourable safety and tolerability profile. In addition to the MS clinical studies, laquinimod is currently in Phase II development for Crohn's disease and Lupus, and is being studied in other autoimmune diseases.
Teva Pharmaceutical Industries Ltd. is a leading global pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients.
Active Biotech AB is a biotechnology company with focus on autoimmune/inflammatory diseases and cancer.