Above: Viral gene therapy. Image courtesy of Your Genome.

Nine months ago, the FDA made history by approving Casgevy and Lyfgenia, the first set of cell-based gene therapies to treat sickle cell disease (SCD). SCD is a debilitating genetic disorder caused by a mutation in the gene that encodes hemoglobin—the protein that enables red blood cells to transport oxygen throughout the body. Without functional hemoglobin, these cells form a “sickle” shape, which gives the disease its name. In the United States, nearly 100,000 individuals suffer from SCD, experiencing symptoms like anemia, chronic pain, swelling, and weakness, with a life expectancy as low as 52 years. Casgevy and Lyfgenia mark a significant advancement in the treatment of SCD. Traditionally, patients depended on blood transfusions and bone marrow transplants, both of which carry considerable risks and often do not completely cure the disease for many individuals. These innovative therapies provide a more focused, long-term approach to addressing the underlying issue of hemoglobin dysfunction.

Using Gene Therapy to Treat SCD and Other Diseases

Casgevy made headlines as the first FDA-approved therapy to use CRISPR technology in SCD treatment. By targeting, cutting, and deleting the gene that suppresses fetal hemoglobin production, Casgevy enables patients to produce fetal hemoglobin. Over time, the fetal hemoglobin replaces the dysfunctional sickle hemoglobin, restoring proper oxygenation throughout the body. On the other hand, Lyfgenia is a viral-based gene therapy that uses a lentivirus to deliver a functional copy of the hemoglobin gene to the patient’s stem cells, enabling the production of functional hemoglobin.

Above: Methods of engineering gene therapies. Image courtesy of StoryMD.

Beyond treatments for SCD, gene therapies come in three main varieties: somatic cell editing, STEM cell editing, and viral capsid delivery of edited genetic sequences. The first gene therapy to be approved in the United States was Kymriah, a somatic cell-based treatment for leukemia, which hit the market in 2017. In therapies like Kymriah, T-cells are harvested from patients and modified to insert a gene encoding chimeric antigen receptor (CAR) proteins. When reintroduced to the patient, the CAR proteins help T-cells locate specific markers on leukemia cells and kill the cancer.

Challenges with Gene Therapy

Each form of gene therapy presents its own challenges. For cell-based therapies like Casgevy, scientists must identify the specific mutation that causes the disease. However, for many diseases, the mutation is either unknown or multiple mutations require amendment. Viral-based therapies must identify the vector best suited for their product (such as lentivirus, AAV, or retrovirus) and genetically modify the virus to include the target sequence for delivery into the cell. Even if scientists can unravel these questions, sometimes the biggest problem is purifying and producing the therapy efficiently and economically.

Nonetheless, gene therapy’s potential to transform patient care has captured the attention of scientists and investors alike. Globally, nearly 500 gene therapy companies are optimizing this technology to cure cancers, heart diseases, autoimmune disorders, neurological diseases, and allergies. Even large pharmaceutical companies, such as Novartis and Bayer, that were initially hesitant about funding gene therapy research, have become more receptive as the field makes promising strides. 

This rapid increase in funding and development of gene therapy technology is driven by the desire to not just treat symptoms but cure the disease itself. Gene therapy is a powerful tool with which we can modify our genetic code and offer permanent, life-saving solutions to individuals and families with diseases that were previously deemed  “incurable.” However, with such power comes great responsibility for the companies developing these therapies. The FDA reviews gene therapy applications with unmatched scrutiny, requiring years of clinical trial success with infallible results, top-of-the-line purification, and optimized manufacturing, before approving a product. When a new gene therapy hits the market, it is a sign of years of clinical success under the watchful eye of regulators.

Pricing and Accessibility

As with all healthcare innovations, gene therapies come with a hefty price tag. Developing such complex treatments requires nearly a decade of research and investment before a new drug reaches the market. Investors expect a return on that investment, driving up the pricing of these therapies. For example, Casgevy is listed at a whopping $2.2 million per patient, which pales in comparison to Lyfgenia’s $3.1 million price tag. 

Gene therapy is just one example of a larger challenge of affordability in the healthcare industry. As technology advances, scientists will discover more advanced and personalized treatments that require expensive manufacturing. Per-patient prices of such drugs will have clear implications on product accessibility. The pricing of gene therapies, like other drugs, creates a difficult balance between ensuring healthcare remains accessible to patients with dire medical needs and incentivizing the investment necessary to drive the research and development of these life-saving therapies in the first place. Insurance and government officials inherit the task of reconciling these challenges, and their decisions and policies concerning gene therapy could undoubtedly revolutionize the healthcare industry.