Gene therapy CDMOs play critical role in enabling AAV process improvement & standardization
Posted: 3 September 2024Wes McConnell, CFO at Ascend
The approval of numerous gene and gene-modified cell therapies by regulatory agencies around the world, and most notably FDA and EMA in the US and Europe, has supported the use of viral vectors for the safe and effective delivery of genetic material both in vitro and in vivo.
Of the various types of vectors employed for these therapies, adeno-associated viruses (AAVs) have emerged as a favored in vivo gene therapy vector due to their nonpathogenic nature and safety profile, as well as the availability of differing serotypes.
To date, seven AAV-based gene therapy products have been approved by either FDA or EMA, and over 300 preclinical and clinical candidates are currently under development. For many indications, these therapies offer the potential for durable, possibly lifelong curative treatments from a single administration.
However, the promise of AAV gene therapies is tempered by manufacturing challenges in scalability, yield, and quality, as well as the cost of production of AAV-based therapies. Efforts are ongoing across the industry to develop robust processes that are scalable and consistently exhibit high productivity and generate high-quality vectors. However, in early stages, there are still high costs and operational demands that can make gene therapies often reach millions of dollars per treatment.
A market in evolution
Industry growth has recently been stalled by a lack of attractive financing across the small molecule, large molecule, and advanced therapies sectors. But in the cell and gene therapy sector progress has been further hindered by a lack of available and scalable technologies for production.
Most AAV-based gene therapy is driven by small and emerging biotech firms that will require technology suitable from development to commercialization under GMP conditions. This can be challenging to source in the current market, and costly to bring in house.
At Ascend, we have seen this firsthand as biotech product companies coming out of the 2020/2021 biotech boom had built their own in-house (and underutilized) capacity. Unfortunately, this required capital that would have otherwise advanced these programs and supported the delays in pipeline development programs at a time when the biotech market was contracting.
In response to these challenges, the FDA has encouraged early-stage companies to transition their manufacturing processes to contract development and manufacturing organizations (CDMOs) that have established innovative platform manufacturing solutions.
Significant simplification and cost reduction in viral manufacturing technologies is continuing to happen in real time but can be hard to access for small biotechs. CDMOs can be part of pilot programs and can receive expedited access to in-demand technologies that may be harder for a small company to acquire quickly.
Outsourcing for success
Given the growing numbers of small and emerging biotech/biopharma companies developing novel AAV-based gene therapies for a broadening array of indications, it is not surprising the global market for AAV vector manufacturing services is projected to expand at a compound annual growth rate of nearly 21% through 2029.1
Gene therapy developers that leverage the services of CDMOs with demonstrated expertise in AAV vector development and manufacturing avoid the need to make large capital investments on production capabilities for unproven candidates. Working with innovative CDMOs also ensures access to state-of-the art proprietary manufacturing solutions that streamline AAV production, reducing the time and cost to bring new AAV-based gene therapies to market. Access to advanced analytical capabilities supporting robust product and process development and product release is another advantage.
CDMOs with experience shepherding projects from preclinical to IND and on to BLA filings also provide invaluable compliance expertise and guidance within a complex and dynamic regulatory environment. It is best to work with CDMO that can be a CMC partner and has the integrated solutions and knowledge to help on the development journey. This is critical when working in these specialized modalities where developers have diverse needs and tight timelines.
A quality-driven approach
Ascend was built forward from therapeutic companies like Spur Therapeutics and Beacon Therapeutics. Having roots in therapeutic development means we operate a little differently than a standard CDMO. Site leadership and teams have a “been there done that” experience level.
Our team is continuously evolving a modular AAV production platform of proprietary and sourced technologies. We are highly focused on a quality first approach to balance quality and yield from concept to commercialization and can offer end-to-end support or standalone services. Our EpyQ™ AAV production system leverages a dual plasmid approach (as an alternative to triple transfection, which we also offer) to optimize AAV production.
At Ascend, we are inspired to enable today’s developers to realize the full potential of AAV-based therapies and vaccines. If you are interested in working with a partner like this, reach out any time at business@ascend-adv.com or to learn more about what we are up to at https://www.ascend-adv.com/news-and-insights/.
Reference
Mordor Intelligence, “Adeno-Associated Virus (AAV) CDMO Market Size & Share Analysis - Growth, Trends & Forecasts (2024-2029),” https://www.mordorintelligence.com/industry-reports/adeno-associated-virus-aav-cdmo-market