Car-t welcome to the jungle!

Written on Tuesday 3rd October 2017

Victoria Last, Consultant at OPEN Access Consulting (an OPEN Health company) has written an article on “CAR-T- Welcome to the Jungle”, regarding the forthcoming new, innovative CAR-T oncology therapies and the obstacles to patient access that they might face:

Oncology therapeutics are the rock stars of the pharmaceutical world. They are the game-changers, the innovators, and often the most publicised and emotive. The ongoing battle to beat cancer has propelled the advancement of oncology therapies with rapid speed since the discovery of chemotherapy some 80 years ago; with progression from the broad spectrum alkylating and platinum agents through to the more specific enzyme inhibitors, hormone antagonists and of course the advent of targeted immunotherapies using monoclonal antibodies.

However, as a previous cancer researcher, I have seen first-hand how Machiavellian cancer can be - where therapies work extremely well one month, only to fail the next. Or are very successful in one patient, only to have no effect in another. It is well known that cancers are multi-faceted and often there is no one-size-fits-all in regard to therapy. Which is why the approval of the world’s first autologous oncology therapy, personalised to the patient using their own T-cells is a truly revolutionary step forward – the latest front man in the band of oncology therapies, and is being cited as a ‘new frontier in medical innovation’ by regulators in the US.

With complete remission rates of 83% within 3 months of treatment in paediatric/young adult patients with relapsed or refractory ALL, the CAR-T therapy Kymriah (tisagenlecleucel) provides an additional treatment option for patients with the greatest unmet need. I first encountered CAR-T in my lab days some years ago when it was still in the testing stages, and I cannot say how thrilled I am to see the technology finally gain it’s first approval in the US. CAR-T technology will be sought after once it hits our shores; however, how easily will NHS patients be able to access these innovative gene therapies?

CAR-T technology requires a novel and complex patient pathway involving both manufacturing laboratories and patient clinics, in a process that takes around 22 days to complete. Therefore, the responsibility for the success of the therapy rests on numerous shoulders and will involve multiple NHS service touchpoints. Consequently, CAR-T faces the operational challenges of transporting and tracking blood and cryogenic products, alongside managing the potential expansion in patient numbers from the small numbers in clinical trials. However, as the product is cryopreserved this could give some flexibility to schedule the treatment at a time suitable for patients and the service.

In addition, patients receiving CAR-T therapies will be subject to close monitoring and staff will require specific training to ensure they can recognise and manage patients appropriately. As with many therapies that harness the immune system, CAR-T can potentially have serious and life-threatening side-effects, including neurological events and cytokine release syndrome (CRS) that can occur rapidly after infusion. CRS can be effectively treated using rescue therapies such as tocilizumab, however this also comes with a price tag. Furthermore, patients will need to be followed up over an extended period to evaluate long-term safety and efficacy.

NICE in 2016 explored the appraisal process of cell therapy products and concluded that the HTA methodology was applicable to CAR-T, therefore pathways need to be in place to ensure effective NICE implementation in the event of approval.  With numbers of cancer service managers reducing, and those that are left facing a higher patient throughput in a service that already struggles with capacity; the complex service pathway for CAR-T is a challenge, but also an opportunity to examine and redesign current patient pathways and promote efficient services.

Value-based decisions regarding CAR-T therapies will be dependent on cost. The production of the initial CAR and patient-specific end medicinal product is hugely expensive, and likely to result in a high cost product with a price tag of $475,000 (£367,391) being cited in the US. The additional costs including pre-infusion chemotherapy, potential CRS treatment and the multiple service touchpoints also need to considered. NICE cited that innovative payment methodologies need to be developed for CAR-T to manage risk and facilitate prompt patient access and have already begun discussions with producers on new ways of pricing expensive, one-time treatments such as CAR-T. It’s time to sing a different tune.

Additional filings for Kymriah are planned for later this year with further CAR-T products following closely behind, therefore appropriate planning for introduction of the paradigm-changing CAR-T therapies into the NHS is vital to ensure patient access. CAR-T – Welcome to the Jungle!

For further details about OPEN Access Consulting (an OPEN Health Company) please get in touch with Cathy Wright, Managing Director, OPEN Access Consulting at