Karen Hodgkin, Chief Operating Officer (COO) of Cell Medica, spoke last month at the first Advanced Therapies Network (ATN) event about the challenges of setting up clinical trials for advanced therapies. Here she talks about the challenges faced in advanced therapies clinical trials, how the environment has changed since the CITADEL trial first started and the work that is being done to support this fast-growing sector.

Karen Hodgkin, Chief Operating Officer (COO) of Cell Medica, spoke last month at the first Advanced Therapies Network (ATN)  event about the challenges of setting up clinical trials for advanced therapies. Cell Medica is an SME that is committed to transforming the lives of patients with cancer by developing the therapeutic potential of off-the-shelf engineered CAR-NKT cell therapies. Their current focus endeavours to harness the natural biology of a specific subset of cytotoxic T cells, called Natural Killer T cells (NKT cells).

At the event, Karen presented an insightful and honest account of her experience running the CITADEL phase II multi-centre trial investigating the use of an autologous therapy (CMD-003) in patients with advanced extranodal NK/T cell lymphoma. Patients were recruited at 24 centres in five countries.

How has Cell Medica and your role changed since you first joined the company?

I started working for Cell Medica in early 2008 and was initially looking after their clinical development function.  As the Company expanded, regulatory affairs were added to my responsibilities and for last two and half years I’ve been COO so now overseeing a number of functions including manufacturing, quality, project management and HR.

When I joined, I was employee number five and initially we didn’t have an office so our meetings were in the founder’s dining room! Now we have sites in London, Houston and Zurich, and also have a clean room suite in the Cell & Gene Therapy Catapult’s Stevenage Manufacturing Centre.

What do you think are the biggest challenges for those conducting clinical trials on advanced therapies?

I think the challenges are often around getting the appropriate support. Most of those working in advanced therapies are SMEs and, finding the right external help is a challenge. As I described at the ATN event, we used a full-service Contract Research Organisation (CRO) to support us with the CITADEL trial. They provided the service but what we lost was the ability to interact directly with the clinical sites.

Logistics are always challenging; there are now are several service providers working in this space, for example specialist couriers and logistics management companies, but I still think it’s very difficult to move live samples around the world.

Can you talk me through some of the challenges that are more specific to the CITADEL study?

As I said at the ATN event, clinical trials always take longer than you think. In the case of CITADEL, we changed a critical reagent in the manufacturing process during the latter stages of process development. This was an important decision done on the basis of emerging data, but it did mean we had to go back a few steps.

In addition, the CITADEL trial was investigating an autologous product. It is often very difficult to get relevant patient material for process development and scale up activities; we have to rely on healthy donor material.  This can mean that when patient material is used, there are factors that may affect the quality of manufactured product, for example low blood counts or previous treatments.

At the ATN event you mentioned that it was important to talk to regulators early on – can you expand on this?

In my presentation I talked about the variation in length of time from submitting a regulatory package to getting clinical trial approvals in the various jurisdictions where we were working. When we had meetings with regulators the approval time was significantly reduced.

The Medicines and Healthcare products Regulatory Agency (MHRA) are promoting an open-door policy and the environment there is very collaborative and welcoming. You discuss areas that you think will be challenging, agree your approach and get their buy in at an early stage.

 

What is your experience of the different support organisations and resources available for advanced therapies clinical trials?

When Cell Medica started, the Cell & Gene Therapy Catapult wasn’t around and it was hard to find anyone with advanced therapies experience; the industry in the UK was quite embryonic. What the Catapult is now bringing is a concentration of expertise across different areas and they’ve been very important in lobbying and interacting with regulators. The fact that they have committed to the manufacturing centre in Stevenage for companies trying to build infrastructure is important.

I think the coordination role they are playing with Advanced Therapies Treatment Centres (ATTCs) is also key, because we have three consortia trying to tackle the issues for these disruptive technologies within the NHS; it’s vital that it’s all joined up.

Do you think there are any gaps in terms of support and resources in this area?

I think the UK government have identified advanced therapies as a key area, but we need to ensure these products are reimbursed. I think companies need to see that there is going to be a reasonable market opportunity for these types of products in the UK.

What is on the horizon for Cell Medica and the CITADEL trial?

The CITADEL trial finished last year and we’ve presented preliminary data at conferences and will be writing a full paper.

In Cell Medica, we have moved on to look at off the shelf therapies using allogeneic CAR products based on Natural Killer T (NKT) cells. The challenge of supplying an autologous product on a large scale is always going to be daunting and if we’re going to break into larger markets, we need a more scalable and straightforward off the shelf approach.

Karen Hodgkin presented at the ATN event on clinical trials at King’s College London on 13 February 2019.

The next ATN event on the 14 May will focus on investment.