Orphazyme Partnership to Run Through Extension of Phase 3 Arimoclomol Study

Orphazyme announced that it and Worldwide Clinical Trials will continue their collaboration through the long-term extension of a Phase 3 study into arimoclomol, a potential oral treatment for amyotrophic lateral sclerosis (ALS).

ORARIALS-01 is a randomized, placebo-controlled and double-blind trial (NCT03491462) underway at 30 centers across North America and Europe. It is assessing the efficacy and safety of arimoclomol capsules in 245 adults with ALS who first experienced weakness — defined as limb weakness, swallowing/speech problems, or shortness of breath — within 18 months of the study’s start.

The trial is now fully enrolled, and began dosing of a first person in August 2018. Following a screening/baseline stage, patients are randomized 2:1 to either arimoclomol or placebo for 76 weeks. Up to 18 patients on stable treatment with Radicava (edaravone), by Mitsubishi Tanabe, will also join the study in the U.S.

Its primary goal is measures of arimoclomol’s effectiveness, determined through a combined assessment of function and survival. Secondary goals include changes in the ALS Functional Rating Scale, slow vital capacity (a measure of lung function), and the time until patients need permanent assisted ventilation. Topline results are expected in the first half of 2021.

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Orphazyme, based in Denmark, entered into a partnership agreement with Worldwide, a global contract research organization, in late 2017, due its niche expertise in running clinical trials into rare diseases and those of the central nervous system (the brain and spinal cord), it said in a press release.

Patients who complete ORARIALS-01 will be eligible to continue or start treatment with arimoclomol in the open-label study (NCT03836716) that’s due to finish by August 2020.

ALS is marked by the clumping of misfolded (abnormal) proteins in specialized nerve cells that control movement, called motor neurons. Arimoclomol is intended to clear these protein clumps by increasing the production of heat-shock proteins, which amplify the function of lysosomes — cellular structures that break down unwanted materials, including excess or worn-out cell parts.

Arimoclomol is able to cross the blood-brain barrier, which protects the central nervous system from invaders like viruses that can be carried in blood circulation. It has been granted orphan drug designation in the U.S. and E.U. as a potential ALS treatment.

Arimoclomol is also being investigated as a therapy for patients with Niemann-Pick disease Type C, Gaucher disease, and sporadic inclusion body myositis.