The double whammy of Brexit and the COVID-19 pandemic have posed major logistical challenges for the development of cell and gene therapies (CGTs) in the last two years. In spite of these obstacles, Europe’s CGT market is catching up to that of the U.S.
The CGT space experienced a shot in the arm in the last two years as the COVID-19 pandemic demonstrated the need for better therapies. In 2021, funding surged into companies developing CGTs worldwide. However, there were vast differences in investment growth between geographical regions; the majority of the growth took place in the U.S., with the European space seeing fewer investments than in 2020.
Experts met up to discuss the issues faced by European CGT players at the Advanced Therapies Europe meeting in London in September 2022. Chaired by Anthony Davies, CEO of the CGT specialist Dark Horse Consulting, the session placed a lot of emphasis on speed bumps slowing down the development of gene and cell therapies, caused by Brexit, the pandemic and the complexity of the European regulatory space.
Europe’s regulatory complexity
Unlike the U.S., the EU is a loose mosaic of independent member states. While the European Medicines Agency (EMA) assesses drug approval applications for the whole bloc, each member state has its own regulatory agency as well.
“When you hear the message: ‘this decision will be centralized and member states will take due consideration of the decision’, the bottom line is: they will still do whatever they want,” said Miguel Forte, CEO of Bone Therapeutics and president-elect of the International Society of Cellular Therapy.
This diversity in regulation also can be an advantage, as it allows lots of collaboration across the EU, and also with nations outside of the EU such as the U.K.
“What I appreciate about Europe, as complex as it is, is that we have easier access to the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and the French Agency for the Safety of Health Products (ANSM),” said Kinnari Patel, COO of the U.S. gene therapy developer Rocket Pharma. “I think some of the complexity is trying to marry it all together with the U.S. and trying to do it all in parallel.”
Brexit’s impact on cell therapy in Europe
Europe’s already complicated regulatory landscape became much more tricky for CGTs after the departure of the U.K. from the EU in 2020. The MHRA no longer follows the direction of the EMA when considering drug approval applications. However, this isn’t necessarily a bad thing.
“The MHRA impressed me greatly, especially in the early days of the pandemic, with the approvals of vaccines,” said Davies. Meanwhile, the EMA was slightly slower in approving the first generation of COVID vaccines as “the European landscape is much larger and comprises many more jurisdictions.”
According to Forte, having a bit of competition between the MHRA and EMA could improve the efficiency of the approval process down the road.
“I’m still very sad to see Brexit from a political point of view and a European point of view, but now that it lives on, let’s take advantage,” he noted. “I think the biggest challenge is that it takes time.”
The double whammy of Brexit and the COVID-19 pandemic proved a logistical headache for CGT development. This was especially the case for Rocket Pharma’s ex vivo gene therapies, where patient cells are extracted, genetically modified in the lab with a therapeutic gene, and returned to the patient. For example, many fresh products had to be shipped across the U.K.–EU border, and were stuck in customs checks while the patient waited in the hospital.
What often helped Rocket Pharma was that the MHRA worked hard to keep the trial going ahead.
“I appreciate the fact that the health authorities tend to run with us and help companies like ours, small biotech companies,” said Patel. “We need the collaboration to succeed as our patients can’t wait.”
With time, the panel expected things to get smoother with time as CGT companies and regulators gain experience in the post-Covid era.
“Controlling analytics and manufacturing makes it a little bit easier,” said Patel. “The more we know, the more we can get better at what we don’t know and how to solve all those equations.”
Inequalities in Europe’s cell therapy access
One aspect needing improvement in CGT development is the access of patients to life-saving therapies. In the U.S., for example, CAR-T therapies are only offered in a few specialized centers in the country, making it costly for patients living far away to receive the therapy.
“Europe is probably more homogeneous [than the U.S.], but is not yet at the level that it should be in terms of reach,” said Forte.
The EU has a strong regulatory body and is making efforts to streamline the path of new medicines to the market as part of its pharmaceutical strategy announced in 2020. One of the first steps taken was a harmonization of the assessment of medicines and health technology in late 2021. Under the new model, member states are expected to work together to help companies get new healthcare technologies through the approval process more quickly.
“Across Europe, I would like to see an evolution from a member state-based decision to pan-European, so that patients across Europe have access,” said Forte. Nevertheless, he added that member states still decide individually whether they are able to pay for new CGTs.
“We may be seeing some countries where it is easier for them to afford [the therapy], potentially giving easier access to the patient,” Forte added. “We’ll have to see how the market evolves.”
Europe’s cell and gene therapy scene catching up
In spite of many challenges to the development of CGTs in Europe, the continent has many perks from the U.S. point of view. This includes the scientific output and an availability of talent, which is in high demand in the U.S.
“There’s so many companies that the competition’s really high,” said Patel. “So we started getting a lot of the talent in Europe to come to the U.S.”
Europe’s cell and gene therapy space tends to be less aggressive and fluid than in the U.S., noted Forte, but Europe also has fewer academics with an entrepreneurial drive. However, he added that the trend is “improving in Europe and it’s catching up to the U.S. I’ve also started to see more aggressive investors in Europe that are willing to take risks and are scientifically knowledgeable.”
There’s also space for Europe to work with other CGT players in the rest of the world, such as the Asia-Pacific region. While many of the newest advanced therapies get their first approvals in the U.S. and Europe, Patel explained that patients all over Asia are in need of these therapies, and the U.K. has a framework allowing them to fly in and get treated. With time, potentially other countries in Europe in North America will make it easier for this to happen.
“At the end of the day we all follow the science and, in practical terms, we work together to impact patients’ lives,” said Patel.