Denali's Hunter Syndrome Candidate Receives FDA Orphan Drug and Rare Pediatric Disease Designations

Denali Therapeutics Inc. has announced that the FDA has granted orphan drug status and a rare pediatric disease designation to its pipeline candidate, DNL310, aimed at treating mucopolysaccharidosis II (MPS II), also known as Hunter Syndrome. This condition is a lysosomal storage disease caused by a deficiency in the IDS enzyme.

Denali plans to begin a phase I/II study on DNL310 for treating Hunter Syndrome in 2020. In earlier pre-clinical studies, DNL310 demonstrated increased brain uptake in a relevant disease model and a robust reduction of downstream markers of disease in the central nervous system compared with standard enzyme replacement therapy (ERT).

The orphan drug designation is granted to drugs capable of treating rare diseases that affect fewer than 200,000 people in the United States. This designation provides Denali with benefits including tax credits related to clinical trial expenses and an exemption from the FDA user fee. Upon regulatory approval, DNL310 will also be eligible for seven years of marketing exclusivity in the United States.

The rare pediatric disease designation offers Denali the opportunity to obtain a pediatric disease Priority Review Voucher from the FDA after the candidate’s qualifying new drug application (NDA) is approved for the treatment of any rare pediatric disease. This voucher can be used to procure a priority review for a subsequent NDA.

DNL310, administered intravenously, is being developed to improve the clinical indication of Hunter Syndrome, including neurological symptoms, which are not adequately addressed by currently approved therapies. The candidate utilizes Denali’s proprietary blood-brain barrier crossing enzyme transport vehicle (ETV) technology.

Denali is also leveraging its TV technology to develop a broad portfolio of biologic drug candidates, with two additional ERT programs initiated based on pre-clinical proof of concept with DNL310.

It's important to note that other companies, such as Sangamo Therapeutics, are also developing therapies for MPS II, including a phase I/II study of its zinc finger nuclease (ZFN) in-vivo genome editing candidate, SB-913.