In mid-February, leading oncologists received a letter from an international drugs company that appeared to confirm their worst fears about the impact of Brexit.
With the prospect of a no-deal looming, Kite, a subsidiary of the biotech giant Gilead Sciences, warned in the letter that it might have to cancel the UK part of a pioneering trial which aimed to prolong the lives of people suffering advanced blood cancer.
The trial, called Zuma 7, targets people suffering from relapsed/refractory diffuse large B-cell lymphoma, a common form of blood cancer. It was launched early last year as a global study involving hundreds of patients in 61 research locations around the world.
Zuma 7 involves CAR-T therapy, a state of the art technique under which cells are taken from patients and modified in the lab before being infused back into their bodies. In earlier trials, this has been proven to hold off the progress of cancer in advanced or otherwise hopeless cases.
This cellular engineering is at the cutting edge of anti-cancer science and demonstrates the complexity of supply chains in the pharmaceutical industry. With Brexit looming, this poses real problems for UK patients wanting to access world-class medicines.
Cancer cells taken from the patients were due to be harvested in the UK and exported to laboratories in the Netherlands for freezing, then shipped to Gilead’s facilities in California, before being returned to Europe for testing, then imported back into the UK where they would be given to patients.
At present, all the regulatory approvals to do this are in place, as the UK is part of the EU. The problem arose because genetically modified cells are considered medicines and, in the run up what looked likely to be a disorderly Brexit on March 30, needed approval to be imported from Europe. No-one knew, or knows what the new rules will be.
“The companies [looked set to decide that] that the risk of being unable to ship the cells back to the UK is too great and [were considering] calling off the UK arm of the study as a result,” said Prof John Gribben, a leading cancer specialist and head of the Centre for Haemeto-Oncology at Barts Hospital in London. “They didn’t want patients to be halfway through the treatment and then for us all to be stuck with not being able to get the cells back.”
It is understood that the MHRA, the UK regulatory authority, responded by writing to the UK industry as a whole, granting a six month grace period for companies involved in such cross-border trials. The previous rules would apply during that period, whatever the political outcomes.
Meanwhile approval from Dutch regulators was still required, and this took more time
Dozens more trials at risk
In the end, Kite received all the necessary assurances and wrote again to doctors in mid-March saying it would be proceeding with the trial after all.
The consequences of a decision not to proceed would have been extremely serious, for two reasons, scientists say. First, the patients are gravely ill and not responding to conventional treatments so are unlikely to survive until such time as the rules are clarified.
Second, there are dozens of trials involving genetic manipulation aimed at many different diseases. They are typically international in scope, with patients drawn from many different countries and drawing on the resources and expertise of biotech companies and clinicians around the world.
Despite the good news about Zuma 7, experts now fear that Brexit threatens the UK’s ability to participate in other cross-border cutting-edge trials.
“Collaboration plays an important role in cancer research, advancing scientific progress to help us understand disease and develop better treatments for cancer patients, comments Shaun Walsh, Head of Public Affairs and Campaigning at Cancer Research UK.
“Scientists from the UK and EU have a greater impact when working together – benefiting patients across the EU and beyond.”
Mr Walsh added that, whatever the outcome of Brexit, it was important to ensure that cancer scientists retained the ability to work across borders.
“The UK and EU should come to an agreement that supports researcher mobility and protects collaboration in cross-border clinical trials.”
Brexit is already having an impact on the flow of highly skilled experts into the UK.
Half of PhD students funded by Cancer Research and 76% of postdoctoral scientists at their institutes come from outside of the UK. There have been declining proportions of EU applicants at some of their institutes since the EU referendum result. In 2016, 28% of post-doc applicants at CRUK’s Glasgow-based Beatson Institute, a leading cancer research centre, were from the EU, falling to 13% of applicants in 2018.
In addition, some oncologists now report a growing shortage of key drugs, which may be the result of stockpiling pre-Brexit.”We are having to stockpile certain cancer drugs and indeed some clinical trials may not able to continue as we have not stockpiled the relevant drugs,” one said.
For more details on how Car-T works, follow this link to see an infographic : CAR T How it works_