Arimoclomol (Orph-001) is a therapy that Orphazyme and the University of Miami are developing to treat amyotrophic lateral sclerosis (ALS).

How arimoclomol works

ALS is a neurodegenerative disease characterized by the death of motor neurons, or nerve cells that control muscle movement, leading to paralysis, a hallmark of the disease.

The exact cause of ALS is not known but it is known that some forms are inherited, resulting from a mutation in the superoxide dismutase 1 (SOD1) gene. This gene encodes for the SOD1 protein and the mutation changes the way the protein functions.

It is not clear how altered SOD1 protein causes the death of motor neurons, but researchers think it could be through one or a combination of factors. It may lead to an increase in levels of harmful substances that SOD1 normally breaks down, it may cause an increase in the production of other types of toxic substances, or it may form clumps that accumulate inside cells and cause their death.

Arimoclomol triggers an increase in the production of heat shock proteins, or HSPs, which are involved in the body’s response to stress. HSPs bind to faulty proteins. They also regulate the programmed cell death pathway, a mechanism by which the body gets rid of damaged cells.

In ALS, one of the HSPs — HSP70 — can bind to faulty SOD1 protein and remove it. By increasing the production of HSP70, arimoclomol may reduce the rate of motor neuron death and slow the progression of ALS.

Arimoclomol in trials

A preclinical trial study of arimoclomol’s ability to treat mice with ALS appeared in the journal Nature Medicine. The treated mice were able to move much better than untreated mice when they became older, and lived 22 percent longer. The findings suggested that arimoclomol could be an effective treatment for ALS.

A Phase 2/3 clinical trial (NCT00706147) showed that arimoclomol was safe, and that patients tolerated it well. Orphazyme enrolled 36 patients with SOD1-related ALS for the trial. The participants received either arimoclomol or a placebo three times a day for up to 12 months.

The results of the study were published in the scientific journal Neurology and showed that patients who took arimoclomol potentially lived longer than those who received a placebo. In addition, those receiving arimoclomol declined more slowly than those receiving placebo in several functional measure tests. These included the revised ALS functional rating scale (ALSFRS-R), percent predicted forced expiratory volume in six seconds (FEV6, a measure of lung function), and the combined assessment of function and survival (CAFS).

Following these positive results, Orphazyme is now enrolling an estimated 231 participants for a Phase 3, randomized, double-blind, placebo-controlled trial (NCT03491462) at sites across the U.S., Canada, and Europe. Participants will receive either arimoclomol or a placebo for up to 76 weeks. The study will monitor CAFS periodically to determine whether there is a difference between the two groups. Other metrics that will be measured are time to permanent assisted ventilation (PAV)/tracheostomy/death, changes in ALSFRS-R, and changes in slow vital capacity over time, another measure of lung function.

Orphazyme expects interim results from this study in the second half of 2020, with final results being available in the first half of 2021.

Additional information

In addition to ALS, Orphazyme is also conducting trials of arimoclomol as a treatment for sporadic inclusion body myositisNiemann-Pick type C, and Gaucher disease.


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