Active Biotech, based in Lund, Sweden, announced that its laquinimod failed to meet its primary endpoint in its Phase II clinical trial for Huntington’s disease.
Active Biotech, based in Lund, Sweden, announced that its laquinimod failed to meet its primary endpoint in its Phase II clinical trial for Huntington’s disease.
The drug is licensed to Teva Pharmaceutical Industries in 2004. The primary endpoint in the Phase II LEGATO-HD trial was change from baseline after 12 months of treatment measured by the Unified Huntington’s Disease Rating Score – Total Motor Score (UHDRS-TMS). Although it didn’t mean the primary endpoint, the drug met the study’s secondary endpoint, a decrease of brain atrophy measured by caudate volume. The safety profile was consistent with what was observed in multiple sclerosis trials.
The clinical trial was sponsored by Teva Pharmaceutical in collaboration with the Huntington Study Group and the European Huntington’s Disease Network. The LEGATO-HD is a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group Phase II trial. It is evaluating three doses, 0.5 mg, 1.0mg, and 1.5mg compared to placebo. The study looked at 352 patients with a mean age of 43.9 years, split almost evenly between men and women. Of the total group, 287 completed the study while 65 ended early, including 30 patients who stopped when the 1.5mg dose was terminated.
Huntington’s disease in an inherited disease that results in the progressive degeneration of nerve cells in the brain. Patients typically develop signs and symptoms in their 30s or 40s, although it can show up earlier or later. When it emerges before the age of 20, it is called juvenile Huntington’s disease, and has faster progression and a generally different group of symptoms. Symptoms are usually movement, cognitive and psychiatric disorders, such as involuntary jerking or writhing movements, rigidity or muscle contracture, slow or abnormal eye movements, impaired gait, posture and balance, difficulty swallowing or talking.
Full data is still being analyzed and Teva expects to present the results at future medical conferences and publish data in peer-reviewed journals.
In its first-quarter financial report in March, Active supplied a number of updates on its technical programs, including laquinimod, which was also being investigated for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS). It had completed two earlier Phase III trials in RRMS, ALLEGRO and BRAVO, and the Phase III trial, CONCERTO, which evaluated the drug in 2,199 patients. In the CONCERTO trial, in May 2017, the drug didn’t meet its primary endpoint of time to three-month confirmed disability progression (CDP), as measured by the Expanded Disability Status Scale (EDSS). It didn’t meet it at the six or none months period, either. Again, some secondary endpoints were achieved. Change in brain volume, which is an indicator of disability progression over time, showed a 40 percent decrease compared to baseline versus placebo at 15 months.
In addition, the time to the first relapse was extended and an annualized relapse rate had a 25 percent risk reduction. The number of gadolinium-enhancing T1 lesions at 15 months showed a 30 percent decrease. The drug also had a good safety profile for the 0.6mg daily dose. At that time, based on CONCERTO results, Teva didn’t plan to continue developing the drug in RRMS.
In the ARPEGGIO trial, the primary endpoint of brain atrophy as defined as the percentage of brain volume change was measured by MRI was not met.
