OPMD is caused by a mutation of the poly(A)-binding protein nuclear 1 (PABPN1) gene. The resulting faulty protein can form insoluble aggregates associated with muscle weakness.
In a study published last year in the journal Nature Communications, Benitec showed that a molecular biology strategy known as DNA-directed RNA interference (ddRNAi) might be used to shut down and replace the mutant PABPN1 protein. The approach simultaneously inhibits the mutated protein and produces a functional protein to replace it with.
The ddRNAi approach led to a significant reduction in PABPN1 aggregates, reversing impaired muscle strength and decreasing muscle fibrosis. In their study, researchers used cells from OPMD patients to confirm results seen in mice and concluded the approach could be used to treat the orphan disease.
Based on these findings, Benitec and collaborators developed BB-301, a ddRNAi therapy for OPMD.
The FDA’s orphan drug status granted to BB-301 will provide the biopharmaceutical company with a range of benefits, from accelerated regulatory review and tax credits, as well as seven years of market exclusivity. The FDA’s orphan drug status follows the European Medicines Agency’s (EMA) decision to grant orphan designation to BB-301 one year ago, in January 2017.
“We are very pleased to have received Orphan Drug Designation from the FDA for BB-301, as it is another significant step forward for a key program in our pipeline,” Greg West, CEO of Benitec, said in a press release.
“We believe BB-301 represents a promising new approach for the treatment of OPMD and has the potential to make a meaningful impact for patients who have this debilitating disease,” he said. “The Benitec team is focused on executing our plan to advance BB-301 into human clinical trials by the end of 2018.”
Benitec completed pre-Investigational New Drug (pre-IND) application meetings with the FDA, EMA and Health Canada last year. The purpose of the meetings was to discuss the regulatory strategy for BB-301 as a treatment for OPMD and to ensure Benitec’s development program addressed the agencies’ expectations and requirements.
“We also believe this program, if successful, can act as a proof of concept for using our groundbreaking ‘silence and replace’ technology for other therapeutic targets potentially expanding market opportunities for Benitec and paving the way for the development of other monogenic orphan disease programs in the future,” West said.
Benitec is currently conducting preclinical and safety studies of BB-301, and plans to file a full IND application with the FDA in the final quarter of 2018.