Gene therapies and gene-edited cell therapies (CGTs) have undoubtably brought astonishing innovation and outcomes to patients with historically untreatable conditions, despite mainly gaining approval in rare, orphan indications. When the first CAR-T, Kymriah, was approved in 2017 it targeted the paediatric ALL population, with an estimated 400 new cases in the US per year. Likewise, the gene therapy Zolgensma was designed to treat the ultra-orphan indication of spinal muscular atrophy (SMA) with a 1-9 in 100,000 incidence. Due to the orphan nature of these indications and the exceptionally high cost of development and manufacturing, product prices have continued to set new records. With Kymriah having a list price of $475,000 and Zolgensma topping more than $2 million per patient, healthcare systems have struggled with high upfront costs, even within these small populations. Research shows that even within rare diseases, late-stage pipeline gene therapies are expected to cost up to $45 billion between 2020-2024. As therapies transition from small niche populations to larger patient populations (whether this be through expansion into earlier treatment lines or to diseases with high prevalence) the impact of how products can be priced, how reimbursement pathways are configured and ultimately how to achieve sustainable access comes into question.

From one to many, CGT treatment potential continues to expand exponentially

The number of emerging CGT biotechs grows by the day, as do their pipelines striving for increased novelty and therapeutic targeting potential. Innovative developments of CGTs have continued to expand at an exceptional rate, focusing on not just the expanding lines of therapy for rarer indications but in far more prevalent diseases, such as lung cancer and Alzheimer’s. There remains a clear unmet need due to a continued lack of truly effective treatment. With an estimated 6.2 million American’s living with Alzheimer’s, which is expected to grow to 13.8 million by 2060 and with 33% of patients with Alzheimer’s developing dementia within 5 years of diagnosis, the need for effective treatments continues. A research group from UC San Diego are aiming to administer Brain-Derived Neurotrophic Factor (DBNG) via an AAV-based vector-mediate gene therapy, having recently started a Ph 1 clinical trial. If successful, this could open up gene therapy to millions of people yearly. Yet, if they open up gene therapy to millions of Alzheimer’s patients, pricing will require a significant adjustment compared to Zolgensma’s hefty price tag.

But let’s not forget the impact of early line indication approvals for CAR-Ts, such as Yescarta and Breyanzi, CD19 CAR-Ts approved in DLBCL. Both have recently expanded their label from 3L to 2L DLBCL, with approvals expected for 1L DLBCL in the coming years. With each earlier line approval, the treatable patient population has the potential to more than double, enhanced by increasing HCP comfort of using such therapies. Historically unconsidered patients may now be referred for CAR-T over traditional treatments, such as ASCT; CAR-Ts alone are expected to address upwards of 2,000,000 patients by 2030. All in all, this increases the overall treatable patient population with these exceptionally effective, yet immensely expense, therapies. 

From small with big problems, to big with even bigger financial problems

With the sheer number of anticipated CGTs approvals, and the increasing competition against one another, each promising biotech strives to grasp a share of the healthcare ‘honey pot’. As the scale effect of transitioning from small niche population to treating larger patient populations, P&R strategies must account for global market-by-market access dynamics and economic realities. The current set up of healthcare systems just cannot sustainably provide infinite reimbursement of high upfront cost medicines. 

This is exacerbated by significant healthcare changes, such as the US pricing reform, expected to add further scrutiny to high-cost drug expenditure. To make healthcare more affordable and accessible innovative approaches from all parties are required. Ensuring CGTs are financially accessible and sustainable is imperative, as is continuing to demonstrate the transformative nature and potential long-term projected value to patients and payers. 

What sets CGTs aside is their potential to treat the root cause of a disease rather than just addressing the symptoms, with the potential of a cure from a single one-time dose. This therefore has the potential to create immense health equity and value, despite leading to exceptionally high up-front prices (costs of which payer systems around the world are not set up to support). Currently it is unclear whether the sheer volume of treatable patients will drive down the cost per patient (either from a patient numbers game or through COGM dispersion); a key question, as CGTs in part remain a personalized medicine. From paediatric ALL to solid tumours, and SMA to Alzheimer’s, prices need to either dramatically reduce or new innovative pricing methods must be established to balance wider access with sustainable healthcare spending.

Although outcome- or milestone-based payment models and value-based contracts continue to be adopted, the monitoring of such models also requires significant investment, infrastructure, and expertise. To manage cash flow and clinical responsibility of a seemingly infinitely expanding CGT patient pool, progress has thankfully driven cross-industry collaborations. The European Commission identified one of the key problems regarding P&R was the national ‘silos’ existing within the EU marketplace. EU fragmentation in this case has led to negative consequences to overall cost expenditure as a whole marketplace, as conventionally pharma would individually negotiate P&R and access with each target country. However, clear actionable steps have been made to address such challenges and streamline cross-market collaborations, such as the BeNeLuxA Initiative

What does this mean for pharma?

Whether emerging biotechs or established biopharma, achieving ROI for CGTs is a long game. With biotechs of all sizes demonstrating immense pipelines with a sharp eye on market entry and strong uptake, some boasting both gene-edited cell and gene therapies, it won’t be as simple as just securing funding. Whilst continuing to target hard-to-treat diseases, growing inter-indication competition and heightened global cost containment movements, a careful understanding of competitor pricing and consideration of market-specific affordability must be reflected within pricing strategies to enable not just successful access but potentially access at all.