"From growing cells to growing pains: navigating new obstacles in cell & gene therapy". That was the headline for the virtual Fierce Biotech Cell and Gene Therapy event that took place on 19 October.
The event included a stellar line-up with a mixture of panel sessions and interviews with executives from companies leading in the cell and gene therapy space. Speakers included John Leonard, M.D. (President and CEO of genome editing company, Intellia Therapeutics), Bobby Gaspar (CEO and Co-Founder of gene therapy company Orchard Therapeutics) and Mike Fraser (GM of Europe, Middle East and Africa at Novartis Gene Therapies) as well as representatives from companies such as Regenxbio, Catalent and Legend Biotech, to name but a few.
One of the key themes that ran through the event was manufacturing and its associated challenges. The last couple of years has seen companies across the sector clamouring for manufacturing capacity as demand for CDMO services has surged. Coupled with a shortage of viral vectors this has led to bottlenecks in manufacturing. This has highlighted the need for companies to do more longer term planning for their manufacturing strategy, capacities and supply chain logistics; a task that is not easy for new entrants to the space but will be crucial to avoid road blocks further down the line. The recent squeeze on manufacturing capacity has also been accompanied by a skills shortage in CGT manufacturing and, despite new initiatives to train more workers in this space, speakers at the event were also of the view that there is a need for continued automation of processes and analytics to mitigate this issue.
On a similar theme, panellists discussed the importance of CDMO selection and the need for companies to build strong relationships with their manufacturers. Given the nature of cell and gene therapies, manufacturing is a complex, multistage process. Appointment of a CDMO is therefore not just a transactional decision. Companies need to pay particular attention to governance and project management, identifying how teams will work together and how projects will be run. A close relationship with the manufacturer will be crucial when something goes wrong in manufacturing (which, as one panellist emphasised, will happen!).
Although the discussion did not touch on the legal remedies that companies may look to when there is a problem with manufacturing, it struck me as I was listening that termination (often viewed as the ultimate legal remedy) is usually not going to be a viable option for CGT companies. Particularly given the current capacity squeeze, a CGT company will likely struggle to find an alternative manufacturer without accepting significant delays to development timelines. Of course it’s important for CDMO agreements to include termination rights, but negotiation time may be better spent ensuring that the contract includes practical mechanisms for identifying and resolving issues early. For example, is there a governance structure in place that enables oversight and communication between the parties? Is there a clear escalation mechanism to help with early resolution of issues? Panellist Curran Simpson (Chief Operations and Technology Officer at Regenxbio) emphasised the value of engaging a CDMO who is willing to allow representatives from the company on the manufacturing floor when the first batch of a product is being produced (subject to certain conditions). In practice, building practical rights like this into the contract may be more valuable for a cell and gene therapy company than any termination right.
Despite the focus on challenges faced by cell and gene therapy companies, the event also had some positive messages. The industry has largely been able to withstand the operational challenges of the past couple of years caused by the pandemic and it’s clear that innovation in the sector is continuing at pace. The executive interviews gave a taste of just how much innovation there is in the field with companies working on multiple different types of therapies for different indications. It was also emphasised more than once how important it is not to view all cell and gene therapies as the same. For example, we heard about the merits of allogeneic versus autologous therapies; the differences between in vivo and ex vivo gene editing; the use of viral vector delivery systems versus lipid nanoparticles; and how innovation in delivery systems will enable gene therapy to be used in a variety of tissue types. The hope is that by continuing to innovate and overcome current challenges, cell and gene therapies will be developed use in conditions with even larger patient populations.
Discussions about innovation were also not limited to the scientific and technical aspects of cell and gene therapies. Mike Fraser of Novartis discussed the need for continuing engagement on the issue of pricing and reimbursement. He discussed some of the innovative pricing models Novartis has agreed with payers for its product Zolgensma (e.g. annuity models, deferred payments and outcomes based payments), this is something we have written about previously in the context of downstream licence agreements (https://www.bristows.com/news/cell-and-gene-therapies/). It was encouraging to hear that payers and regulators have been receptive to the need for new payment models for these products.
Overall, this was an enjoyable and very informative event. Not only did it highlight just how many challenges still need to be overcome in the cell and gene therapy space, but it also showed just how much innovation is underway to address these.
As the gene therapy revolution starts coming to fruition, new challenges are emerging