7:37 PM
 | 
Sep 13, 2018
 |  BC Innovations  |  Product R&D

Academia’s manufacturing problem

How gene therapy manufacturing bottlenecks are impeding academic translation

Editor's Note: This article was updated on Sep 14, 2018 at 6:32 PM PDT

With backups at academic manufacturing centers beginning to hamper translation of early stage gene therapies, pushing those who can afford it to CMOs, at least one non-profit has stepped in with a model to deliver the services on the cheap. But without more, the field may be slow to benefit from the next generation of gene therapies coming through.

Gene therapies are notorious for scale up issues that can hinder late stage trials or commercialization. However, manufacturing difficulties also extend to preclinical development, in particular in the transition from animal proof of concept to IND-enabling studies. The former does not require GMP-like vector, but the latter does.

Academic researchers typically have two options for obtaining high enough quality vector, and sufficient quantities, for IND-enabling work: use a specialized vector production core at a large academic institution, of which there are few; or compete with drug companies that are capable of paying more for limited manufacturing slots at CMOs.

With FDA’s first-ever approval of an in vivo gene therapy in December, Spark Therapeutics Inc.’s Luxturna voretigene neparvovec, the field is on the rise. Academic and industry researchers alike are pushing the modality’s horizons, moving gene therapies beyond the small volume compartment of the eye, where Luxturna is delivered, into larger organs and into indications that require systemic administration, which necessitates orders of magnitude more vector.

University production cores now have long lines that are pushing some researchers to seek more expensive CMO services, which in most cases requires dipping into grant money that isn’t allocated for that purpose.

NIH is still backing the search for new gene therapies, according to Jaysson Eicholtz, director of GMP operations at Nationwide Children’s Hospital. “We’re still seeing good NIH funding going to programs, but those dollars aren’t stretching quite as far,” he told BioCentury.

“Are CMOs going to be able to provide the material they need at a price they can afford, and at a timeline appropriate for innovative research?”

Kenneth Cornetta, Indiana University

At a joint FDA and National Center for Advancing Translational Sciences (NCATS) workshop held on Aug. 20 to discuss bottlenecks in gene therapy development, Jude Samulski, a pharmacology professor and director of the University of North Carolina at Chapel Hill Gene Therapy Center, called upon NIH to provide more funding for vector manufacturing so that researchers at smaller institutions or foundations won’t be left behind.

“If we end up with a structure of haves versus have nots, we will see a lot of orphan diseases not being tested because they won’t meet the commercial thresholds most companies have to play by,” he said. And many companies are not willing to pick up a gene therapy based only on animal POC.

The problem might ease as the field builds capacity and develops techniques to make vector manufacturing more efficient. In the meantime, at least one non-profit, Odylia Therapeutics, is offering alternative manufacturing support that could provide one solution. Still, as Odylia is focused on eye diseases, there’s a need for many others like it.

Preclinical pinch

For gene therapies, manufacturing considerations remain one of the greatest challenges in preclinical development.

In remarks to the Alliance for Regenerative Medicine’s annual...

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