FDA Grants Rare Pediatric Disease Designation for Huidagene’s CRISPR Therapy for MECP2 Dup Syndrome

Rare Daily Staff

The U.S. Food and Drug Administration granted both Orphan Drug and Rare Pediatric Disease designations to Huidagene’s HG204, a CRISPR RNA-edited experimental candidate for the treatment of MECP2 duplication syndrome.

Methyl-CpG binding protein 2 (MeCP2) duplication syndrome (MDS) is a rare, fatal childhood neurodevelopmental disorder with an estimated live birth prevalence in males of 1 per 150,000. MDS is one of the most common sub-telomeric genomic rearrangements in males, accounting for about 1-2 percent of X-linked cases of intellectual disability. MDS, which is caused by the duplication or triplication of the MECP2 gene, manifests predominantly in boys and is characterized by infantile hypotonia, developmental delay, intellectual disability, anxiety, loss of motor skills and speech, epilepsy, recurrent respiratory tract infections and shortened lifespan, with death often occurring before the age of 25 years. There are no approved disease-modifying therapies for MDS and current treatments for MDS include symptom management and supportive care.

HG204 is developed using a single adeno-associated viral (AAV) vector delivering a novel CRISPR/high-fidelity Cas13Y and gRNAs targeting MECP2 (gMECP2). HG204 is stably expressed in brain regions of mice and monkeys where the pathological changes of MDS mainly occur. Huidagene’s extensive preclinical studies using AAV-hfCas13Y-gMECP2 in humanized MDS mouse model demonstrated significant reduction of MeCP2 protein and reversal its disease features.

“Although there is currently no clinical trial evaluating MDS, this is a sign of recognition for MDS and raises hopes for children and teens with this fatal, devastating disorder,” said Alvin Luk, co-founder and CEO of HuidaGene. “We very much hope that HG204 can make a difference to children and families affected by MDS, and we will be working closely with clinicians, researchers, and FDA to determine the optimal way to move the drug forward.”

The FDA grants Rare Pediatric Disease designation to incentive development of new treatments for serious or life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people affected in the U.S. The RPDD program allows for a sponsor who receives an approval to qualify for a priority review voucher (PRV) that can be deemed to receive an expedited six-month priority review for any subsequent marketing application or may be sold or transferred. Most recently, Sarepta Therapeutics sold a PRV for $102 million.

Photo: Alvin Luk, co-founder and CEO of HuidaGene