Gene therapy: a radical pharmaceutical revolution

Gene therapy is an innovative, fast-evolving modality offering revolutionary capability in multiple disease areas. According to research by 360iresearch, the global cell & gene therapy market is estimated to value $135.04 billion by 2030.

In this Q&A, Karen Pinachyan, Head of Medical Affairs Europe at CSL Behring summarises key considerations for gene therapy drug development and the ideal approach for alleviating economic strain when advancing these modern treatments.

How has the gene therapy landscape evolved over the last several years?

The clinical application of gene therapy has been investigated for decades, with the first clinical trial of such a treatment for a rare inherited form of immunodeficiency taking place in the US in 1990.¹ It took another 22 years for the first drug to be approved in North America or Europe, when the European Medicines Agency (EMA) granted conditional approval for an adeno-associated virus (AAV) drug indicated for the treatment of a rare lipid disorder, lipoprotein lipase deficiency.²

Since then, the pace of research and development has increased considerably, to the point where there are now more than 2,500 active clinical trials taking place.³ Gene therapies have evolved and new approaches have led to greater precision in making changes in the genome. For example, AAV based gene therapy delivers the functional gene in a single dose to treat genetic disorders.

Considerable progress has been made in other areas including enhancing safety, improving treatment administration and patient monitoring systems and implementing innovative pricing strategies – all with the goal of providing timely access to eligible patients who can benefit from these treatments.

What is the main reason economic uncertainties are impacting the gene therapy sector? How could this be mitigated?

As gene therapies are highly innovative, with many new treatments being the first of their kind, substantial investments are required across multiple stages, including extensive research, clinical trials and specialised manufacturing processes. Economic uncertainties can therefore lie in the high cost involved in drug development, manufacturing and delivery.

The impact of a one-time gene therapy treatment on national health budgets must also be considered, particularly at a time when many healthcare systems are facing financial challenges. Mitigating these economic concerns requires a multi-faceted approach, including appropriate models to assess and account for the projected long-term durability and potential cost savings for gene therapies. Fair and value-based pricing models, collaborative partnerships, and investment incentives can help align the cost of gene therapies with their clinical, societal and economic benefits.

What is the biggest impact gene therapy is having on clinical trials?

As more investigational gene therapies reach the clinical trial stage, including those focused on rare genetic diseases that were previously considered too challenging to treat, we are seeing the emergence of novel trial designs.

Particularly, haemophilia is often seen as a case study for gene therapy in the rare disease space. This modality has the potential to provide these patients with freedom from bleeds and the burden of lifelong treatment.

EC approves first gene therapy for haemophilia B

As more investigational gene therapies reach clinical trials, including those focused on rare genetic diseases that were previously considered too challenging to treat, we are seeing the emergence of novel trial designs.

The small numbers of people diagnosed with rare genetic diseases, as well as the overall health of the patients means that we have had to rethink the trial process from end to end.

But it is not only the pre-approval trials that have seen changes – this therapy has also shifted the wider relationship between industry, patients and health care professionals. For example, market access authorisation comes with a requirement to monitor patients for much longer than traditional medicines. In Europe, the EMA requires up to a 15-year follow up of patients. The US Food and Drug Administration (FDA) requires a patient follow up period of at least 10-15 years.^4,5

What is the key consideration drug developers should apply to gene therapies?

Gene therapies have the potential to transform the lives of people with genetic diseases. However, essential considerations for gene therapies include early drug development and evidence planning. For example, this involves identification of the patient population, disease subtypes, competitor analysis, and evidence of an unmet need.

Developing a novel therapy can be very expensive due to the complexities of and investment required in R&D, as well as manufacturing costs. This is amplified by the fact that gene therapies are often developed to treat rare diseases, so the number of patients to be treated is limited. Pharmaceutical companies need to work closely with governments and health authorities to find innovative contracting and payment models, such as outcome-based agreements, which consider the clinical and economic value of the treatment to patients, healthcare systems and society.

It is also important for pharmaceutical companies to work closely with specialists and clinical treatment centres to ensure they are prepared to identify eligible patients, administer gene therapies and monitor patients in the long-term. This close collaboration is vital to ensuring the future delivery of care.

References

1. Blaese RM, Culver KW, Miller AD, et al. Science. 1995; 270(5235): 475-480.
2. [Internet] European Medicines Agency. 2017. [cited 2023August]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/glybera.
3. Anguela XM, High KA. Annu Rev Med. 2019; 70:273–288.
4. Guideline on safety and efficacy follow-up and risk management of Advanced Therapy Medicinal Products.
   [Internet] European Medicines Agency. 2018. [cited 2023August]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-safety-efficacy-follow-risk-management-advanced-therapy-medicinal-products-revision_en.pdf.url.com.
5. Long Term Follow-Up After Administration of Human Gene Therapy Product. [Internet] FDA. 2020. [cited 2023August]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/long-term-follow-after-administration-human-gene-therapy-products.