Orphazyme Doses First ALS Patient in Phase 3 Trial of Arimoclomol

The first patient has been dosed in a Phase 3 clinical trial (NCT03491462) evaluating the effectiveness of Orphazyme’s investigational therapy arimoclomol in the treatment of amyotrophic lateral sclerosis (ALS).

One of the disease mechanisms known to be involved in the development of ALS is protein misfolding and aggregation in nerve cells that control movement (motor neurons). Researchers have looked for ways to target this abnormality as a therapeutic strategy.

Arimoclomol, currently in clinical trials as a potential treatment of ALS and other diseases, increases the production of a group of proteins called heat-shock proteins (HSPs).

HSPs work to counteract the protein aggregation, in part by improving the function of lysosomes — cellular organelles that act as the waste disposal system of cells and work to remove undesirable materials.

Arimoclomol, which has been investigated in Phase 1 and Phase 2 clinical trials, is administered orally. Importantly, it is able to cross the blood-brain barrier, which is crucial for treating neurological diseases. Previous clinical trials have indicated that arimoclomol has a favorable safety and tolerability profile.

“This is a truly devastating disease and we will work to expeditiously advance the Phase III trial with the prospect of making a new therapeutic option available to the patients in the shortest possible timeframe,” Thomas Blaettler, Orphazyme’s chief medical officer, said in a press release.

The randomized, placebo-controlled study plans to enroll 231 patients across 30 centers in North America and Europe. They will be randomized in a 2:1 ratio to receive either capsules of arimoclomol or placebo for up to 76 weeks.

Its primary endpoint is the effectiveness of long-term treatment with arimoclomol over the placebo, as evaluated by a combined assessment of function and survival.

Secondary objectives include changes in survival, ALSFRS-R (a functional rating scale), and slow vital capacity (SVC), a measure of lung function.

After the study is completed, patients will have an option to participate in an open-label extension trial. More information about the Phase 3  study, including contacts for enrollment, is available here.

Michael Benatar, an MD and PhD, the principal investigator of a previous Phase 2 trial of arimoclomol in ALS patients with the SOD1 gene mutation (one of the most common mutations linked to ALS), said, “I am delighted to see arimoclomol advance into Phase III testing and that the eligible population has been broadened to include all patients with ALS.”

“Based on the mechanism of action of the drug and our understanding of the underlying biology of ALS, there is good reason to believe that all patients with ALS might benefit from this therapeutic approach,” Benatar added.

ALS, a progressive neurological disorder, is characterized by an impairment of voluntary muscle action, caused by degeneration of nerve cells in the brain and the spinal cord.

Currently, there is no effective long-term therapy for treating this neurodegenerative disease. Nearly 50,000 people are estimated to be affected by ALS in Europe and the United States.