Rare Daily Staff

Orphazyme reported positive top-line results for its phase 2/3 trial of arimoclomol for the treatment of patients with Niemann-Pick disease Type C (NPC), a rare and deadly lysosomal storage disorder.

NPC is a genetic, progressively debilitating, fatal neurovisceral disease. As a consequence of a genetic mutation, patients with the condition produce a misfolded NPC protein that prevents the body from clearing certain lipids. As these lipids build-up in tissues and organs, including the brain, it causes progressive damage. The estimated prevalence of NPC in the United States and Europe combined is 1,000-2,000. There are no approved treatments for NPC in the United States and only one approved product in Europe.

Arimoclomol 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, crosses the blood brain barrier. It has been studied in seven phase 1 and three phase 2 trials. Arimoclomol is in clinical development for NPC, Gaucher disease, sIBM, and ALS.

The phase 2/3 trial was a multi-center, prospective, double-blinded, placebo-controlled interventional study with a 12-month duration. In total, 50 patients were enrolled in the European Union and the United States. The purpose of the trial was to assess the efficacy and safety of arimoclomol, compared to placebo, in the treatment of NPC, administered in addition to the patient’s standard-of-care.

The study showed a 74 percent reduction in the progression on the primary endpoint using a measure known as the 5-domain NPC-CSS. A second measure of efficacy known as the CGI-I were lower than expected impeding the ability to show a positive effect.

“We are highly encouraged that the top-line data show a strong positive trend on the 5-domain NPC-CSS. We now look forward to receiving the full analysis of data,” said Anders Hinsby, CEO of Orphazyme. “In addition, the open-label extension trial will provide data on the clinical benefit of arimoclomol over a longer period of time. We are determined to make arimoclomol available to patients as quickly as possible.”

The overall incidence of adverse events was similar for arimoclomol (85.7 percent) and placebo (81.3 percent). Serious adverse events occurred less frequently in the arimoclomol group (14.3 percent) compared to placebo (37.5 percent).

Arimoclomol has been granted Orphan Drug Designation in the United States and European Union. The FDA also granted arimoclomol Rare Pediatric Disease Designation and Fast Track designation for the treatment of NPC.

Orphazyme said it will engage with the U.S. Food and Drug Administration and the European Medicines Agency to determine the best path towards making arimoclomol available to those suffering from NPC.

September 28, 2018
Photo: Anders Hinsby, CEO of Orphazyme

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