Enrollment Complete for ORARIALS-01 Trial of Arimoclomol in ALS Patients

Patient enrollment is now complete, ahead of schedule, for the Phase 3 ORARIALS-01 clinical trial assessing the effectiveness of Orphazyme’s investigational therapy arimoclomol in the treatment of amyotrophic lateral sclerosis (ALS).

“The completion of enrollment for Orphazyme’s pivotal ALS trial is another great milestone for our clinical development program. We are confident that the trial design and 18-month trial duration will maximize our ability to demonstrate efficacy,” Thomas Blaettler, MD, chief medical officer of Orphazyme, said in a press release.

Accumulation of abnormal (misfolded) proteins in nerve cells that control movement (motor neurons) is one of the mechanisms promoting ALS. Researchers have looked for ways to target this abnormality as a therapeutic strategy.

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

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

Most importantly, arimoclomol is able to cross the blood-brain barrier, a highly selective membrane that shields the central nervous system with  cerebrospinal fluid from the general blood circulation.

The ORARIALS-01 trial (NCT03491462), underway at 29 clinical sites in the U.S., Canada and Europe, has recruited 231 patients.

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A total of 213 patients will be divided randomly into two groups that will receive either arimoclomol capsules or placebo for up to 76 weeks. A group of 18 participants undergoing treatment with Mitsubishi Tanabe’s Radicava (edaravone) also will join the trial in the U.S.

The study’s primary goal is the effectiveness of long-term treatment with arimoclomol over the placebo, as evaluated by a combined assessment of function and survival (CAFS).

Secondary objectives include changes in the ALSFRS-R (a functional rating scale), slow vital capacity (SVC), a measure of lung function, and the time until patients require permanent assisted ventilation.

After the study is completed, patients will have an option to participate in an open-label extension trial (NCT03836716), which will continue to explore the therapy’s long-term effectiveness and safety.

The support of the ALS community worldwide, including patients and their families, was key for the successful completion of enrollment.

“It is thanks to the tireless efforts of investigators and coordinators at participating centers across the world that we have been able to reach this important milestone, bringing us one step closer to definitively learning whether arimoclomol is beneficial for patients living with ALS,” said Michael Benatar, MD, PhD, University of Miami, and the study’s lead investigator.

“We are grateful to the hundreds of people living with ALS around the world for participating in this trial. We urgently need new treatments for ALS and we look forward to the results,” Calaneet Balas, president and CEO of the ALS Association and chairwoman of the International Alliance of ALS/MND Associations.

“We are excited about the possibilities of arimoclomol as a potential new therapy in ALS and now look forward to reporting trial results in the first half of 2021,” Blaettler added.

Arimoclomol also is in clinical development for three other orphan diseases: Niemann-Pick disease Type C, Gaucher disease, and sporadic Inclusion Body Myositis.