Alive and well

1 September 2020

Emerging stem cell and gene therapies provide unique challenges in a number of areas, including vendor selection and procurement. Emma Green speaks to Jacqueline Barry, chief clinical officer of the Cell and Gene Therapy Catapult, about the key considerations when conducting these trials, and the types of support that manufacturers can receive to ensure a smooth trial process.

Both driven by and driving the trend for more personalised treatments, cell and gene therapies are the latest revolution in pharma manufacturing. These unique living medicines offer promising patient outcomes, and can even be curative. They’re transforming treatment pathways and changing how sponsors need to think about clinical trials.

Although the market has expanded rapidly in the three years since the FDA first approved a gene therapy in the US, there remains, because of the novel and complex nature of these products, considerable uncertainty about how to conduct studies efficiently and effectively.

Still, with uncertainty comes opportunity. And, in those three years, the UK has seized that opportunity, emerging as a world leader for innovation in the cell and gene therapy field. At the centre of that success is the Cell and Gene Therapy (CGT) Catapult. Established as an independent non-profit in 2017 by Innovate UK, the CGT Catapult helps companies navigate some of the thorniest issues in developing and commercialising living medicines. It does so by providing access to expert technical capabilities and equipment while facilitating communication and collaboration between industry, academia, government, the NHS, industry associations and international organisations.

Innovate UK’s catapult model has been applied to developments as diverse as decarbonising energy supplies and launching satellites, but there are a number of factors that make living cell and gene pharmaceuticals particularly challenging for individual companies. “They’re much more fragile than a tablet, and their development is more complex,” says Jacqueline Barry, chief clinical officer at CGT Catapult. “You can’t simply run them through a mass spectrometer and know what’s in them.”

Moreover, the storage needs of cell and gene therapies are also significantly different than those of other pharmaceuticals. “If they’re not able to be cryopreserved – which more and more companies are trying to do – they can have a really short shelf life,” says Barry.

The autologous nature of these products adds another layer of complexity. “Usually, a part of the source is from the patient’s bone cells and tissues,” Barry continues. “There’s also the difficulty of the shelf life of the starting material going into the process. So, you’ve got both the after and antecedent supply chain, as well as the other challenges.”

That means cell and gene therapies also place extra demands on healthcare facilities. “You have an additional burden on the healthcare service because the patients have to go and then donate the cells for the therapy,” explains Barry. “They’re already quite busy with stem cell transplants for those undergoing bone marrow transplants, such as people who have leukaemia.

“They have to find additional slots and communicate with the manufacturer, and the manufacturer has to find a slot to make the products. The product then has to be transported back to the hospital for administration. All of that usually takes place over three to six weeks.”

With all those communicative and logistical hurdles, it’s not surprising that the CGT Catapult’s dedication to collaborative problem-solving has helped make the UK a popular location for cell and gene therapy clinical trials. The 127 ongoing trials in the organisation’s 2019 UK advanced therapies medicinal products (ATMPs) clinical trials database represent about a 45% increase compared with 2018, and account for 12% of global cell and gene therapy clinical studies.

“It’s quite a big thing to do, because a vast majority of the people that so need these products are in the US,” says Barry. “The UK actually really punches well above its weight in terms of the number of products that are developed in the country, especially at London hospitals. You’ve got the US, you’ve got Asia, and then the UK is actually the third cluster for the development of these products – which is quite astonishing given our size.”

As Barry sees it, that has a lot to do with how willing UK industry has been to join CGT Catapult in promoting and accelerating cell and gene therapy trials. “The capital and the support that manufacturers get to begin to help them with their process development is a big help,” she says. “And we see that both UK academics and companies provide support to companies coming into the UK. So we are sort of a soft landing for them.”

The MHRA’s interest in supporting innovation acts as a further catalyst. “They’re such a good, pragmatic, progressive regulator,” says Barry. “In terms of approving clinical trials, there’s a 180-day approval timeline for ATMP material. So the MHRA also tries to approve them in a timely manner. All of those factors added together makes the UK a great environment to do trials.”

Ballistic capability

The coordination and expertise provided by CGT Catapult is another key factor in enabling this productivity. “We’re coordinating a national network of advanced therapy treatment centres in Scotland, Wales – unfortunately not in Northern Ireland yet – and England,” says Barry. “This started just over a year and a half ago.”

Receiving this dedicated help and guidance can be hugely beneficial in improving efficiency. “We help companies with the process development and analytical development,” explains Barry. “This enables them to move along to manufacturing the products more quickly.”

The cell and gene therapy-specific expertise is particularly valuable. “Within my team, I have experts in regulatory, non-clinical and clinical development,” says Barry. “The experts are of different disciplines but all specialise in cell and gene therapy, which is quite unusual.”

In such a new and fast-moving field, it’s also vital. It’s rarely possible to apply traditional models to cell and gene therapies, so access to the CGT Catapult’s talent is a real selling point for the UK. “As you can imagine, doing non-clinical studies on a human-derived product is entirely different because if you put a human cell into an animal model, it’s going to be seen as foreign and it’s going to be eliminated,” explains Barry. “The understanding that there are unique approaches to that is really helpful, because sometimes animal models might not be appropriate, or there are particular types of animal models that are required.”

And when it comes to scaling up and commercialising an ATMP, economic models are as important as animal ones. The CGT Catapult also employs experts in health economics and market access. “The clinical trial group and health economics group work together to come up with a target product profile that is appropriate for the regulatory pathway, but also, ultimately, for the reimbursement pathway,” explains Barry. “We’ve got experts in IT, so they can help developers learn how to protect their IP and clinical trials. So we help them in a kind of multifaceted way.”

Within cell and gene therapy clinical trials, there are particular disease areas where the most work is being conducted. “Globally, there’s just over a thousand trials on advanced therapy medicinal products, and the large majority of those are in the oncology space, especially the immuno-oncology space,” explains Barry. “There are now a number of licensed products that have actually received MHRA approval.”

Ophthalmology is also quite a popular area. “It’s easily accessible, and there’s an acute and unmet need,” says Barry. “If you’re using a discrete amount of cells in quite an immune-privileged site like the eye, you can use fewer cells. And so, there’s quite a lot of gene therapies that are looking at inherited genetic disorders in this area.”

In light of the considerable interest in these therapies, it’s likely the sector will continue its rapid growth. “What we’re currently seeing is more and more trials moving to more mature clinical trial stages,” says Barry. “It used to be all phase-I and II, but now there are more in phase-II and III.”

No cell out

Of course, this isn’t the case for all types of studies. “Those that are focused on genetic disorders don’t follow the classic three phases,” says Barry. “Quite often you only treat 12 people globally, and then you go through a marketing authorisation. When you’re seeing such remarkable results, then the products aren’t following the standard clinical trial pathway.”

Sponsorship of trials is also shifting. “The more mature trials are moving away from academics producing and running them to industry sponsors,” explains Barry. “I suppose it’s just reflecting the tradition of the field. Ten years ago, it was predominantly academics that were producing these products, whereas, as the area has progressed significantly, now there are more and more commercially sponsored trials.”

The UK in particular is likely to witness rapid development because of the supportive environment. “The Advanced Therapy Treatment Centres [ATTC] network is helping the NHS be ready for these therapies,” explains Barry. “A national alignment for health programmes is going to be rolled out, [and] we’ve got a knowledge-sharing platform, and we’re helping to establish a group to help pharmacists get used to dealing with these products. So what we’re really doing is upscaling the pharmacy environment.”

This groundwork will help ensure that products can be much more quickly integrated into the NHS and, subsequently, other healthcare systems worldwide. “The fact that NHS England are involved, and they’re looking ahead, makes the UK a very attractive place for the world to come and do trials and launch the products,” says Barry. “They’ve got quite a costly price tag, but if you set that aside, it might be a one-off treatment that will cure somebody from a very early age. It’s quite a difficult thing for healthcare services to deal with, but because NHS England and NICE are very engaged with these products, they understand and they’re spending a lot of time planning for them. It’s a very advantageous space for developers.”


The proportion of global cell and gene therapy clinical studies taking place in the UK.


Ongoing ATMP CGT Catapult trials in the UK in 2019.
CGT Catapult

Case study: clinical trial of an immuno-oncology treatment with UK universities

A novel approach to the treatment of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) was being developed by scientists at Imperial College and University College London (UCL), initially funded by the charity Leukaemia & Lymphoma Research. Patients with these diseases often have limited treatment options and a poor prognosis, meaning new treatments are much-needed. A new multiparty approach was needed in order to accelerate the development, through clinical trials of a treatment, of a T-cell therapy that targets the overexpression of the WT1 antigen.

Working in collaboration to find a solution

CGT Catapult, UCL Business and Imperial Innovations worked together to form a new joint venture company, Catapult Therapy TCR, to manage the development of the WT1 cell therapy. Having a spin-out also allows everyone to share in its eventual success.

Outcomes so far

CGT Catapult was transferred the sponsorship of the existing UK trial, which is focused on AML. It has opened new sites and accelerated recruitment. Successful interim safety results were achieved in this trial in early 2016. In addition, it set up a new trial targeting MDS, with sites both in the UK and selected other European countries. This both demonstrated and expanded the experience and expertise of the regulatory and clinical operations teams, as the trial progressed through the approval process for Gene Modified Organisms and Clinical Trial Application, and clinical trial setup in the UK, Belgium, Germany and France.
Source: CGT Catapult

There is lots of support for cell and gene therapy research in the UK, enough to propel the country to one of the most important locations in the world.

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