As medical institutions develop the infrastructure for decentralized manufacturing of cell therapies, they are positioned to outperform big pharma’s limited success with a centralized approach to manufacturing.
A revolution is coming in the discovery, development and delivery of living medicines. This revolution is being led by well-funded, elite academic medical centers, such as the University of Pennsylvania, Fred Hutch, University College London, and other institutions across the US, Europe, South Korea, Japan and China. Almost all the approved cell and gene therapies have originated from such centers.
Advances in manufacturing infrastructure will enable these institutions to play a more substantial role in the value chain of living medicines, from research to commercial product. Indeed, once the manufacturing infrastructure is in place, we will likely see elite medical centers and their manufacturing partners, rather than big pharma, become the major players in the development and commercialization of cell and gene therapies.
Over 9,900 cell therapy trials are currently recruiting. No doubt many of these trials will fail, but if the past is any guide, five to ten per cent will succeed, meaning a significant number of cell therapies will be approved in the near future. In an often-quoted statement, the former commissioner of the Food and Drug Administration (FDA), Scott Gottlieb, predicted that, by 2025, the FDA would approve between 10 and 20 cell therapies per year. This is an extraordinary number when one considers that the total number of drugs approved in a single year over the last ten years has averaged around 40. This opportunity is being recognized by investors, who pumped €17.7B ($20B) into cell and gene therapies in 2020, eclipsing the total invested in 2019 and ending up nearly 50% higher than the previous record of €12B ($13.5B) set in 2018.
The main challenge for most cell and gene therapy programs, however, is the lack of distributed manufacturing infrastructure that would allow the translation of cutting-edge cell therapies into affordable treatments that are available to patients anywhere. Big pharma has attempted to solve this with massive investments in centralized manufacturing. Catalent has recently bolstered its centralized manufacturing by spending over €1.3B ($1.5B) acquiring the CDMOs Paragon Bioservices and MaSTherCell, while both Novartis and Kite have purchased or built major manufacturing facilities.
However, this capital-heavy approach is a dead end. Economically, it doesn’t work; the cost of centralized, manual processes will keep therapies out of reach for patients and payers. A recent example was bluebird bio’s withdrawal of Zynteglo, a gene therapy for a rare blood disorder, from the German market because it could not agree on a price with the health authorities. This centralized approach also doesn’t work from a clinical perspective because of complicated logistics, time lags, and failed batches.
While centralized manufacturing might be suitable for allogeneic cell therapies using cells from donors, they will still be produced in small batches and are years away from materializing. Autologous therapies, using the patient’s own cells, are the here and now of cell therapy. They are likely to remain the best option for many patients for decades to come if they can be done cheaply at scale, and where patients are located.
With advances in gene editing and cell culturing, the final barrier to unleashing this revolution is the lack of a cloud-connected, automated, and flexible manufacturing system that would make it possible to create living medicines consistently according to good manufacturing practice standards. This barrier is about to come crashing down as a wave of new companies like Ori Biotech, National Resilience, G-CON Manufacturing, Apprentice.io and others bring new products, services, and business models to market that will make the distributed discovery, development, and manufacturing of gene-edited cell therapies possible and scalable.
The growth of distributed manufacturing of cell therapies was recently recognized by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) in a request for comment on regulations for distributed manufacturers. The MHRA rightly recognizes that providing a regulatory framework for distributed manufacturing will enable an entirely new pharmaceutical industry to emerge. It is no longer a question of if distributed manufacturing of gene-edited cell therapies will emerge as a new modality, but when and how quick and deep this adoption will be.
This process is being driven by bottom-up innovation at elite medical centers. These centers, such as the Memorial Sloan Kettering Cancer Center and MD Anderson, are already developing their own therapies and delivering them on an experimental and compassionate basis to hundreds of patients. Many more patients benefit from these therapies than the few who get the FDA-approved treatments being marketed for $1M a pop by the likes of Gilead Sciences and Novartis.
With the right manufacturing and data infrastructure in place, these elite medical centers can also become therapeutic developers. With the ability to produce consistently and comparably across stages of development and geography, they will be able to get approval of their therapies and market them. The entire connected network of distributed manufacturing will be able to spread learning instantly to ensure maximum safety and efficacy. For example, a large medical centre in Lagos, Nigeria could be using the latest bioprocessing innovations developed at MD Anderson the day before. And MD Anderson could benefit from the data created in Lagos.
The vision is a grand one that doesn’t fit with big pharma’s current model. Unless big pharma gets onboard with new trends, it is unlikely to have much of a role in the living medicines space. Instead, the industry will be built around partnerships between major elite medical and research centers, investors, and a new category of companies that offer the management of living medicines as a service. There will be many winners, but hopefully the biggest winners will be the patients who will be able to access a new generation of therapies.
Jonathan Hay is a Partner at Delin Ventures, a UK-based VC firm that invests in breakthrough life science and technology businesses.