CONCERTO: Laquinimod for Relapsing-Remitting MS Fails to Meet Primary Endpoint

Deborah Brauser

May 15, 2017

Topline results from the phase 3 CONCERTO trial show that the oral treatment for relapsing-remitting multiple sclerosis (RRMS) did not meet its primary endpoint, according to an announcement from the manufacturers.

The time to confirmed disability progression (CDP) after at least 3 months did not significantly differ between patients receiving 0.6-mg/day capsules of laquinimod (Teva Pharmaceutical Industries and Active Biotech) and those receiving matching placebo.

The secondary endpoint of time to CDP at 6 to 9 months also did not significantly differ from baseline.

On the other hand, the secondary outcomes of change in brain volume from baseline to month 15 and time to first relapse were significantly improved for the treatment group, as were the exploratory outcomes of annualized relapse rate and reduction of gadolinium-enhancing T1 lesions.

"Although we are disappointed by not meeting the primary endpoint, we did see positive results on a number of secondary and exploratory endpoints, which fuels our belief in the potential of laquinimod as a possible treatment for neurodegenerative diseases," Michael Hayden, MD, PhD, president of Global R&D and chief scientific officer at Teva, said in the statement.

"While we have no current plans to further pursue laquinimod in RRMS, we are continuing to study it in two other trials," Dr Hayden added. It will also continue to be evaluated as a potential treatment for primary progressive MS and Huntington's disease.

Selective AhR Activator

Laquinimod is a selective aryl hydrocarbon receptor (AhR) activator "targeting neurodegeneration and inflammation with a novel mechanism of action," notes the manufacturer.

The multinational CONCERTO trial was first designed to assess two oral doses of the AhR activator in about 2200 patients with RRMS. However, the treatment arm at 1.2 mg/day was discontinued in January 2016.

As reported at the time by Medscape Medical News, Teva announced that it was discontinuing development of both the 1.2- and 1.5-mg doses of the investigational drug after eight patients experienced nonfatal cardiovascular events. No events occurred in the groups receiving the 0.6-mg dose or placebo.

In the newly released topline results, looking only at the 0.6-mg dose vs placebo, the hazard ratio for time to CDP after 3 months or longer (as measured by change on the Expanded Disability Status Scale) was 0.937 (P = .71).

As shown in the following table, many of the secondary and exploratory endpoints were more positive.

Table. Secondary, Exploratory Outcomes for Treatment vs Placebo

Outcome

Finding

P Value

Change in brain volume (from baseline to month 15)

40% improvement

<.0001

Time to first relapse

28% risk reduction

.0001

Annualized relapse risk

25% risk reduction

.0001

Number of T1 lesions

(from baseline to month 15)

30% reduction

.004

 

The most commonly reported adverse events reported by the active treatment group were headache (17%), nasopharyngitis (9%), back pain (7%), and arthralgia (5%).

Full findings from CONCERTO are expected to be presented at a future medical conference.

CONCERTO was the third phase 3 trial of laquinimod in MS. Two previous trials, ALLEGRO and BRAVO, showed divergent findings, with ALLEGRO being positive but BRAVO missing the primary endpoint.

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