Laquinimod – new promising treatment of neurodegenerative diseases

Laquinimod is a once-daily oral, investigational, CNS-active immunomodulator with a novel mechanism of action being developed for the treatment of neurodegenerative diseases. Active Biotech has an agreement since 2004 with the Israeli pharmaceutical company Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) for the development and commercialization of laquinimod.

Development of laquinimod in Huntington's disease, a rare neurodegenerative is ongoing. Laquinimod has been granted Orphan Drug Designation for this indication by the FDA. The Phase 2 LEGATO-HD clinical study will evaluate daily doses of laquinimod as a potential treatment for patients with Huntington's disease. The primary endpoint for LEGATO-HD is change from baseline in the Unified Huntington's Disease Rating Scale-Total Motor Scale (UHDRS-TMS) after 12 months of treatment. Results from the study are expected during 2018.

The global clinical development program evaluating laquinimod in RRMS includes two previously completed Phase III studies, ALLEGRO and BRAVO and the Phase III trial, CONCERTO, evaluating laquinimod in 2,199 patients. Initial results from the CONCERTO trial were communicated in May 2017 and the primary endpoint of time to three-month confirmed disability progression (CDP), as measured by the Expanded Disability Status Scale (EDSS), was not met, nor after six and nine months treatment. However, other study results showed that the secondary endpoints were achieved. Change in brain volume – an indicator of disability progression over time – showed a 40-percent reduction compared to baseline, versus placebo at month 15 (p < 0.0001). Time to first relapse was extended (p = 0.0001). Annualized relapse rate showed a 25-percent risk reduction (p=0.0001). The number of gadolinium-enhancing T1 lesions at month 15, demonstrated a 30-percent reduction (p=0.004). The excellent clinical safety profile of laquinimod 0.6 mg daily, which has been previously studied with over 12,000 patient-years of exposure, was confirmed in the CONCERTO trial. Based on the results of CONCERTO, Teva, as previously announced, does not intend to continue the development of laquinimod in RRMS. Complete data will be published in a scientific journal.

In April 2015, the first patient was enrolled in the ARPEGGIO study, a randomized placebo-controlled Phase II trial evaluating laquinimod in PPMS. The primary endpoint of the study is brain atrophy, defined as the percentage of brain volume change as measured by MRI. Results from the study was announced during the fourth quarter of 2017. The primary endpoint of brain atrophy as defined by percent brain volume change (PBVC) from baseline to week 48, was not met after daily oral doses with 0.6 mg laquinimod. The secondary endpoint of time to confirmed disability progression was also not met. There was, however, a reduction in new T2 lesions observed in patients treated with laquinimod 0.6 mg, suggesting an effect on inflammation of CNS even in patients with PPMS. The clinical safety profile of laquinimod 0.6 mg daily in PPMS patients resembled the safety profile demonstrated in relapsing remitting MS patients.