Gene Therapy for OPMD Nears Human Studies, Benitec Announces

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New gene editing strategy

A single gene therapy that silences the mutation responsible for oculopharyngeal muscular dystrophy (OPMD) and replaces the mutated gene with a normal one may advance into human studies in the second half of 2018.

Benitec Biopharma started its OPMD program in 2014 and now announced their clinical candidate BB-301 as a one-step gene therapy approach.

OPMD patients develop muscle weakness in the upper eyelids and throat in adulthood, typically after age 40. OMPD is a rare genetic disease caused by a mutation of the poly(A)-binding protein nuclear 1 (PABPN1) gene. Because it affects fewer than 200,000 people nationwide, OMPD is considered an orphan disease that benefits from encouraging programs for drugs targeting these rare diseases.

In collaboration with research groups in London and Paris, Benitec tested a genetic approach known as DNA-directed RNA interference (ddRNAi) to shut down and replace the mutant PABPN1 gene using two different viral vectors. In this pre-clinical study, researchers found that the two-vector system restored muscular function in A17 mouse model, which displays many OPMD clinical signs including fibrosis and loss of muscle strength.

Now, Benitec combined “silence and replace” gene functions into a single vector (a carrier system) in a new clinical candidate, BB-301. Using a single vector, they succeed in eliminating 88 percent of the mutant gene product while restoring the normal gene function up to 90 percent. As a single product, BB-301 simplifies the regulatory process and the clinical strategy for human studies.

“This is an important development in our OPMD program. The single vector system shows the same excellent activity as the earlier generation dual vector system where the ‘silence and replace’ constructs were delivered in separate vectors. Similar application of the single vector technology may allow development of novel therapeutics to treat other orphan diseases. OPMD is a significant commercial opportunity for Benitec and we are working with the regulators and key opinion leaders in this field to advance BB-301 into the clinic as quickly as possible, ” Greg West, CEO, explained in a press release.

Benitec is in discussions with a broad group of OPMD clinicians and experts about a clinical trial that will be proposed to regulatory agencies later this year. If approved by the U.S. Food and Drug Administration, human studies could start in 2018.