LogicBio Therapeutics, Inc. has received an orphan drug designation from the FDA for LB-001, a recombinant adeno-associated viral vector with human methylmalonyl-COA mutase (MUT) gene, for the treatment of methylmalonic acidemia (MMA).
LB-001, an investigational pediatric genome editing therapy, is based on LogicBio’s GeneRide™ technology, which enables site-specific integration and lifelong expression of therapeutic transgenes without using exogenous promoters or nucleases. LB-001 is designed to incorporate a functioning version of the faulty MUT gene into the patient’s genome.
LogicBio demonstrated preclinical proof-of-concept of GeneRide in multiple animal models of the disease, improving survival and reversing disease pathology. In preclinical MMA models, when GeneRide inserted a transgene into cells, they demonstrated a selective survival advantage over cells not expressing the transgene.
The rare methylmalonic acidemia, an autosomal recessive disease, begins in early childhood. It prevents the proper processing of certain fats and proteins, which results in a toxic buildup of metabolites that can cause life-threatening decompensations in infants and children. This can lead to significant morbidity and mortality, including infections, neurodevelopmental disabilities, and chronic kidney disease.
MMA is inherited in an autosomal recessive pattern; both copies of the MMUT, MMAA, MMAB, MMADHC, or MCEE gene in each cell have mutations. Typically, parents of affected individuals carry one copy of the mutated gene but they do not show signs and symptoms of the condition.