Early and mid-stage clinical data on various immunotherapies have been extraordinarily promising, and while that is far from a guarantee of their eventual approval it is worthwhile for their developers to begin to think about the challenges ahead: large-scale production, regulation, pricing and reimbursement.
“The key challenge for this industry is to go from a single Michelin-star restaurant to a highly efficient chain of restaurants,” Kieran Murphy, president and CEO of GE Healthcare Life Sciences, tells EP Vantage. The company is working with hospitals, biotechs and big pharma to scale operations up so that cellular therapies are ready for the big time.
“We have no intention of ever marketing a therapy,” Mr Murphy says. Instead, GE Healthcare’s Life Sciences business provides bioprocessing expertise to pharma companies. It works with them to put in place standardised systems for cellular growth, purification and concentration that will be necessary to not only produce the therapies in sufficient quantity but also to show regulators that the production methods are rigorous and traceable.
GE is heavily engaged, he says, with companies including Novartis. The Swiss group’s CTL019 programme – genetically modified autologous T-cells designed to treat chronic lymphocytic leukaemia – will be the subject of a closely-watched presentation at the ASH meeting later this week (ASH preview – CART comes of age, December 1, 2014).
This project and others are at a crucial point in their clinical development, and though they are only in the middle stages now is the time to start thinking ahead.
If cellular projects continue to show themselves to be safe and highly effective they will need to be shepherded through a still-uncertain approval process.
“The regulatory path for many of these things is not clear,” says Mr Murphy. “We have a collaboration with the Karolinska [Institute] in Sweden where we are attempting to document the steps they’d have to go through for autologous therapy – effectively, what would a regulatory application look like?”
As well as the clinical results, Mr Murphy says, regulators will pay close attention to the methods of production of cellular therapies. Marrying flexible systems with data and analytics will give regulators confidence that the production system is robust, and that the manufacturing processes are traceable and can be monitored.
“We can help develop the software and analytical tools which are key for tracking therapy. The discipline in the supply chain is going to have to be rigorous,” he says.
With some of the early data on cell technologies being so impressive and the need so great, it has been suggested that it might be possible for some therapies to be approved on phase II data. If that does happen, it brings the regulatory and market stage that much closer.
And here the spectre of Dendreon haunts the sector. Developers of cellular therapies will have to act wisely if they are to avoid being on the wrong side of convenience (Lessons from Dendreon’s slow-motion car crash, November 10, 2014).
Mr Murphy says that GE’s Life Sciences unit intends to investigate the refining of the patient population, stratifying patients into likely responders for different therapies. This is done not only to please regulators but also with an eye on reimbursement.
T-cell and other cell-based treatments are going to be expensive, just as was Provenge, and it will be hard to bring the cost down despite the industrialisation of production processes that is GE Healthcare Life Sciences’ stock in trade. But Mr Murphy feels that the advantages of these approaches will justify their cost.
“Look at some of the monoclonal antibodies and the fact that people may have to stay on them for extended periods, not just for cancer but other diseases – these are not cheap. But for some cell therapies, a course of treatment is a cure,” he says.
If that does turn out to be how approved cell therapies are used, the pricing model could be similar to that of Gilead Sciences’ hepatitis C drug combination Harvoni: the high price is permissible as it is used for a short period and never again.
And it is worth considering the technology’s potential impact on chronic conditions beyond cancer, Mr Murphy says. “This is still in the fairytale stage of development, but if we can get to the point where, through cell therapy, we are able to get pancreatic cells to produce insulin, imagine the effect that would have on populations globally.”
The immunotherapies in development still have a way to go before they follow Dendreon’s Provenge to market, and it is to be hoped that they fare better than that ill-fated project when they do.
For that to happen the therapies will have to continue to generate impressive results in the clinic. After that, the companies will have to make some smart decisions when it comes to scale-up and pricing.