As our ability to identify genetic markers of disease ushers in an era of regenerative medicine, it is also transforming another critical element of disease management: the clinical trial. While gene and cell therapy trials can be expensive, they are smaller in scale and more efficient than their traditional counterparts.
This could pave the way for a rethinking of the trial process more generally. Adrian Cottrell, chief information officer at the Institute of Cancer Research in London, argues change is needed, given that conventional trials involve thousands of patients and investigators around the world.
“That model is extremely expensive and makes up a huge proportion of pharma spend,” says Mr Cottrell, who spent 30 years at UK pharmaceuticals group GlaxoSmithKline.
Even so, gene and cell therapy trials are complex to conduct. “The process can take up to two months,” says David Hong, deputy chair of the Investigational Cancer Therapeutics department at MD Anderson Cancer Center, a research institution in Houston, Texas.
Cell therapy trials, for example, involve harvesting, re-engineering, selecting and growing cells before returning them to the patient, who must undergo lymphodepletion (chemotherapy that suppresses their immune system) before receiving the new cells.
There is also the question of who covers the costs. While trials are partly funded by drug companies, third-party payers (insurers or national health systems) can be responsible for covering complications incurred by patients. “So there’s all of this complexity, from logistical to financial,” says Dr Hong, who has led several cell therapy trials.
Unlike tests of drugs that, taken in the required dose, have predictable results, gene and cell therapies are living medicines that change specific elements in human DNA. This prompts a need for long-term testing.
“A conventional drug exists in the patient for a period of time and breaks down or is excreted,” explains Axel Hoos, head of oncology research and development at UK drugmaker GSK. “With cell therapy you only treat once and you have a living medicine that stays with you, so it’s important to know what happens to that over time.”
This also means the burden of risk must be spread, says Stanton Gerson, director of the Case Comprehensive Cancer Center and the National Center for Regenerative Medicine at Case Western Reserve University in Cleveland, Ohio. “You can’t put a risk on to the regulatory agency, the company and the product liability that says, ‘You owe me an outcome for the rest of my life,’” he says. “There needs to be a sense of shared liability.”
However, while traditional clinical trials involve large numbers of people — sick, healthy or both — as well as methodologies based on randomisation and testing for safety and efficacy, gene and cell therapy trials use only small groups of patients, all of whom have the condition the therapy is designed to address.
In the case of gene therapy, says Dr Gerson, its personalised nature makes it possible to determine efficacy based on tens rather than thousands of patients. “The approval process may accelerate dramatically in the next 18 months to three years because of its specialised, incredibly targeted utility,” he says.
This could also make it possible to omit some stages of traditional trials. “Some clinical programmes for cell and gene therapies can bypass the typical three-phase sequence and instead have a phase 1 study followed by a registrational study [designed to establish the benefit and safety levels needed to gain regulatory approval],” says Jeff Smith, a McKinsey consultant in Boston.
Another development with the potential to speed up gene and cell therapy trials is the agreement by the US Food and Drug Administration (FDA) to treat multiple groups of different processes as a single medicine for regulatory purposes, rather than demanding a new application for every adjustment.
“We call the original engineering process the parent cell therapy and when you make an adjustment to it, you call that the child,” explains Dr Hoos. “So you can continue your development process by adding a child, and another and a third and fourth, which accelerates cell therapy by years and keeps the trial small.”
The company is using the process with a cell therapy trial that aims to show clinical response in solid tumours while exploring its application in other cancer types. Dr Hoos, who describes the FDA decision as “very forward-looking”, says GSK is the first to use this parent-child approach.
Gene and cell therapy clinical trials also bring tests and cures closer together. “A lot of the trials are becoming the treatment,” says Dr Hong. “As to how we scale this, we’re not sure, but eventually people will figure out how to do it. It’s not going to happen next year but may happen in the next five to 10.”
What may also happen in that time is increasing personalisation of all sorts of treatments, as knowledge of human biochemical variation deepens. That, in turn, could lead to wider use of clinical trials on the cell therapy model, on a small scale and with a long follow-up.
While the long-term testing of gene and cell therapies places an additional burden on patients, new technologies such as mobile apps are making this far easier to manage than in the past.
“Because the technology and people’s readiness for the technology is in place, once you connect it with a problem, it’s easy to solve,” says Mr Cottrell. “And having solved it, the question is why aren’t we doing this for other trials?”