Some of the hottest areas in biotech that are emerging and driving growth and investment are in the field of regenerative medicine and cell and gene therapy. There have been several acquisitions over the past year that really got the ball rolling with hopes to advance immunotherapies. Despite the curative potential, these therapies come with a hefty price tag and complex challenges. With the first immunotherapies to win regulatory approval in the United States, CCRM, a leader in developing and commercializing cell and gene therapies and regenerative medicine technologies, hosted a panel to discuss how we can bring these therapies to Canada.
The panel represented a wealth of knowledge covering regulatory and hands on approaches to the subject. It was moderated by Michael May, president and CEO of CCRM, and consisted of Donna Wall, MD, section head, Blood and Marrow Transplant/Cell Therapy Program, The Hospital for Sick Children (SickKids); Justin Shakespeare, executive director, Oncology Business Unit, Amgen; Patrick Bedford, senior manager, Clinical Translation and Regulatory Affairs, CCRM; and Aaron Dulgar-Tulloch, PhD, director of Bridge, GE Healthcare Cell Therapy.
There have been many decades of work in people trying variations of immunotherapy approaches and not getting a clinical signal. It was after researchers figured out T-cell biology and that they needed to bring not only the patients’ T-cells right up against the tumour cell but also that they had to get the T-cell excited and activated to go into cell division.
“The first successful patient was only about six years ago. No question that the treatment can cure, as long as you take six years as to how long to treat a number of patients who otherwise have untreatable leukemia,” says Wall. “That’s the first type of patients that we have when we have a new treatment. We take the patients where we have nothing else to offer. A number of patients do not make it to the treatment because it takes a while to engineer the cells; a number of patients may not have a response to the treatment; and a number of them who go into remission may end up relapsing. But for the first time, there are many who are responding positively to treatment and are not showing signs of leukemia.”
This is still in a very early-stage as of yet. It is not a one-and-done type of treatment. In order for this to work, the most common CAR-T product removes the cancer cells as well as the patient’s B-cells lifelong – giving them an immune deficiency. It is complex and comes with its own set of issues that may put up to 40 per cent of patients into intensive care for side effects of the CAR-T treatment. The treatment should not be taken lightly and will not be handed out over the counter.
The cost of the treatment is another factor entirely. Like anything new, cost is initially high but is expected to come down over time. It is a huge cost for a company to invest in and build the infrastructure that needs to be actualised as well as looking at regulatory costs. If the treatment becomes more mainstream, its costs pose another issue, as the health care system has not been designed to handle a large influx of big-ticket cases.
“There’s value in when you want to pay for something, but can you actually pay for it today is the real question,” says Bedford. “The number of drugs over $50,000 since a decade ago has gone from two to 20, and the drugs targeting orphan or rare diseases has all skyrocketed. There might not be a lot of people in each of these disease populations, but there are a lot of disease populations. So, the idea of affordability is really important. There are some new discussions right now about how to pay for these, like money back, or paying for performance type things, or rather than paying it all at once, pay three, four years later. There are a lot of ideas right now about how to afford the population if we choose they are worth the value to pay for.”
These are living drugs and therapeutics that have a very complex process on the manufacturing side as well as the rest of the supply chain. Each treatment batch is tailored to the patient. Many treatments start as autologous, but there are groups that are currently working on making this into more of an allogeneic process.
“Everyone wants to go from autologous to an allogeneic model. Every commercial entity would prefer to be in that allogeneic scenario because it is much better realised, there’s simplification in the supply chain, logistics, and the scale of benefits. We’re already starting to see groups trying to turn autologous into an allogeneic process,” says Dulgar-Tulloch. “I think we will see more groups coming in with successful approaches to a more allogeneic or classical model.”
However, the playing field is changing as more treatments are reaching approval on a shorter timeline and with less clinical data. Even though much of that data presented to the regulators have been enormously successful, it is not typically a fast-moving field. This leaves the regulators to navigate through the treatments and do so in a receptive and responsible manner.
Since these therapies are still so new right now, it has put a particular strain, even on a global scale, to find individuals with expertise in scale up and industrial manufacturing coupled with biological cellular experience.
“Canada in particular is feeling the pain from that, in that they don’t have a lot of the manufacturing infrastructure in Canada to pull from, and what we have is still heavily engaged in the bioprocess space, which they have been doing very successfully, and doing wonderful things for drugs and health overall as well,” says Dulgar-Tulloch. “It’s just a shortage of people and an opportunity that we need to address as we move forward and how we are going to train this next generation of therapy manufacturers.”
CCRM has a centre devoted to improving the cell manufacturing process and is attracting international attention from companies who are looking for CCRM and GE’s expertise in process development. This work also feeds into the Good Manufacturing Process (GMP) facility that CCRM is building that provides space for therapeutics companies to run phase I and II clinical trials.
What it all boils down to when it comes to markets like Canada, is that timing is often regulatory-driven and balancing considerations as to where manufacturing is and how to support the local market, with timing as an implication on the pricing perspective. Canada needs to leverage its strengths on the clinical side so that we extract value from manufacturing and ultimately deliver these products to patients for commercialization.