Laquinimod Fails to Meet Primary Clinical Trial Goal of Slowing Progression of RRMS

Laquinimod failed to meet its primary Phase 3 clinical trial objective of slowing the progression of relapsing-remitting multiple sclerosis (RRMS) after three months, according to its developers, Teva Pharmaceutical Industries and Active Biotech.

That has prompted the partners to abandon their quest to use the therapy to treat RRMS. Laquinimod generated encouraging enough results in the trial that the companies will continue to pursue it as a treatment for other neurodegenerative diseases. For example, it reduced the risk of relapse in RRMS patients by 28 percent.

The key disappointment was that the progression of the disease in the trial’s two treated groups was the same as in a group receiving a placebo, the partners said.

Laquinimod, also known as Nerventra or ABR-215062, targets neurological-tissue inflammation and degeneration. It was developed with the idea that it could treat neurodegenerative conditions besides RRMS, including primary progressive multiple sclerosis (PPMS) and Huntington’s disease.

Preclinical trial studies with animal models of multiple sclerosis were encouraging. Laquinimod regulated inflammatory processes and immune responses in the animals, disrupting the progression of the disease.

Laquinimod failed to slow disease progression in RRMS patients enrolled in the Phase 3 CONCERTO trial (NCT01707992), however. Researchers measured progression with the Expanded Disability Status Scale (EDSS).

The trial design called for some of the 2,200 patients to receive 0.6 mg/day of laquinimod, some to  receive 1.2 g/day, and some to receive a placebo. Adverse cardiovascular events led to the higher dose being discontinued in January 2016, however.

The lower dose of laquinimod failed to meet the trial’s primary objective of slowing the progression of the disease, Teva said. It also failed to meet secondary objectives of slowing the progression at six months and nine months.

Nevertheless, laquinimod yielded some encouraging results, the partners said. To start with, it reduced the risk of relapse in RRMS patients by 28 percent.

It also led to a 40 percent, 15-month reduction in patients’ brain volume – a measure of disability progression – compared with a placebo. And it reduced the number of gadolinium-enhancing T1 lesions in the brain – a measure of inflammation – by 30 percent over the 15 months.

“We have learned a great deal from the CONCERTO trial, and we will continue our analysis of the data,” Michael Hayden, the chief scientific officer at Teva, said in a press release.

“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,” he said. “While we have no current plans to further pursue laquinimod in RRMS, we are continuing to study it in two other trials.”

Teva is evaluating the potential of laquinimod in PPMS and Huntington’s with the clinical trials (NCT02284568 and NCT02215616).

CONCERTO trial results will be published in a scientific journal and presented at a medical meeting, the partners said.