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 relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and Huntington's disease (HD). The global clinical development program evaluating laquinimod in MS includes two previously completed Phase 3 studies, ALLEGRO and BRAVO and the Phase 3 trial, CONCERTO, evaluating laquinimod in 2,199 patients.  Initial results from the CONCERTO trial was released 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 meet. Other data show that on the secondary endpoint which measured change in brain volume - an indicator of disability progression over time - compared to baseline was positive (40% improvement over placebo at month 15, p < 0.0001). Furthermore, encouraging results were seen on the secondary endpoint of time to first relapse (risk reduced by 28%; p = 0.0001) and the exploratory endpoint of annualized relapse rate (risk reduced by 25%; p=0.0001). As with the primary endpoint, secondary endpoints measuring time to 6 and 9 months confirmed CDP did not reach significance. On the exploratory endpoint of reduction of the number of gadolinium-enhancing T1 lesions at month 15, laquinimod demonstrated a 30% reduction (p=0.004). The clinical safety profile of laquinimod 0.6 mg daily, which had been previously studied with over 12,000 patient-years of exposure, was confirmed in CONCERTO. Further evaluation of the CONCERTO trial is ongoing and complete data will be published in a scientific journal and presented at a future medical meeting.

Extension studies with more than 1000 patients from the clinical Phase 2 and Phase 3 studies, ALLEGRO and BRAVO, are under way.

In April 2015 the first patient was enrolled in the ARPEGGIO study, a randomized placebo-controlled Phase 2 trial evaluating laquinimod in primary progressive MS, (PPMS). The primary endpoint of the study is brain atrophy, defined as the percentage brain volume change as measured by MRI. Results from the study are expected during H2 2017.

Development of laquinimod in Huntington's disease, a rare neurodegenerative disease has also been initiated. Laquinimod has been granted Orphan Drug Designation for this indication by the FDA. The Phase 2 LEGATO-HD clinical study is ongoing and 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.

Active Biotech has an agreement with the Israeli pharmaceutical company Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) for the development and commercialization of laquinimod".

Multiple sclerosis

Read about the disease in Swedish here>>

Multiple sclerosis (MS) is a chronic, progressive disease affecting the central nervous system. The disease affects the central nervous system (the brain and spinal cord). The symptoms are caused by the body's own immune system attacking and damaging the myelin sheaths surrounding nerve fibers. This causes inflammation within the central nervous system causing the patient to suffer relapses and disease progression. The etiology of the disease is unknown, but is assumed to depend, like other autoimmune diseases, on both genetic and environmental factors.

There are various forms of MS, the most common is relapsing remitting MS ("RRMS"). It is characterized by unexpected recurring relapses that can last from a few days to a few weeks and are followed by complete or partial remission. In approximately 80 percent of all patients, the disease begins as RRMS but most develop after some ten or so years into secondary progressive MS ("SPMS"), which is characterized by a gradually increasing degree of disability, without the recovery periods.

MS primarily affects young and middle-aged people. The disease often first appears when the patient is between 20 and 50 years old, and the number of women affected is twice as high as the number of men. A total of about two million people throughout the world suffer from MS. The disease is more common in the northern hemisphere. The Nordic region, the British Isles and North America are regarded as high-risk areas.

There are currently several types of disease modifying drugs available for treatment of MS. Since many years the injectable beta-interferon products and glatiramer acetate have been available and are still widely used. More recently, two injectable antibody products, natalizumab and alemtuzumab have been approved for treatment of MS. There are also three oral products that have been approved during the last few years, fingolimod, teriflunomide and dimethyl fumarate. The drugs reduce the number of relapses and are therefore all approved for treatment of MS patients with relapses.