NIH, FDA lead partnership to speed gene therapy research

The US National Institutes of Health (NIH), the FDA and a number of drugmakers and non-profit organisations formed a partnership to speed development of gene therapies, with a particular focus on improving understanding of adeno-associated virus (AAV) vectors. Joni Rutter, acting director of the NIH's National Center for Advancing Translational Sciences (NCATS), said the Bespoke Gene Therapy Consortium (BGTC) "aims to make it easier, faster and less expensive to pursue bespoke gene therapies…to incentivise more companies to invest in this space."

The partners noted that while there are approximately 7000 rare diseases, only two heritable conditions currently have FDA-approved gene therapies. "Most rare diseases are caused by a defect in a single gene that could potentially be targeted with a customised…therapy that corrects or replaces the defective gene," noted outgoing NIH director Francis Collins. "There are now significant opportunities to improve the complex development process for gene therapies that would accelerate scientific progress," Collins added.

Standardised model to speed work

While current gene therapy development is highly complex, time consuming and expensive, BGTC suggested that "a standardised therapeutic development model that includes a common gene delivery technology could allow for a more efficient approach." Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, remarked "by leveraging on experience with a platform technology and by standardising processes, gene therapy product development can be accelerated."

BGTC researchers will focus on examining the biological and mechanistic steps involved in AAV vector production, vector delivery of genes into human cells and how therapeutic genes are activated in target cells. It is hoped that the findings will provide important information for improving the efficiency of vector manufacturing and enhancing the overall therapeutic benefit of AAV gene therapy.

The gene therapy field has been plagued by a number of recent setbacks, with many involving the use of AAV vectors. Last month, Pfizer was forced to amend the study protocol for a trial of fordadistrogene movaparvovec in Duchenne muscular dystrophy after reports of muscle weakness, while Astellas also recently disclosed the death of a fourth patient in a study of its experimental gene therapy AT132 for X-linked myotubular myopathy. BioMarin Pharmaceutical has had to put a phenylketonuria trial of its gene therapy BMN 307 on hold as well because of liver tumours seen in preclinical testing.

Partnership to support clinical studies

Meanwhile, BGTC-funded research will also support between four and six clinical trials, each focused on a different rare, single-gene disease that currently has no commercial programmes in development. The studies are expected to employ different types of AAV vectors that have been used before in clinical testing in an effort to shorten the path from animal models of disease to human trials.

Along with the NIH and the FDA, partners of BGTC include Biogen, Johnson & Johnson, Novartis, Pfizer, Regenxbio, Roche's Spark Therapeutics unit, Takeda, Taysha Gene Therapies, Thermo Fisher Scientific and Ultragenyx Pharmaceutical.

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