The journey of gene therapy discovery to the commercial market is a difficult and detailed one. Commercialisation requires a broad interface of scientific expertise, cutting-edge technologies, and advanced processes to bring the next generation of advanced therapeutics to the market. Currently, therapeutic cancer applications stand at the forefront of the field, surpassing treatments for neurological diseases, hepatological diseases, Duchenne muscular dystrophy, and other conditions. The global gene therapy market is estimated to grow at a Compound Annual Growth Rate (CAGR) of 27.8%, increasing from 3.8 billion USD in 2019 to 13.0 billion USD by 2024. Key players in the field include Novartis, Bluebird Bio, GlaxoKlineSmith, UniQure, Spark Therapeutics, and Kite Pharma. Despite the impressive CAGR forecast, gene therapy has yet to reach full market penetration, with some treatments, such as CAR-T cell therapy, having only a 20% patient eligibility rate.
Other critical challenges of commercialisation include adherence to demanding regulatory protocols and offsetting exponential manufacturing costs. Contrasting regulations and scale-up initiatives also pose a problem. There has been substantial investment to overcome the pressing and well-known difficulties of gene therapy commercialisation within recent years. In this article, we look at some of the solutions and highlights how best to navigate the various hurdles facing market penetration.
Regulatory Challenges of Gene Therapy Commercialisation
Rapid developments within the gene therapy field require equally fast-paced approvals. However, during the late stage of gene therapy development, the sometimes-contrasting policies of different regulatory bodies can become a bottleneck both to the quality control of new therapies and their advancement to the commercial market. The two most prevalent regulatory bodies are The European Medicines Agency (EMA) and The United States Food and Drug Administration (FDA). In determining market approval in different continents, the EMA and FDA produce different sets of guidelines. A senior representative of Bluebird Bio summarises the issue with the following words, “regulatory bodies have, we know, very different philosophical approaches, and this is especially the case in gene therapy”. This can be confusing and significantly impact the commercialisation process. In 2020, Bluebird Bio experienced such difficulty when their Zynteglo treatment for Beta-thalassemia received approval by the EMA but not the FDA. A direct consequence of this was the inability to meet patient and market demands. “We had a commitment and timeframe in which to bring the treatments to patients by a specific date, and we were late”, explains the representative from Blubird bio.
Navigation Strategy: Opportunity for Optimisation
When a drug product does not receive approval, further CMC testing is carried out. Drug manufacturers must return to the laboratory and continue to validate their approach for the regulatory body in question. “An unexpected silver lining of this setback is that you could end up submitting an even better product the second time around”, says our Bluebird Bio source. Rigorous testing can foster improved assurance with investors by increasing the therapy’s economic viability. Whilst swift approval may be preferable, a rapid approval process, most notably seen in the accelerated rollout of the COVID-19 vaccine, inevitably raises questions about efficacy.
CMC Challenges of Gene Therapy Commercialisation
To appropriately manufacture a pharmaceutical drug product, there must be clear definitions of product characteristics and product testing to ensure that the pharmaceutical is safe, effective, and consistent between batches. Vesselin Mitaksov, Senior Principal Scientist at Pfizer, notes, “you need to know what makes the product perform consistently and ensure that the right technologies are in place to ensure the drug candidate is as efficacious and risk-free as can be.” The problem with this, however, is that CMC can require large amounts of product volume. “When the batch sizes being developed are already small, you might be using 10% of the batch for testing”, John Madsen, Head of Plasmid DNA Development and Manufacturing at PTC Therapeutic, explains. This places a significant strain on resources and further increases manufacturing demands.
Navigation Strategy: Improved Communication
Using rapid tests of small-batch volumes is one way to navigate the high volume demands of CMC. Another possible workaround is to take a more collaborative and open regulatory approach. By improving communication with the regulatory body, manufacturers can negotiate volume levels. For Nick Li, Global/US Market Access Lead at uniQure, “starting the conversation earlier between regulatory liaisons and manufacturing company can ensure that the product is already optimised”. Early collaboration can provide valuable insights to address later stage commercialisation considerations. John Madsen speaks of the undeniable need to “really understand the drug development process so that you are not surprised when the regulators come in and start interrogating the safety and integrity of your product”. By strengthening communication strategies, it is possible to bypass potential setbacks and provides a swift and solid CMC framework.
Economic Challenges of Gene Therapy Commercialisation
Currently, around 96% of the gene therapy sphere is commercially owned. Although this indicates how the industry matures at a progressive rate, developing an achievable economy is another matter altogether. As Nick Li points out, “the lifetime cost for Haemophilia is well over $20 million, which is not affordable”. The challenge of commercial cost is a big one, and in the past has even led to the failure of some products which had to be removed from the market purely because they were not commercially viable. Failure to meet manufacturing, process development, and CMC demands will lead to lost industry opportunities and potentially have a cataclysmic impact on the evolution of the gene therapy field.
Navigation Strategies: Innovative Payment Plans and Real World Data
There are several ways to offset the high costs associated with cell and gene therapy commercialisation. Introducing innovative payment plans is just one way to overcome this hurdle and works by establishing outcome-based reimbursement payment models. Innovative payment plans are necessary to support the imitative of reducing costs as they can accurately access the value of gene therapy products. As a field with long-term outcome goals, the gene therapy arena should aim to also widen participation through implementing early-stage Real World Data strategies. The ability to combine clinical trial data and Real World Data is one of the most critical transformations occurring in gene therapy precision medicine. Real World Data can identify unmet clinical needs and predict heterogeneous patient responses.
Gene therapy commercialisation is a tricky but rewarding journey. As the market and demand for cell and gene therapeutics expands, so will the need to upscale. While upscaling is an inevitable by-product of market promise, its feasibility is not always easy due to steep costs. However, Nick Li identifies a silver lining of industry expansion, claiming how “as new players are entering the field every day; they will likely naturally bring the cost of manufacturing and commercialisation down”. Healthy industry competition may lead to a more impactful and achievable market economy. And with a more achievable market economy, we at Oxford Global expect to see the gene therapy industry reaching brand new heights.