Recent improvements in our understanding of the human genome, together with advanced DNA editing and analytical tools, position the cell and gene therapy market for explosive growth over the coming decade. However, these technologies have significant formulation development, cGMP manufacturing and aseptic filling challenges, which must all be overcome before this potential can be fully commercialized. The engagement of a CDMO partner with a broad portfolio of delivery technologies, a strong formulation track record and manufacturing flexibility is the preferred pathway for success within this highly specialized area.
A portfolio of technologies is now available for companies seeking to create the next wave of gene and cell therapies. The first chimeric antigen receptor (CAR)-T cell immunotherapy was FDA approved in 2017. The first RNA interference (RNAi)-based gene therapy for the treatment of hereditary ATTR (hATTR) amyloidosis, a rare disease, was approved in 2018. The year 2020 marked the emergency use authorization of the first mRNA vaccine for COVID-19, and the awarding of the Nobel Prize in chemistry to some development leaders of the CRISPR/Cas9 gene editing technology. Such technologies are poised to push ex vivo and in vivo treatment opportunities into a new era of growth over the decade.
However, the advanced formulation technologies that are required for targeted delivery of these therapies, as well as sophisticated process and filling equipment that are essential for cGMP manufacturing, means that the path to clinical scale-up and commercial launch will remain very challenging for aspiring companies.
In particular, cell and gene therapy products face unique formulation and process development challenges throughout each step in the drug commercialization and manufacturing process. Whether they are composed of proteins, nucleic acids or membranes, each therapy is highly complex, biologically active and novel in design. The choice of delivery technology and process development pathway will have a major impact on optimizing the safety and efficacy of the final drug product.
The selection of delivery technology for gene therapies will typically come down to the type of payload and the target site. Viral vectors such as adeno-associated virus (AAV), adenovirus, lentivirus and retrovirus are being closely studied for their ability to deliver genetic material into a cell. These systems represent promising candidates for the genetic treatment of cancer, AIDS, neurological and cardiovascular disorders as demonstrated in 2017 when FDA approved an AAV-based product for Leber congenital amaurosis.
Non-viral gene delivery systems for nucleic acids such as DNA and mRNA are primarily delivered via lipid-based and other nanoparticle technologies. Due to their low immunogenicity, capacity to deliver a large genetic payload, and efficient scalability, the market for these non-viral gene therapies is poised to grow with a 22.6% compound annual growth rate (CAGR) to reach $4.9 billion in 2023, according to a 2018 BCC Research market report.
Beyond their use for large populations, gene therapy, stem cell or CAR T-cell therapy, gene modification and gene editing technologies have strong opportunities for the treatment of specific subtypes of cancer or rare diseases, of which more than 7,000 have been identified to-date. Of these rare diseases, around 80% are caused by genetic defects, and very few offer attractive treatment options beyond supportive and symptomatic care.
For such indications with well-defined populations, manufacturing volumes for clinical and commercial scale batches will, by definition, be extremely small. Modular, scalable process equipment, such as LIPEX® extruders from Evonik or microfluidic systems can be typically customized for such low-volume / high-mix manufacturing projects.
Furthermore, the novel filling and low batch size requirements for such therapies will in many cases comprise modular platforms that possess the necessary flexibility to load the drug product into a vial or other primary container such as a prefilled syringe. The VarioSys® platform from Bausch + Stroebel is one such flexible automated system that can support the aseptic filling of parenteral drug products, in powder, liquid, suspension or combination form.
Most CDMOs specialize in only one drug delivery technology platform, restricting the options available to a customer for formulation and process development. Furthermore, few CDMOs have a strong historical track record with similar projects that could provide reassurance to the customer and reduce overall risk. Lastly, only a very small selection of CDMOs can support customers throughout the entire process from initial formulation feasibility to scale-up and cGMP commercial production.
Evonik is one such CDMO, with a broad portfolio of non-viral delivery technologies suitable for gene-based therapies, with more than 30 years of clinical and commercial expertise across a range of nanomedicine areas. With a multitude of internal process technologies and other capabilities to support manufacturing via extrusion, microfluidic, microencapsulation and other manufacturing processes, and FDA-registered manufacturing sites and aseptic filling lines, Evonik is well positioned to serve as a reliable partner for companies with next generation therapeutic approaches