August 9, 2012 — Laquinimod, a still investigational oral treatment for relapsing-remitting multiple sclerosis (MS), will be evaluated in a third phase 3 trial after a Special Protocol Assessment (SPA) agreement with the US Food and Drug Administration (FDA), Teva Pharmaceutical Industries Ltd and Active Biotech have announced in a statement.
An SPA agreement between the FDA and a drug sponsor confirms that "the clinical trial protocol is adequate to meet current scientific and regulatory requirements for a potential new drug application," the statement adds.
The trial, dubbed CONCERTO, will assess 2 doses of laquinimod — 0.6 and 1.2 mg daily for up to 24 months — in about 1800 patients with relapsing-remitting MS. The primary outcome will be confirmed disability progression on the Expanded Disability Status Scale (EDSS).
Laquinimod, a once-daily immunomodulator, is one of several oral agents under development for MS. In animal models, laquinimod crosses the blood-brain barrier to potentially have a direct effect on resident central nervous system inflammation and neurodegeneration, the statement notes.
Hope for the agent was supported by results of the Assessment of Oral Laquinimod in Preventing Progression in Multiple Sclerosis (ALLEGRO) trial, published in the March 15 issue of New England Journal of Medicine. ALLEGRO results show that treatment with laquinimod reduced annualized relapse rates and delayed disability progression vs placebo.
However, the situation with laquinimod, at one point hoped to be the second oral agent for treatment of relapsing-remitting MS after fingolimod (Gilenya, Novartis), became more complex with subsequent presentation of results from a second pivotal phase 3 trial, BRAVO, which compared laquinimod with interferon beta-1a (Avonex, Biogen Idec).
That trial missed the primary endpoint of reducing annualized relapse rates, although the reduction seen with laquinimod was significant after researchers adjusted for an imbalance in the volume of T2 disease between groups and the number of gadolinium-enhancing lesions on magnetic resonance imaging.
Both trials showed a reduction in disability that was unexpected given the effect seen on relapse rates, raising the possibility that the agent might be affecting disability through some novel mechanism. A reduction in brain atrophy was also noted, which was in line with the effect on disability — another novel finding with this agent.
BRAVO results were presented last fall at the 5th Joint Triennial Congress of the European and American Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS) in Amsterdam, The Netherlands.
"The results achieved in the previous phase 3 trials of laquinimod support the clinical utility of this compound as a unique treatment option for multiple sclerosis," said Dr. Michael Hayden, president of Global R&D and chief scientific officer at Teva Pharmaceutical Industries Ltd, in the company release. "We are encouraged by the FDA's agreement on the trial design and planned analysis, and look forward to further developing laquinimod as a potential treatment option for RRMS [relapsing-remitting multiple sclerosis] patients."
In addition to the MS clinical studies, laquinimod is currently in phase 2 development for Crohn's disease and lupus, the statement notes.
