Rare Daily Staff

Orphazyme said a pivotal trial of arimoclomol in amyotrophic lateral sclerosis failed to meet its primary and secondary endpoints to show benefit in people living with the rare, neurodegenerative disease.

Shares of Orphazyme fell more than 30 percent on the news in intraday trading.

Topline data will be presented at the upcoming virtual European Network to Cure ALS meeting, May 12-14, and complete data from the study will be published later this year.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and always fatal disease. Protein misfolding and aggregation in motor neurons are hypothesized to be important contributors to the disease process, which ultimately leads to paralysis of skeletal muscles as well as the muscles that enable breathing. The patient population in Europe and the United States is estimated to be approximately 50,000 patients. Currently, there are only limited treatment options available. Arimoclomol has been granted Orphan Drug Designation in Europe and the United States for the treatment of ALS.

Arimoclomol is an investigational drug candidate that amplifies the production of heat shock proteins (HSPs). HSPs can rescue defective misfolded proteins, clear protein aggregates, and improve the function of lysosomes. Arimoclomol is administered orally, and has now been studied in 10 phase 1, four phase 2 and three pivotal phase 2/3 trials. Arimoclomol is in clinical development for Neimann Pick disease type C (NPC) and Gaucher disease. Arimoclomol has received orphan drug designation for NPC in the United States and European Union. Arimoclomol has received fast-track designation from the U.S. Food and Drug Administration for NPC. In addition, arimoclomol has received Breakthrough Therapy and Rare Pediatric Disease designations from the FDA for NPC.

“We are disheartened by these results, as we had hoped arimoclomol might represent a viable new approach against the formidable challenge of this devastating disease. We express our sincere thanks to the investigators, patients and families for their participation and collaboration in our program,” said Thomas Blaettler, chief medical officer of Orphazyme. “With over 18 months of evaluation, this trial represents one of the longest running clinical studies in this category. While unsuccessful, the data generated will contribute meaningfully to the scientific dialogue on this challenging disease.”

The randomized, placebo-controlled phase 3 trial was conducted among 245 patients at 29 sites in 12 countries in North America and Europe. Participants were randomized (2:1 ratio) to receive either arimoclomol or placebo for up to 76 weeks. The primary endpoint was to determine the efficacy of chronic treatment with arimoclomol compared to placebo in participants with ALS as assessed by the combined assessment of function and survival (CAFS). This endpoint was selected to illustrate the overall treatment effect based on survival and the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Secondary endpoints included survival, change in ALSFRS-R, and slow vital capacity (SVC).

Orphazyme’s applications for arimoclomol for Niemann-Pick disease type C are under priority review with the FDA, with an expected PDUFA action date of June 17, 2021, as well as with the European Medicines Agency, with an opinion from the Committee for Medicinal Products for Human Use (CHMP) expected later this year.

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