Laquinimod (also known as nerventra or ABR-215062) is an investigational therapy being developed by Active Biotech to treat neurodegenerative diseases, including primary progressive multiple sclerosis (PPMS), relapsing-remitting MS (RRMS), and Huntington’s disease.
Laquinimod was previously being jointly developed by Active Biotech and Teva Pharmaceuticals, following an agreement in 2004. As of Sept. 5, 2018, Active Biotech regained sole rights to develop and commercialize laquinimod.
How laquinimod works
Multiple sclerosis (MS) is a condition caused by the immune system mistakenly attacking the myelin sheath, the insulating layer of protein surrounding nerve cells, in the brain and spinal cord. This causes inflammation and damage, impairing the transmission of nerve signals as well as nerve cell death.
Laquinimod is thought to alter the immune response and may protect nerve cells. It is not fully understood how laquinimod works, but it is thought to act as an aryl hydrocarbon receptor (AHR) agonist. AHR is a protein produced by several immune cells. It can be activated by molecules obtained from food or the environment, and is involved in the regulation of the immune response. By binding to and activating AHR, laquinimod may influence the immune response.
Laquinimod is thought to stop damaging immune cells from entering the brain and spinal cord. Furthermore, it may reduce levels of inflammation by promoting anti-inflammatory cytokines (immune proteins) and decrease levels of inflammatory ones. This may prevent or decrease damage to myelin in the brain.
Some studies also suggest that laquinimod increases levels of a protein called brain-derived neuroprotective factor (BDNF), which may help preserve the structure and function of nerve cells.
Laquinimod in clinical trials
Laquinimod has been investigated in several clinical trials for MS. Three Phase 3 studies looked at its effect in RRMS, and a single Phase 2 trial was conducted for PPMS.
ALLEGRO (NCT00509145) was a two-year, randomized, double-blind, placebo-controlled Phase 3 trial in 1,106 RRMS patients. Results, published in the New England Journal of Medicine, showed that daily laquinimod reduced relapse rates by 23% and disability progression by 36% compared with placebo. Magnetic resonance imaging (MRI) data, published in the Journal of Neurology, Neurosurgery, and Psychiatry, suggested that laquinimod slowed the progression of nerve cell death compared with placebo.