Unblocking Access to a Pipeline of Gene Therapy Treatments

A genetic disorder is caused by a mutation in a single gene or multiple genes, or by a chromosomal abnormality. To date, more than 4000 genetic diseases have been linked to genetic mutations. These include cystic fibrosis, Duchenne muscular dystrophy, sickle cell anemia, hemophilia, Parkinson's disease and Alzheimer's disease. Some of these disorders can be treated with varying degrees of success, but none can currently be cured. Successful treatment with gene therapy, therefore, could potentially impact millions of lives.

Gene therapy has been a long time in the making, suffering a major setback following several patient deaths, including the highly publicized account of 18-year old Jessie Gelsinger, who died while participating in a clinical trial. In addition, gene therapy has been associated with very serious health risks, such as toxicity, inflammation, and cancer. These serious side effects were often traced to the use of viral vectors, which have long been used to deliver healthy genes to patients. However, contemporary gene therapy has become safer and more efficient. We’ve seen more stringent oversight by trial investigators and regulatory agencies; the application of innovative technologies; and in the case of viral-based therapy, new techniques to prevent the inherent viral mutation that may occur during manufacturing and render the vectors ineffective.

Limited Availability

Still considered largely experimental, most gene therapies are only available in a research setting, for example as part of the gene therapy programs that have sprung up in an increasing number of academic centers. But there are currently hundreds of clinical trials underway to evaluate gene therapy as a treatment for a variety of conditions. Slowly but surely, these products are entering the marketplace. The first gene product was approved in China in 2003 (Gendicine) to treat head and neck cancer. Gene therapy benefits could make an enormous impact in treating serious diseases that are otherwise untreatable except through supportive measures.

High Price Tags

While only a handful of gene therapies have been approved, many more are coming down the pipelines. But along with the promise of cures, these products come with unprecedented price tags. In 2017, Luxturna was approved to treat biallelic RPE65 mutation-associated retinal dystrophy, a rare congenital form of blindness. This was the first approved gene therapy to target a disease caused by mutations in a specific gene. The treatment was priced at $850,000, or $425,000 per eye. Zolgensma, which is used to treat spinal muscular atrophy, comes with a price tag of $2.125 million —the most expensive drug ever approved. A white paper issued by CVS Health looked at the impact of treatments for 11 diseases, projected to be launched within the next several years. Considering the potential population of patients who might be treated, and not knowing exactly how much the treatment will cost, the projected 5-year cost impact (2020-2024) would range from a low of nearly $15 billion to a high of $45 billion.

Making Gene Therapy Affordable

Drug manufacturers and payers are grappling with the challenge of how to provide affordable therapy, and solutions are being discussed and postulated. Novartis, the manufacturer of Zolgensma, has offered discounts to U.S. insurerson the condition they add Zolgensma to their coverage policies so that its use can be authorized quickly. Gene therapies, however, promise durable clinical benefit, and in the long run could substantially reduce costs associated with a specific disease. For example, Zolgensma is given only once, and its expense may be offset by the high cost of care normally incurred by a patient with spinal muscular atrophy.

Finally, there is also the uncertainty surrounding gene therapy. The long-term data don’t yet exist, so it is unknown if the benefits that have been observed are permanent. Even so, the research and innovation that help stack the pipelines aren't stopping anytime soon. These new therapies are here to stay, and there is an urgent need for new financing solutions and new reimbursement models that can ensure patient access as well as make gene therapy programs a more affordable therapy to patients.

SOURCES

Stolberg SG. The Biotech Death of Jesse Gelsinger. New York Times, November 28, 1999. https://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html

Keim B. Wired. Gene Therapy: Is Death an Acceptable Risk? Wired. August 30, 2007. https://www.wired.com/2007/08/gene-therapy-is-death-an-acceptable-risk/

Gene Therapy Net. Gene therapy products on the market. http://www.genetherapynet.com/gene-therapy-products-on-the- market.html

Novartis data suggest payers getting breaks on gene therapy Zolgensma. Reuters. October 22, 2019. https://www.reuters.com/article/us-novartis-zolgensma/novartis-data- suggest-payers-getting-breaks-on-gene-therapy-zolgensma- idUSKBN1X11SV

Gene Therapy: Keeping Costs from Negating Its Unprecedented Potential. CVS Health. https://payorsolutions.cvshealth.com/insights/gene-therapy-keeping-costs-from-negating-its-unprecedented-potential