8 things you should know about gene therapy

In 1972, 31 years before the Human Genome Project ended and a nearly complete sequence of the human genome was released, scientists proposed the idea of "gene therapy." These researchers saw the potential to treat genetic diseases by manipulating DNA but their enthusiasm surpassed the technological capabilities of their time. Fifty years later, gene therapy has not only come to fruition but is one of the fastest growing sectors in medicine. Here are eight things you should know about the present and future of the rapidly evolving field.

As of mid-2022, there were over 2,000 gene therapies in development worldwide, from early-stage research to late-stage clinical testing, double the number from just three years prior. This scientific explosion is translating into economic gains. The global gene therapy market is expected to increase from $5.33 billion in 2022 to $19.88 billion by 2027.

Sequencing the first human genome took over 13 years and roughly $3 billion. Today, sequencing the same amount of DNA takes mere days and can cost little more than $100. The ability to quickly and cheaply read DNA has been followed by new ways to edit DNA. Over the last 10 years, advancements in next-generation genetic engineering tools (e.g. CRISPR-Cas9, base editing, prime editing) paired with an ability to target cells across the body have improved gene therapy's safety, efficacy and feasibility.

The development of new tools is leading to the emergence of new companies. In 2021, 1,308 developers were working on gene therapy and related technologies, raising a record $22.7 billion, up 57% from two years prior.

With new tools comes a growing list of therapeutic targets. Clinical focus is spread across dozens of disease areas, including cancer, neurological, blood, immunological and cardiovascular diseases. These novel therapies are already changing lives. People living with sickle cell disease, cancers like leukaemia and lymphoma and multiple rare diseases have experienced remarkable improvements during clinical trials. Unlike traditional medicines that are taken over a person's lifetime and temporally alleviate symptoms, gene therapies are intended to be a one-time procedure offering long-term and potentially curative value.

In gene therapy, the patient is not just the recipient of a drug product; the patient is the product. The unique nature of these personalized treatments makes them difficult to regulate within traditional frameworks. In the United States, over 60 gene therapies are expected to receive approval by 2030, forcing the Food and Drug Administration to quickly evolve to adequately judge the safety and efficacy of these novel treatments.

These regulatory changes are creating ripple effects around the globe as countries seek to converge their regulatory requirements, making it easier and quicker for companies to bring their gene therapies to more markets sooner.

Once through regulatory approval, gene therapies have been entering healthcare markets with astronomical price tags. From $850,000 dollars to treat Leber congenital amaurosis, a rare eye disease that lead to blindness, to $2.8 million to treat beta thalassemia, a rare blood disorder, the trend for high prices is not likely to end soon. These price tags are down to high manufacturing costs, small patient populations, the need to recoup research and development investments and a range of healthcare market factors.

As a result, payers, providers and gene therapy companies are exploring novel payment and reimbursement models, some spreading costs over time and connecting amounts owed to patient outcomes.

While health systems are devising ways to deliver gene therapies to patients in the United States and European Union, most of the world is left waiting and wondering. In particular, low- and middle-income countries (LMICs) have very little access to gene therapies and carry nearly 90% of the global disease burden. While scientists appear to be on the verge of a gene therapy cure for sickle cell disease, roughly 90% of babies born with this disease are located in LMICs, areas which lack infrastructure for manufacturing and delivering gene therapy.

In August 2022, there were approximately 1,000 open gene therapy clinical trials globally, yet less than 5% were recruiting in LMICs (not including China), with only four trials in Africa.

The Bill and Melinda Gates Foundation is collaborating with Novartis, the United States National Institutes of Health (NIH) and other companies to develop single-shot gene therapy cures for HIV and sickle cell disease. The Global Gene Therapy Initiative (GGTI), an alliance of clinicians, scientists, advocates and community members, aims to launch gene therapy clinical trials in LMICs over the next few years, helping move these countries to the forefront of the global gene therapy conversation.

Like many other innovative healthcare technologies, certain scientific capabilities of DNA augmentation have begun to outpace effective legal and ethical oversight. To address this problem, in 2021, the World Health Organization released a governance framework for human genome editing. These recommendations provide guidance to countries seeking to realize the health potential of gene therapies while minimizing any nefarious uses of these technologies.

The last 50 years have witnessed gene therapies evolve from an idea to a global industry. These innovative treatments must now be developed and delivered in ways that benefit and are accessible to patients worldwide.