War in the Blood: The battle takes shape in the burgeoning European oncology CAR-T market access space

With the continuing evolution of the CAR-T landscape, Research Partnership speaks to payers across Europe to investigate the market access and commercialisation potential for manufacturers of these exciting, in theory, one-shot personalised therapies.

I have a vivid memory of watching War in the Blood, a 2019 feature-length BBC documentary about CAR-T cell therapy and the potentially revolutionary impact on the landscape of cancer treatment. The filmmakers followed two leukaemia patients in first-in-human trials in the UK. CAR-T was showcased as their only hope and a way to re-programme the immune system to kill cancers. As with any clinical trial, questions arose. In this case, key questions centred around the long-term safety and effectiveness of the personalised CAR-T, due to its potential curative intent.

As more CAR-Ts have obtained marketing authorisation in the intervening years, similar questions have also been on the minds of payers and policymakers making decisions about how – and in which patient populations – to pay for this new modality, whose upfront cost and theoretically one-time administration is difficult to assess in the same way as traditional drugs.

In this article, Research Partnership reviews the market access opportunities and challenges encountered by CAR-Ts commercialised in the EU-4 and the UK (see Tables 1 and 2). To complement our review, we reached out to 12 payers in our network with advanced therapy expertise from across the UK, France, Germany, Spain, and Italy. We discuss their feedback and the ramifications below. We also share select findings from our new syndicated tool Access CGT, a cell and gene therapy analogue access and policy tracker.

Learning to live with a lack of comparators

In January 2023, Yescarta became the first CAR-T recommended for routine use for an aggressive lymphoma through the NHS in England. The NHS itself was the first European healthcare system to agree temporary reimbursement for CAR-T Kymriah a year prior to the BBC documentary. As part of a reassessment, the HTA body NICE further endorsed it after collecting real-world evidence (RWE) through the Cancer Drugs Fund and follow-up clinical trial data. This helped NICE overcome initial clinical data limitations, including a lack of comparative data that made cost-effectiveness analysis more challenging.

A lack of comparative data has also prevented the CAR-Ts available in Germany from securing a quantifiable additional benefit from the HTA body G-BA. The G-BA chairman, Josef Hecken, has previously called for controlled comparative studies for these advanced therapies before seeking approval, as not every evidence gap can be bridged with indirect comparisons or RWE collection – sentiments echoed by one of the payers in our network:

“Manufacturers should have comparative trials ready with appropriate endpoints at the time of launch/HTA assessment”.

German payer

Despite these challenges, the launch of CAR-Ts in Germany has been regarded as successful by a PwC study due to their uptake; as orphan drugs, their additional benefit has been considered proven up to the annual sales threshold of now €30 million, previously €50 million.

In Italy, HTA body AIFA granted Tecartus reimbursement and an innovative medicine status in mantle cell lymphoma in March 2022, with funding from the Innovative Medicine Fund. This was despite AIFA’s technical report criticising the lack of a control group, which limited the interpretation and generalisability of the results of the progression free survival/overall survival (OS) endpoints. Tecartus was also subject to a mandatory AIFA registry to resolve any uncertainty about its long-term effects.

Struggling to live with clinical and financial uncertainty

When asked about key challenges for future CAR-Ts in obtaining comparative evidence, the payers we spoke to strongly agreed on the difficulty in making pricing and reimbursement decisions based on innovative trial designs like single-arm trials (SATs). In fact, when questioned about how to ensure positive HTA evaluations for CAR-Ts, SATs were regarded as being a potential barrier, particularly among payers in France.

“Currently, it is necessary to have very solid real-world evidence, as well as clinical trial data with a comparator, in order not to obtain an ASMR V, which leads to no financial support [i.e., reimbursement].”

French payer

Notably, France’s Ministry of Health was questioned in the French Senate in April 2023 as to whether it intends to finance CAR-Ts Abecma and Carvykti for multiple myeloma. Both therapies received a rating of ASMR V (no improvement in actual benefit) from HTA body HAS, mainly due to the absence of a comparator arm. Once the corresponding decree is published, patients will no longer have access to these CAR-Ts via the paid early access scheme.

The lack of a comparator arm in a Phase II trial also led to Spain’s inter-ministerial pricing commission (CIPM) questioning the long-term response of Tecartus for mantle cell lymphoma. This clinical uncertainty, along with a high budget impact, resulted in a reimbursement denial in January 2022.

“For a CAR-T to be used in a significant number of patients, there is need to present statistically significant data of OS vs the standard of care and to improve safety.”

Spanish payer

Could allogeneic CAR-Ts impact the momentum of autologous CAR-Ts?

In December 2022, the European Medicines Agency (EMA) approved Ebvallo (tabelecleucel) – the world’s first nod for an off-the-shelf, allogeneic T-cell therapy (see Diagram 1). Ebvallo, marketed in Europe by Pierre Fabre, was approved for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder.

With production costs of an allogeneic therapy being lower compared to autologous CAR-T, most of the surveyed payers anticipate therapies such as Ebvallo to result in an easier reimbursement evaluation and to drive the overall price of CAR-T prices down.

“I hope this will have an impact and above all that the manufacturers will lower their prices [of CAR-Ts as a whole].”

French payer

However, one German payer did comment that Ebvallo may have limited impact, considering the small populations involved:

“The estimated number of patients eligible in Germany per year is four to max. 20 per year, which makes it an ultra-rare disease with limited influence on pricing.”

German payer

Even more than autologous CAR-T, allogeneic cell therapies are still in their infancy, with safety, efficacy, and durability largely remaining to be proven. However, there is a clear unmet need among patients in which autologous CAR-T is not a viable option for clinical and/or logistical reasons, and for a patient subset who relapse after autologous CAR-T.

Implications and outlook

The industry needs to continue highlighting the curative potential of CAR-Ts for a sizeable target population, despite European HTA bodies having made few adaptations to their value assessment frameworks to accommodate their specificities to date. Translating the curative intent into a demonstration of long-term societal cost-offsets is key to helping manufacturers argue for payers to consider a budget impact analysis that includes costs and savings beyond the drug or healthcare budget.

As some CAR-Ts are now already reimbursed, payers could become more demanding about the level of evidence package to include robust comparative data. Given the RWE value in helping to bridge the evidence gap, industry should continue advocating for a less fragmented collection of high-quality data across the EU to support decision-making.

While we wait to understand the impact of allogeneic therapies on autologous CAR-T pricing, it will be key to align on payment deals, like longer-term outcome-based models that reflect adequate value, to overcome payer challenges with their high upfront costs, without administrative burdens. This would facilitate timely patient access to CAR-Ts at a commercially viable price, allowing them to realise their potential to truly transform cancer care, as heralded in War in the Blood.

In this rapidly evolving cell therapy space, in which it is imperative for manufacturers to closely monitor developments across countries to understand how HTA body/payer sentiment is changing through policy and actual decision-making, Research Partnership has launched Access CGT, a syndicated analogue access and policy tracker incorporating payer feedback, to support our clients with this challenge. Find out more: researchpartnership.com/accesscgt

Tania R

Tania Rodrigues is an associate director in Research Partnership’s market access division. Tania manages qualitative global market access projects in varied therapeutic areas, with a particular interest in CGTs. Recent projects have ranged from understanding payer perceptions of the clinical value, HTA, and pricing potential of CGT product profiles, to providing guidance on key policy considerations to inform pricing and payment model decisions in the CGT space.

Research Partnership, an Inizio Advisory Company, is a world-leading custom and syndicated global insights partner for health and life sciences companies that optimises commercialisation success through evidence-based, story-told insights and recommendations. We provide custom market insights, syndicated real-world insights, and market access insights for the entire product lifecycle.

Derived through rigorous research design and socialised outputs and delivered through an agile, collaborative approach by market research experts and thought leaders, our insights empower better decisions and create long-term value for patients. Our specialist market access service supports the world’s leading manufacturers in market access, pricing, and reimbursement. To find out more please visit: researchpartnership.com/marketaccess

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