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The concept of modifying the human genome to treat or cure disease was once the stuff of science fiction. Today there are products on the market to do just that. This amazing leap has come with a hefty price tag. Currently marketed gene therapies hover around $500,000 or more per course of therapy and future agents may top $3 million to treat a single patient.

Providers and payers must ask themselves a two-pronged question about gene therapy: Who should be treated and when?

CAR-T agents such as including Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) reprogram the genes of cancer-fighting cells to combat diseases like leukemia. Luxturna (voretigene neparvovec-rzyl)‎ treats a congenital eye disorder that results in blindness. Other diseases that may have therapies available in the next few years include hemophilia, lysosomal storage disorders, and several neuromuscular diseases. And there are hundreds of gene therapies currently in the pipeline for other diseases.


Precision Value & Health, the umbrella organization of Precision for Value, recently surveyed 25 decision-makers from 20 health plans and five integrated delivery networks on their concerns about gene therapy. Their responses back the “who should be treated and when” concerns. When asked about their primary concern with gene therapy other than cost, 35% of the respondents said it was selecting the appropriate patient and 30% said it was the need for retreatment, with a commanding 72% of respondents wanting more information on the durability of response. Those surveyed showed nearly twice as much interest in economic models showing long-term value of a gene therapy versus short-term value.

In other words, health care decision-makers have their eyes set on the long game when it comes to gene therapy.


The traditional approach for payers, and sometimes for providers, is to start with the least-expensive treatments first and hold off using more expensive ones until later. But when it comes to gene therapy agents that may dramatically alter a patient’s disease for a lifetime of benefit, is that the wrong approach?

Vaccines are a good model for evaluating long-term value in health care. Administered as early in an individual’s life as possible, vaccines prevent disease for decades, or even a lifetime. The costs saved from cases of polio, chickenpox, measles, diphtheria, and the like that never occurred because of vaccines are probably beyond calculation. Administering these same vaccines to individuals in their 20s or 30s is still valuable but considerably less so, as many would have already experienced the diseases these vaccines were designed to prevent and racked up costs for them.

Viewing gene therapy in a similar light suggests similar benefits. Why should a patient who is a good candidate for gene therapy experience years of chronic therapy first when the disease could be prevented with an earlier gene therapy intervention?

For some genetic conditions, disease progression may be irreversible, meaning that early intervention is essential to long-term health and cost-effectiveness, avoiding more health care visits, more complications, and more chronic drug therapy compared to later intervention.

Creating tests to identify appropriate patients who could receive gene therapy as early as supported by the clinical data would result in value that accrues year over year, starting as early as possible, just as vaccines do.

Consider lysosomal storage disorders. These diverse conditions are often caused by the absence of key enzymes or their defective production. Gene mutation is commonly to blame. Gene therapies are in clinical studies for several lysosomal storage disorders, including Pompe disease and mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome. According to the 2017 Magellan Medical Pharmacy Trend report, an FDA-approved enzyme replacement therapy for MPS VI, Naglazyme (galsulfase), costs approximately $680,000 per patient per year.

Commercial insurers retain members for an average of three years. A gene therapy that completely eliminates the need for enzyme replacement for an individual with MPS VI could still provide a positive return on investment if the gene therapy cost no more than $2 million per treatment, assuming at least three years of effectiveness. This simple analysis, of course, doesn’t account for savings accrued from avoiding deterioration of the condition, which is common in these disorders.

From an early treatment perspective, an insurer could avoid paying $680,000 a year for enzyme replacement therapy, assuming the gene therapy continues to be effective. Covering gene therapy for a patient at age 4 (the minimum age for enrolling in clinical trials aimed at MPS VI) would avoid costs associated with enzyme therapy of approximately $9.5 million by the time the patient turned 18. If the gene therapy cost $2 million, the net benefit for the insurer would be at least $7.5 million.

In contrast, authorizing coverage at age 12 would avoid enzyme replacement therapy costs of only $4.1 million, which would be overwhelmed by the $5.4 million the payer would have spent on enzyme therapy for the patient between ages 4 and 12. Add in the $2 million cost of the gene therapy, and this later-start strategy would cost the payer $3.3 million compared to saving $7.5 million for starting gene therapy early.

The disparity in results between the two scenarios is substantial, though it’s important to keep in mind that this is a best case scenario: It assumes that the gene therapy is at least as effective as enzyme replacement therapy and that after gene therapy the individual does not need chronic therapy.

Research must answer critical questions about gene therapy before early adoption can be considered. It will be essential to first provide evidence of a gene therapy’s long-term durability. If its effect lasts a lifetime, early intervention is logical. But if it is effective for only five to 10 years, the value equation shifts and chronic therapy may be better in all but the cases in which it fails or is not tolerated. Gathering solid data about the effectiveness of gene therapies in young populations (under age 5) will be crucial. Just because a gene therapy is successful in an adult does not guarantee success in an infant or child.

One concern raised about early intervention with gene therapy is that the liver and other organs of young children are still developing. New liver cells would contain the patient’s original genes instead of those introduced by gene therapy. In theory, if a patient is treated at too early an age, the cells modified by gene therapy could be overwhelmed by native cells and reduce the therapy’s effectiveness.

Gene therapy is in an early phase. It is possible that we may never see it as broadly adopted in at-risk populations as we have seen with vaccines. Exposing an individual to a weakened infectious agent is one thing; modifying his or her genome is quite another.

Chronic therapies for genetic diseases may always play a role, particularly when data on gene therapy are weak or immature. For patients who are appropriate candidates for gene therapy, however, early intervention maximizes value by eliminating potential future costs.

As payers and providers come to grips with the gene therapy revolution, it may be worth thinking about adapting something learned long ago from vaccines: earlier intervention is better.

Jeremy Schafer is the senior vice president of the access experience team at Precision for Value, a company that provides services and infrastructure to support life sciences companies.