Orphazyme Receives FDA Complete Response Letter for Rare Disease

Denmark-based Orphazyme recently announced that FDA issued a complete response letter regarding its heat shock protein amplifier, arimoclomol, intended for Niemann-Pick disease type C (NPC), a rare inherited disease. 

In the letter, FDA stated that it needed additional qualitative and quantitative evidence to further substantiate the validity and interpretation of the 5-domain NPC Clinical Severity Scale (NPCCSS), particularly the swallow domain.

NPCCSS is a disease-specific measure of disease progression consisting of the five clinically most relevant domains to patients with NPC, caregivers, and physicians, an Orphazyme spokesperson explained. 

The primary endpoint of the Phase 2/3 clinical trial was progression in disease severity measured by the 5-domain NPCCSS.

FDA also stated that additional data is needed to advance confirmatory evidence beyond the single Phase 2/3 clinical trial to support the benefit-risk assessment of the new drug application.

“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,” Christophe Bourdon, CEO of Orphazyme said in the announcement. 

Bourdon stated that the company will focus on pursuing the European regulatory approval, with opinion from the Committee for Medicinal Products for Human Use expected in Q4 2021  and potential marketing authorization early next year.

“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,” he said. 

NPC is a rare genetic neurovisceral disease caused by mutations leading to defective NPC protein. The incidence of NPC occurs in one in 100,000 births, and there are nearly 1,800 individuals in the US and Europe living with the disease. 

Currently, there is no approved treatment for NPC in the US. 

In September, Orphazyme announced that FDA accepted, with priority review, the company’s new drug application for arimoclomol for NPC treatment. 

This designation shortens the review period from ten months to six months from the acceptance of the NDA. 

FDA set a target action date of March 17, 2021, under the Prescription Drug User Fee Act (PDUFA). So far, arimoclomol has been granted FDA fast track and breakthrough therapy designations for NPC as well as orphan drug and rare pediatric disease designations.

Joslyn Crowe, executive director of the National Niemann-Pick Disease Foundation, stated in the September announcement that FDA’s acceptance of the arimoclomol filing is another “major step forward” in the effort to bring a treatment to individuals affected by NPC.