Results, Setbacks

Their lead drug failed both main goals in key study, but Orphazyme plans to pitch subgroup analyses to regulators

Orphazyme attempted on Wednesday to enthuse investors about the results of a Phase II/III study testing their lead drug, arimoclomol, in patients with a rare genetic disorder, underscoring some positive subgroup analyses — even though the experimental treatment missed its primary endpoints. The company is now preparing marketing filings and planning to engage with regulators to get arimoclomol on the market at the earliest.

The company’s shares (CPH: $ORPHA) shot up about 40% in response on Wednesday, but climbed down about 5% on Thursday afternoon GMT.

The drug is being evaluated for use in Niemann-Pick disease Type C (NPC), an inherited neurodegenerative disease characterized by the body’s inability to transport cholesterol and other lipids inside of cells that causes an abnormal accumulation within various tissues including the brain. In the 12-month study, 50 patients between the age of 2 and 18 were given either arimoclomol or placebo on top of standard of care.

The company highlighted subgroup analyses that suggest the drug has a significant impact on the disease. But that comes after the company acknowledged months ago that the drug failed the primary endpoint.

Anders Hinsby

“With this highly compelling data set, we are looking forward to working with regulatory authorities to make arimoclomol available to patients as fast as possible,” Orphazyme chief Anders Hinsby said in a statement.

The trial had two primary endpoints tracking disease progression: the 5-domain NPC Clinical Severity Scale (NPC-CSS), a disease-specific outcome measure, as well as Clinical Global Impression of Improvement scale (CGI-I), a self-rating tool, at the behest of the FDA.

In terms of NPC-CSS, the company said treatment with arimoclomol adjunct to routine clinical care resulted in a 74% reduction in disease progression, but the p-value at 0.0506 indicated the effect was not statistically significant. But researchers claimed that two subgroup analyses offered stronger conviction of the drug’s potential benefit. When looking at patients 4 years or older (44/50), treatment progression slowed in patients on arimoclomol versus placebo, with a p-value of 0.0219. Another subgroup analysis, requested by the EMA, showed that arimoclomol had a significant impact compared to a placebo in patients who got miglustat — originally sold by Actelion under the brand name Zavesca — as part of standard care, with a p-value of 0.0071.

On the CGI-I endpoint, an inflated placebo response deterred the drug from demonstrating an impact on the main goal, the company said, adding that when considering patients who severely progressed during the trial, only 10.7% of arimoclomol-treated patients got “much worse” or “very much worse” compared to 26.7% in the placebo control group.

Other subgroup analyses also suggested a lack of statistical significant improvement with the drug, although some exploratory biomarker data were favorable to arimoclomol.

Safety data were also positive, with serious side-effects occurring less frequently in the arimoclomol group (14.7%) compared to placebo control (37.5%).

The ball is now in the regulatory court, but considering NPC is a rare disease affecting an estimated in 1/120 000 live births, it could go either way.


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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
Marketing Associate - Demand Generation
Catalytic Data Science Charleston, SC
Associate Principal, Life Sciences Partnerships
Flatiron Health New York City or San Francisco

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