Making Cell and Gene Therapy Affordable

Cell and gene therapies (CGTs), which modify genes, gene expression or the biological properties of cells, have revolutionised medicine, providing personalised and targeted treatment for life-limiting diseases from genetic disorders to hard-to-treat cancers. Around twenty CGTs have been approved, and many more are in development. However, these cutting-edge therapeutics can come with a high price tag. [1]

Launched in the US in March 2024, Orchard Therapeutics’ Lenmeldy (atidarsagene autotemcel) is reported to be the most expensive drug in the world, with a price tag of $4.25 million. A one-time treatment, atidarsagene autotemcel is a gene therapy for metachromatic leukodystrophy (MLD), a fatal lysosomal disorder that leads to loss of sensation, cognition and motor skills. Infants usually die by five years of age, with patients with the juvenile and adult forms dying within 20 and 14 years of onset. Nine of the top ten most expensive drugs in the US are gene therapies, costing between $2.2 million and $4.25 million. [2, 3]

The cell and gene therapy market was worth around $18.12 billion in 2023, and is predicted to rise to $21.28 billion in 2024 and $117.46 billion in 2034, rising at an estimated compound annual growth rate (CAGR) of 18.6%. [4]

The high cost of cell and gene therapies has a number of drivers. Developing these types of therapies is high risk and complex, with years of clinical trials. The manufacturing process involves many steps, especially when the therapeutics are created for individual patients, there is only limited manufacturing capacity and only certain reagents are approved for use. The regulatory processes can be slow, especially as the technologies are new to the regulators. [1]

Looking at long-term costs

Many CGTs are ‘one and done’ treatments, and so the initial high cost needs to be balanced against a lifetime’s cost of drug and other treatments. Improving patients’ health also allows them to contribute to society through education and work, and through involvements in family and community life.

Using licensing agreements to control pricing

Licensing agreements, especially when assets arise from academic research supported by government funding, can be drafted to include clauses that keep prices lower for lower-income groups, and make sure that products are registered in lower-income countries to ensure access. The agreements could also be designed to ensure that exclusive licenses revert to non-exclusive licenses to stop companies shelving projects but retaining intellectual property.

Streamlining drug approval

Regulatory authorities can put in place programs that support CGT research, development and approval, for example the FDA’s Breakthrough Therapy Program and Regenerative Medicine Advanced Therapy designation.

The Breakthrough Therapy Program, which was implemented in 2012 and updated in 2018, was created to expedite the development and review of drugs for serious conditions that have potential to offer significant improvements over existing therapies. Companies developing a Breakthrough Therapy Program-designated drug can access: [5, 6]

· Fast Track designation – more frequent FDA meetings and written communications, and eligibility for Accelerated Approval and Priority Review and Rolling Review

· Guidance on drug development, starting from Phase I

The Regenerative Medicine Advanced Therapy (RMAT) designation, part of the 21st Century Cures Act, covers regenerative medicine therapy (cell therapy, therapeutic tissue engineering product, human cell and tissue product and certain gene therapies) developed to treat, modify, reverse or cure a serious or life-threatening condition. RMAT designated therapies gain the benefits of Fast Track and Breakthrough Therapy designation, as well as having the potential of accelerated approval. [6, 7]

Some CGTs are developed for ultra-rare disorders with existing treatments, where the patient numbers are so low that there is little chance of an economic return on the treatment. If regulators could allow continuous treatment under phase I-type cGMP (current good manufacturing practice) standards and clinical protocols, with informed consent, monitoring and adverse event reporting, patients would be able to access treatment, and researchers could collect data that would support further development of CGTs for other conditions. [1]

Overall, regulatory authorities need to keep up with the rapidly evolving science around CGTs and balance safety requirements with time-to-patient access. As an example, depending on national regulatory requirements, the scale up process from research to commercial-grade manufacturing can require comparability assessments, which can be costly. Using a risk-based comparability approach could reduce the regulatory burden, especially for academic institutions and small biotechs. [1, 8]

Reducing manufacturing costs

Cell and gene therapy manufacturing is costly and time consuming, driving up the eventual price of the therapy. Using open-source protocols created as part of collaborations between regulatory authorities, academia and industry and adopting standardised best practices, including equipment, methodologies and testing, could make a real difference to costs and speed to market. effort. [1, 8]

Autologous cell therapies require cells to be removed from a patient, manipulated and then returned to the patient. This can require the cells to be preserved and shipped long distances, increasing both the time taken and the costs incurred. Manufacturing at point-of-care (distributed manufacturing), rather in a centralised manufacturing plant allows cell therapies to be made at a clinic or local cGMP facility, reducing transport cost and complexity and potentially improving efficacy as the cells do not need to be stored as long. Closed automated manufacturing systems make point-of-care manufacturing more efficient as it reduces the need for clean rooms and highly trained staff, and lowers the chance of human error. [1, 9, 10]

Allogeneic cell therapies can reduce costs by up to 80 or 90% compared with autologous therapies by providing an off the shelf option. Cells are collected from a donor or pool of donors and engineered. However, the engineering required to reduce the risk of rejection can increase their risk, and their efficacy rates may not be as high. [10]

A partnership between Caring Cross, a non-profit organisation and Fiocruz, a biomedical research institution is working on an initiative to reduce the costs and access barriers associated with CGTs for people in Brazil. The plan will initially focus on CAR-T cell therapies for leukaemia and lymphoma and aims to optimise manufacturing processes and seek local regulatory approval in Brazil. Similar programs are under way in India and Europe. [11]

Using new technologies

New technologies can reduce the cost and the efficiency of delivery of genes into cells to create gene therapies. An example is the work carried out by ForCell based on technology from the University of York, UK. The new virus-free technology opens up cells through compression, without damaging or altering the cells, and has potential to be safer and lower cost than viral-based techniques. [12]

Changing pricing and business models

There are a number of approaches that could help ensure that more people can access CGTs. [13, 14]

· Annuity-based payments – payments are made in regular instalments, spreading the cost for the payer.

· Outcomes-based payments – a portion is paid upfront, and the rest paid if and when the patient reaches a pre-specified clinical endpoint, spreading the risk between manufacturer and payer.

· Outcomes-based rebates – a portion of the payment is refunded if the patient does not reach a pre-specified clinical endpoint, spreading the risk between manufacturer and payer.

· Outcomes-based annuity – payments are made in regular instalments, with a portion of the payment refunded if the patient does not reach a pre-specified clinical endpoint, spreading the cost for the payer and spreading the risk between manufacturer and payer.

· The ‘Netflix’ model – insurers/publicly funded healthcare providers pay a fee for access to unlimited numbers of treatments, spreading and reducing the cost for the payer and spreading the risk between manufacturer and payer.

While each of these models has its own challenges, including increased complexity to administer, and potential problems if patients transfer from one insurer to another, it’s vital that new pricing solutions, along with better regulatory and manufacturing approaches, are created to allow more patients to access life-changing treatments.

References

1. Kliegman, M., et al., A roadmap for affordable genetic medicines. Nature, 2024. 634(8033): p. 307-314.

2. Maragkou, I., The most expensive drugs in the US. Pharmaceutical Technology, 29 August 2024. Available from: https://www.pharmaceutical-technology.com/features/the-most-expensive-drugs-in-the-us/?cf-view.

3. Bansal, A., Lenmeldy becomes world’s most expensive drug. Pharmaceutical Technology, 2 April 2024. Available from: https://www.pharmaceutical-technology.com/analyst-comment/lenmeldy-becomes-worlds-most-expensive-drug/?cf-view.

4. Cell and Gene Therapy Market Size | Share and Trends 2024 to 2034. August 2024. Available from: https://www.precedenceresearch.com/cell-and-gene-therapy-market.

5. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. US Food & Drug Administration. Last accessed: 12 June 2023. Available from: https://fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy.

6. Haseltine, W.A., Bridging Gaps for Affordable Cell and Gene Therapies: Overcoming Financial and Systematic Obstacles. Inside Precision Medicine, 17 October 2023. Available from: https://www.insideprecisionmedicine.com/topics/precision-medicine/bridging-gaps-for-affordable-cell-and-gene-therapies-overcoming-financial-and-systematic-obstacles/.

7. Regenerative Medicine Advanced Therapy Designation. US Food & Drug Administration. Last accessed: 21 July 2023. Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation.

8. Khurana, M. and S. Singh. Creating A Scalable Cell And Gene Therapy Ecosystem. OliverWyman. Last accessed: 30 October 2024. Available from: https://www.oliverwyman.com/our-expertise/insights/2022/nov/health-innovation-journal/advancing-science-technology-for-everyone/creating-a-scalable-cell-and-gene-therapy-ecosystem.html.

9. Zynda, E., Affordable Decentralized Cell Therapies? Next-Gen Technologies Make It Possible. Technology Networks: Biopharma, 19 September 2023. Available from: https://www.technologynetworks.com/biopharma/articles/affordable-decentralized-cell-therapies-next-gen-technologies-make-it-possible-378982.

10. Sargent, A. The High Cost to Manufacture Cures. Charles River Laboratories. Last accessed: 28 February 2024. Available from: https://www.criver.com/eureka/high-cost-manufacture-cures.

11. A Unique Partnership Aiming to Make Cell and Gene Therapy Costs Affordable in Brazil. Last accessed: 30 April 2024. Available from: https://imapac.com/a-unique-partnership-aiming-to-make-cell-and-gene-therapy-costs-affordable-in-brazil/.

12. Martin, S., New technology could open up gene therapies to more patients at less cost. University of York. 11 July 2024. Available from: https://www.york.ac.uk/news-and-events/news/2024/research/new-technology-company-gene-therapies/.

13. Doxsen, K. Gene therapies could change millions of lives - so how will we pay for them? . World Economic Forum. Last accessed: 3 September 2021. Available from: https://www.weforum.org/agenda/2021/09/gene-therapies-rare-diseases-payment-affoardable-drugs-medicine/.

14. AuWerter, T., et al. Unlocking market access for gene therapies in the United States. McKinsey & Company. Last accessed: 22 August 2019. Available from: https://www.mckinsey.com/industries/life-sciences/our-insights/unlocking-market-access-for-gene-therapies-in-the-united-states.

About the Author:

Suzanne Elvidge

Based in the north of England, Suzanne Elvidge is a freelance medical writer with a 30-year experience in journalism, feature writing, publishing, communications and PR. She has written features and news for a range of publications, including BioPharma Dive, Pharmaceutical Journal, Nature Biotechnology, Nature BioPharma Dealmakers, Nature InsideView and other Nature publications, to name just a few. She has also written in-depth reports and ebooks on a range of industry and disease topics for FirstWord, PharmaSources, and FierceMarkets. Suzanne became a freelancer in 2006, and she writes about pharmaceuticals, consumer healthcare and medicine, and the healthcare, pharmaceutical and biotechnology industries, for industry, science, healthcare professional and patient audiences.