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|October 04, 2013 9:45 a.m.|
|New Data Presented at 29th ECTRIMS Congress Reinforce the Clinical Profile of Investigational Laquinimod on Disease Progression and Inflammation in Relapsing-Remitting Multiple Sclerosis|
Pooled Data Analysis of Phase III ALLEGRO and BRAVO Studies Add to our Understanding of Investigational Laquinimod for Relapsing-Remitting Multiple Sclerosis (RRMS)
"Continued analysis of the ALLEGRO and BRAVO Phase III studies
demonstrates that the trend of efficacy results was maintained in the
analysis of data pooled from the two studies, and is consistent with the
proposed mechanism of action for laquinimod," said Dr.
Results from a post-hoc subgroup analysis of pooled data from the Phase III double-blind ALLEGRO and BRAVO studies showed there were some patients who experienced disease progression without experiencing a relapse during the studies. Regardless of treatment arm and despite relapse status, 12 percent of patients studied experienced disability progression after two years; of those patients who progressed, approximately one-third did not experience a relapse. Results specific to treatment with laquinimod showed that both relapsing and relapse-free patients treated with laquinimod experienced less disease progression than those treated with placebo. Specifically, 19 percent of relapsing patients on laquinimod progressed compared to 22 percent on placebo and 4.8 percent of relapse-free patients on laquinimod progressed compared to 7.6 percent on placebo. Overall, laquinimod reduced disability progression by 26.7 percent in relapsing patients (P=0.058) and 38.9 percent in relapse-free patients (P=0.036) compared to placebo.
Both the ALLEGRO and BRAVO studies found that laquinimod demonstrated a tolerable clinical profile compared to placebo. The overall frequencies of adverse events, including incidence of infections, were comparable to those observed in the placebo group. The most commonly reported adverse events were headaches, nasopharyngitis and back pain. The incidence of liver enzyme elevation was higher in laquinimod treated patients; however, these elevations were transient, asymptomatic and reversible. No deaths were reported in laquinimod-treated patients.
“We have made significant progress in understanding the pathology of
multiple sclerosis however it remains a complex and often unpredictable
disease,” said Professor
Results of this study will be presented at the
ABOUT THE ALLEGRO STUDY
ALLEGRO was a two-year, multi-national, multi-center randomized, double blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of laquinimod in MS patients. The study was conducted at 139 sites in 24 countries and enrolled 1,106 MS patients. Patients were randomized to receive a once-daily oral dose of 0.6 mg laquinimod or matching placebo. The primary outcome measure was the number of confirmed relapses; secondary measures included confirmed disability progression and changes in MRI active lesions.
In the ALLEGRO study, laquinimod showed a statistically significant 23 percent reduction in annualized relapse rate (p=0.0024), the primary endpoint, along with a significant 36 percent reduction in the risk of confirmed disability progression, as measured by Expanded Disability Status Scale (EDSS) (p=0.0122). Treatment with laquinimod was also associated with a significant reduction in brain tissue loss, as measured by a 33 percent reduction in progression of brain atrophy (p<0.0001).
Eighty percent of laquinimod and 77 percent of placebo patients completed the two-year study. Patients who completed the ALLEGRO study were offered to join an open-label extension phase, in which they are being treated with laquinimod 0.6 mg daily.
ABOUT THE BRAVO STUDY
BRAVO was a two-year, multi-national, multi-center, randomized,
double-blind, parallel-group, placebo-controlled study designed to
compare the safety, efficacy and tolerability of a once-daily oral dose
of 0.6 mg laquinimod over placebo and to provide a descriptive
comparison of the risk-benefit profiles of laquinimod and interferon
beta-1a. The primary outcome measure was to assess the efficacy of 0.6
mg daily dose of laquinimod as measured by the relapse rate. Secondary
outcome measures included impact on the accumulation of disability and
brain atrophy. The BRAVO study completed enrollment in
Results showed that the BRAVO study did not achieve its primary endpoint of reducing the annualized relapse rate (p=0.075).
Laquinimod is an oral, investigational, CNS-active immunomodulator with a novel mechanism of action being developed for the treatment of relapsing-remitting MS (RRMS). The global Phase III clinical development program evaluating oral laquinimod in MS includes two pivotal studies, ALLEGRO and BRAVO. A third Phase III laquinimod trial, CONCERTO, is evaluating two doses of the investigational product (0.6mg and 1.2mg) in approximately 1,800 patients for up to 24 months. The primary outcome measure will be time to confirmed disability progression as measured by the EDSS.
In addition to the MS clinical studies, laquinimod is currently in Phase II of development for Crohn's disease and lupus nephritis. Further studies are planned to determine the effectiveness of laquinimod in treating patients with Huntington’s disease and Alzheimer’s disease.
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