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Navigating the gene therapy landscape

Posted on the 22nd February 2024

Gene Therapy Mai Blog

Mai Tailor, Regulatory Affairs Assistant at G&L, explores the multifaceted landscape of gene therapy and discusses the role of regulatory agencies, challenges in development, and the ethical implications associated with altering the human genome.

While shopping affords us a world of choice and possibilities, few would consider choosing the specific genes they would want their children to have.

Fueled by sensationalized media headlines, the misconception of gene therapy as a means of creating an “aesthetically perfect child” belittles its noble intentions of working to prevent fatal genetic diseases and address hereditary conditions where conventional treatments fall short.

Indeed, recent strides in genome editing technology have brought this precision medicine closer to reality (Brokowski et al, 2019).

The European Medicines Agency (EMA) defines Advanced Therapy Medicinal Products (ATMPs) as groundbreaking medicines based on tissues, cells, and genes, offering new opportunities to treat diseases and injuries.

Gene therapy, a subset of ATMPs, employs recombinant genes inserted into the host body to provide therapeutic, prophylactic, and/or diagnostic effects, targeting a wide range of genetic diseases (Brokowski et al, 2019).

Corrective gene therapy

Corrective gene therapy involves artificially engineered genes or bacterial nucleases to bring about desired alterations in the target genomic sequence (Alhakamy et al, 2021).

Despite the potential to cure genetic diseases, the journey toward establishing the safety and efficacy of gene therapy is arduous.

Concerns about misuse and unethical development necessitate rigorous regulatory processes, and technical challenges persist in developing gene therapy on a scale viable as an alternative to established treatments.

Additionally, there are multiple regulatory processes in place to allow Health Authorities to monitor, control, and foster new gene therapies while protecting patients.

In Europe, regulatory policies, such as Directive 2001/83/EC as amended (EMA, 2004) and Regulation 726/2004/EC (EMA, 2004), govern medicinal products for human use, including ATMPs.

Under EU law, clinical trials are mandatory to confirm safety and efficacy before regulatory approval is sought (Iglesias-Lopez et al, 2019).

The EU Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) play pivotal roles in product evaluation and approval (EMA, 2023).

In the United States, the Food and Drug Administration (FDA) oversees the regulation of human medicinal products, including advanced therapies such as gene editing.

The complex approval process involves an Investigational New Drug (IND) application for clinical trials, with final submissions to the Office of Tissues and Advanced Therapies (OTAT) within the Centre for Biologics Evaluation and Research (CBER) for marketing authorization (Iglesias-Lopez et al, 2019).

The fight for approval

Unsurprisingly, gaining approval for gene therapy is no simple task.

Bottlenecks in manufacturing processes, loosely established ethical frameworks, and the absence of harmonized policies pose challenges.

Companies face difficulties in developing therapies for rare diseases due to high costs with limited returns, complex regulatory guidelines, and issues with clinical trial site management (Drago et al, 2021).

Lack of harmonization across regulatory agencies complicates multi-country clinical trials, underscoring the need for international collaboration.

A further significant impediment to the manufacture of these treatments is the often-sizeable financial implications and low returns involved in developing small-batch gene therapy products for extremely rare diseases with a small patient population (Darrow, 2019).

Gene therapy manufacturing companies can also find it perplexing to deal with complex regulatory guidelines, access good manufacturing practice-grade reagents, and encounter problems with complex clinical trials (Drago et al, 2021).

Furthermore, the variation in the definition of gene therapy and its constituent elements across different countries adds complexity to reaching a consensus on regulations (Drago et al, 2021).

The innovative nature of ATMPs poses challenges for regulatory authorities in establishing a standardized assessment and control process. Nevertheless, international Health Authorities must surmount these challenges to advance the field of gene therapy.

That said, success stories are emerging.

For instance, Casgevy by Vertex Pharmaceuticals, a cell-based gene therapy, uses CRISPR/Cas9 technology to treat beta thalassemia and sickle cell disease.

It marks a significant step, being the first medicine using this technology to be recommended for conditional marketing authorization by the EMA (EMA, 2023).

The moral compass of gene therapy

The ethics of gene therapy, both as a concept and a treatment, are subjects of extensive debate.

Coller's 2019 article, "Ethics of Human Genome Editing," delves into various critical considerations. Religious leaders, with diverse perspectives on gene therapy, express numerous concerns about the procedures involved in modifying genes.

One method discussed in the article entails editing the genetic makeup of embryos before implantation, often resulting in the selective implantation of embryos into the mother's womb while others are discarded.

This practice contradicts the beliefs of religions that oppose research or artificial reproductive methods, fearing potential harm to or destruction of embryos.

Even among those who acknowledge the medical benefits of genetic manipulation, apprehensions arise when gene therapy is utilized for enhancing human performance.

The discomfort stems from concerns about disrupting the natural order and conflicting with religious beliefs, as individuals worry about potential adverse outcomes of gene therapy.

Additionally, there is uncertainty about whether the therapy will exclusively correct the targeted problematic gene without affecting other functions, a point highlighted in Coller's article.

Furthermore, modifications through gene therapy could potentially affect future generations of offspring, potentially manipulating entire populations if a particular trait were deemed desirable at a specific time.

While concerns about using gene therapy to halt the transmission of harmful genetic conditions can be mitigated, the same is not necessarily true for using it to enhance human performance.

Consequently, there is an urgent call for Health Authorities and professionals to develop ethical frameworks and regulations that include multigenerational consent for research methods capable of altering germline DNA (Coller, 2019).

Socioeconomic barriers to gene therapy

Unsurprisingly, the debate on the ethics of gene therapies also extends to their affordability, prompting discussions on whether it is ethical to develop treatments exclusively accessible to affluent states or individuals.

While certain gene therapies justify their high costs by serving as alternatives to complex treatments, reducing hospitalizations, and averting adverse medical side effects (Alhakamy et al, 2021), addressing this ethical dilemma necessitates collaboration among all stakeholders, including regulators and physicians.

Consider Luxturna (Voretigene neparvovec-rzl), a gene therapy designed for patients with a hereditary disease that causes vision loss due to mutations on both copies of a specific gene, leading to eventual blindness (Novartis, 2017).

Patients treated with Luxturna demonstrated a significant improvement in vision, and three-year follow-up data confirmed sustained results, affirming the treatment's safety (Darrow, 2019).

However, the substantial cost of Luxturna therapy, averaging 1,700,000 USD (Salzman et al, 2018), presents an obstacle for most patients.

Recognizing the impact of pharmacoeconomics on the accessibility of costly medicines, pharmaceutical companies like Novartis acknowledge this challenge and actively explore avenues to provide financial assistance to patients lacking the means to access these drugs in the United States (Novartis, 2017).

On a broader scale, global organizations such as the World Health Organization (WHO) are addressing the overarching challenges associated with the costs of novel medicines.

Recently, the WHO released a series of technical reports, emphasizing the urgent need for enhanced access to treatments in the European region (WHO, 2022).

The road ahead

Gene therapy holds immense potential and has witnessed unprecedented growth.

However, it will be some time before such treatments are commonly available.

In the meantime, regulators have a critical role to play as mediators among scientists, manufacturers, patients, and advocates.

While the biomedical field expands its capabilities, challenges persist. Striking a balance between scientific advancements and ethical considerations is crucial for the responsible development and deployment of gene therapies (Alhakamy, 2021).

Mai is a Regulatory Affairs Assistant based in G&L's Belfast office.


Alhakamy, N.A., Curiel, D.T. and Berkland, C. (2021) “The era of gene therapy: From preclinical development to clinical application,” Drug Discovery Today, 26(7), pp. 1602–1619. Available at:

Brokowski, C. and Adli, M. (2019) “CRISPR Ethics: moral considerations for applications of a powerful tool,” Journal of Molecular Biology, 431(1), pp. 88–101. Available at:

Coller, B.S. (2019) “Ethics of human Genome editing,” Annual Review of Medicine, 70(1), pp. 289–305. Available at:

Darrow, J.J. (2019) “Luxturna: FDA documents reveal the value of a costly gene therapy,” Drug Discovery Today, 24(4), pp. 949–954. Available at:

Directive 2004/27/EC of the European Parliament and the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use - Official Journal L – 136, 30/04/2004, p. 34 – 57

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European Medicines Agency (2023) Advanced therapy medicinal products: Overview - European Medicines Agency. Available at:

First gene editing therapy to treat beta thalassemia and severe sickle cell disease | European Medicines Agency. (2023, December 15).

Iglesias-Lopez, C. et al. (2019) “Regulatory framework for advanced therapy medicinal products in Europe and United States,” Frontiers in Pharmacology, 10. Available at:

Novartis (2017) “Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice.” Available at:

REGULATION (EC) No 726/2004 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL - laying down ►M7 Union◄ procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ L 136, 30.4.2004, p. 1)

Salzman, R. et al. (2018) “Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments,” Molecular Therapy, 26(12), pp. 2717–2726. Available at:

World Health Organization, 2022.

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