Chimeric antigen receptor (CAR) T-cell therapy is developing at a significant pace and excitement about its potential is high. CAR-T is set to revolutionise oncology and may also have the potential to treat autoimmune diseases as well as a range of other conditions. By engineering a patient鈥檚 own immune cells to fight tumours, the therapy opens the door to a new facet of personalised medicine.
So far, small clinical trials – primarily in patients with advanced blood cancers – have shown remarkable responses in both children and adults; when all other treatments had ceased to work.
However, major challenges lie ahead for the therapy. It鈥檚 debatable whether CAR-T can ever be truly effective against solid tumours such as breast cancer, and making the therapy safe and cost-effective 鈥� given its individualised approach 鈥� is a key issue in terms of insurance approval.
Products in the pipeline
In 2017, the US Food and Drug Administration (FDA) approved two new CAR-T treatments 鈥� Kite Pharma鈥檚 Yescarta (axicabtagene ciloleucel) for advanced lymphomas in adults, and Novartis鈥� Kymriah (tisagenlecleucel) for paediatric acute lymphoblastic leukaemia (ALL). More recently, the NHS has accepted Kymriah as a treatment for children with leukaemia in the UK.
Dr Helen Heslop, professor of medicine and paediatrics, and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas, USA, has a keen interest in CAR-T cell therapy and has seen its positive results first-hand at her clinic.
鈥淭he lymphoma product is available for adults with particular types of Non-Hodgkin鈥檚 lymphoma, and the other is licensed to treat acute leukaemia in young people up to the age of 26,鈥� she explains. 鈥淭he first one has been approved in the US for about a year and the second for eight months. In the pivotal trials they had very encouraging response rates.鈥�
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By GlobalDataAlongside these new products, Big Pharma is investing heavily in further research and development. With more than CAR-T therapy trials in the pipeline, we鈥檙e likely to see approvals for further indications over the coming year.
鈥淩esearch is happening in multiples directions,鈥� continues Dr Heslop. 鈥淭o improve the products, reduce the risk of relapse (by targeting other antigens), reduce side-effects, and extend efficacy to other tumours. To keep costs down it will also be crucial to develop a simpler, off-the-shelf product rather than having to make an individual product for each patient.鈥�
Price-tag problems
According to GlobalData analysts, Novartis鈥� Kymriah is expected to top $1bn in sales revenue by 2023 in the US alone. Estimates by other industry experts put the total cost of CAR-T therapy at up to $1.5m per patient.
In the US, the treatment鈥檚 price has been set according to indication and can total $475,000 per year. In Europe, the drug is likely to be priced in line with the $360,000 (拢282,000) that it has been listed for in the UK 鈥� an example of Europe鈥檚 more price-conscious approach to novel products. As it is covered by national health services, uptake of the drug should not be limited, he says.
However, the UK鈥檚 National Institute for Health and Care Excellence (NICE) is already researching value-based approaches to providing CAR-T and it may not be available to all if the figures don鈥檛 add up; the staggering cost of the therapy means it may not be viable moving forward if other existing treatments provide better value as first-line options across a broader patient base.
鈥淐osts are high at the moment which reflects the complexity of the product and also the original investment of the companies in doing the pivotal studies,鈥� explains Dr Heslop. 鈥淚t鈥檚 a product made from individual patients 鈥� they鈥檙e collecting blood, shipping it to a centre that does the cell processing and shipping back. It鈥檚 still a new paradigm and costs will stay high until next-generation products come on to the market.鈥�
The Holy Grail for the industry is the development of a multi-indication product that would require a less individualised approach.
鈥淎n off-the-shelf product would have the advantage of being available immediately and would of course be at a lower cost, which would make it more broadly applicable,鈥� continues Dr Heslop. 鈥淏ut, it鈥檚 probably quite a few years off before we have a product like that commercially available.鈥�
Costs are also likely to fall over time as a result of competition and optimisation of processing.
Approval issues and what lies next?
Insurance approval will continue to be lengthy process for CAR-T, particularly in the US, given high costs and the individualised nature of the treatment process. Safety issues have also been a factor in approval of the therapy, with serious side-effects posing significant risks to patients, which some clinicians say outweigh the potential benefits. Severe cytokine release syndrome has been the most commonly reported adverse reaction of CAR-T cell therapy in patients with blood cancers, and fatal cases of tumour lysis syndrome and other organ-specific toxicities have also been reported.
Initially, research in this area is expected to focus on other hematologic malignancies and on optimising the products currently available.
鈥淪olid tumours are more challenging,鈥� explains Dr Heslop. 鈥漈hey鈥檙e not such good targets for CAR-T, so that is going to take longer, but we鈥檒l get there.鈥�
She would like to like to see CAR-T products used earlier in the course of cancer so that patients don鈥檛 have to go through as much toxic chemotherapy: 鈥淭hen the incidence of late effects from these malignancies is less. An example would be paediatric ALL which has a very high cure rate, but the children have therapy for two to three years and this can have long-term side-effects.鈥�
She argues that if CAR-T cells were given earlier, so that long-term therapy was reduced, there would be multiple benefits and delayed side effects for these children.
鈥淐ell therapies can be very beneficial and certainly I have seen patients who are now long-term survivors after receiving these CAR-T therapies, so there鈥檚 a lot of potential,鈥� she concludes. 鈥淏ut, there is still a lot of work to be done to make them better, safer, cost-effective and more broadly available.鈥�
Cell & Gene Therapy Coverage on Pharmaceutical Technology supported by Cytiva.
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