Rare Daily Staff

The U.S. Food and Drug Administration notified Orphazyme that it would not approve its experimental therapy arimoclomol for the rare lysosomal storage disorder Niemann-Pick disease type C without additional data.

Niemann-Pick disease type C (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.

The agency said it needed qualitative and quantitative evidence to substantiate the validity and interpretation of the 5-domain NPC Clinical Severity Scale (NPCCSS) and, in particular, the swallow domain. A primary endpoint of the phase 2/3 clinical trial was progression in disease severity as measured by the 5-domain NPCCSS. This is a disease-specific measure of disease progression consisting of the five clinically most relevant domains to patients with NPC, caregivers and physicians.

The FDA also noted in its complete response letter to the company that additional data are needed to bolster confirmatory evidence beyond the single phase 2/3 clinical trial to support the benefit-risk assessment of the New Drug application.

Shares of Orphazyme fell to $7.92 in midday trading, more than a 45 percent drop on the news.

“We are disheartened by the outcome of the FDA’s review, given the urgent need for a new therapeutic option for NPC, but we remain committed to working with the regulators, with the goal of delivering arimoclomol to families managing this challenging disease,” said CEO Christophe Bourdon. “We will focus our efforts on pursuing the European regulatory approval, with CHMP opinion expected in Q4 2021 and potential Marketing Authorization in Q1 2022. We are assessing the potential path forward in the U.S. in partnership with the FDA. In the short-term, we will need to reduce our costs substantially and freeze all company efforts not related to clinical and regulatory activities to support approval for NPC.”

Photo: Christophe Bourdon, CEO of Orphazyme

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