Sunday, 23 February 2014

Laquinimod trìal data published 2 Years after the contents released to Investors

Vollmer TL, et al. J Neurol. 2014 A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis.

The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores of 0-5.5 and documented pre-study relapse (≥ 1 in previous year, 2 in previous 2 years, or 1 in previous 1-2 years and ≥ 1 GdE lesion in the previous year) were randomized (1:1:1) to laquinimod 0.6 mg once-daily, matching oral placebo, or IFNβ-1a IM 30 μg once-weekly (rater-blinded design), for 24 months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly reduced with laquinimod [-18 %, risk ratio (RR) = 0.82, 95 % CI 0.66-1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p < 0.001). Confirmed disability worsening was infrequent (10 % laquinimod, 13 % placebo). The change in confirmed disability worsening with laquinimod measured using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability worsening were -26 and -66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions in ARR and disability progression, but significant reductions in brain atrophy vs. placebo. Laquinimod was well-tolerated

This is the phase III data from laquinimod and the disappointing news based on effects on relapse rate is that it is not very good and in fact worse than beta interferon. However as Prof G has already pointed out the interesting thing is that there was a much better effect on progression of disability and begs the question if this is a neuroprotective drug that can be added onto a more effective DMT.

See recent posts
Multiple Sclerosis Research: EMA's CHMP says no to laquinimod....24 Jan 2014
Multiple Sclerosis Research: Why the results of laquinimod are so ... 07 Jan 2014

The ALLEGRO Trial was reported in mid 2012 but ProfG first posted on the results of the BRAVO trial in November 2011 and "The City" got the news in August 2011 so it is clear that Bankers and Shareholders get their information first and the science media gets the scraps a few years later, especially when the news being spun is not good news.
In response to this News of a "Failed-based on Relapse Rate" Relapsing Remitting MS drug "You" made a comment
"..as a patient rather take a relapse once every third year or so, if I can stop the disability progress. That is the main aim for me as a patient – not the relapses itself!"
"BRAVO study with laquinimod was imbalanced at baseline. The active laquinimod arm was in worse shape than the placebo arm, according to relevant MRI active disease markers at baseline"

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