Guest Column | March 5, 2019

Designing Gene Therapy Trials For Access: What Payers & Health Systems Want To See

By Jeremy Schafer, Precision for Value


Gene therapy may be the next revolution in healthcare. The opportunity to cure diseases through the modification of the genome was once considered science fiction, but no longer. The United States has seen a few approvals in this area, including the approval of voretigene neparvovec for a rare form of blindness. In addition, CAR-T agents, two of which are available, have demonstrated alternative ways to treat disease by manipulating genes of different cells. The revolution does not come cheap, at least initially, with prices for these agents costing in the hundreds of thousands of dollars. Despite the cost, the promise of a one-and-done approach to debilitating diseases like hemophilia, blindness, and other genetic conditions is an attractive proposition. But what do those who will pay for these agents want to know?

At the annual meeting of the Academy of Managed Care Pharmacy, a presentation on gene therapy experiences in the U.S. and EU was shared. Results of a survey that included the perceptions of gene therapy among 20 health plans and five health system stakeholders were presented. When health plan respondents were asked their primary concern with gene therapy, 35 percent stated “selecting appropriate patients.” Another 30 percent felt the potential need for retreatment was the biggest concern. The notion that gene therapy would not go far enough and patients would still need conventional treatment for the condition was a top concern of 5 percent of respondents. These concerns fueled the top information needs for the health plan and health system stakeholders as well. A total of 88 percent of respondents felt information on appropriate patient selection as well as durability of response would be “very or extremely valuable.” Another 60 percent desired an economic model on the long-term value.1 Can clinical trial design help address these needs?

The challenges health plans face with gene therapy bear some similarities to the challenges of studying gene therapies in clinical trials. Clinical trials are designed to find a specific answer and get a drug to the next phase or onto the market as quickly as possible. However, gene therapies, even if their impact is immediate, rely on a value proposition that the patient may not need additional therapy ever again. To prove such an endpoint would take a literal lifetime. A CRO may find such an ongoing opportunity to be attractive, but a manufacturer is unlikely to pursue it. Gene therapy clinical trials should include a long-term follow-up plan to capture data on an ongoing basis. Checkpoints at regular intervals (every six months, annually, etc.) would provide crucial information to payers and providers on what can be expected after a patient receives gene therapy and whether a loss of response may occur and, if so, when. In addition, the ongoing data could be shared in publications, increasing the peer-reviewed literature footprint of the treatment. The long-term data would also serve a function in any economic models used with health plans. The longer the gene therapy’s effect lasted, the better the economic value, meaning each new data cut, if positive, would improve the financial model’s output.

Being able to identify appropriate patients for gene therapy will be crucial to product adoption by payers and health systems. The high up-front cost means delivering the medication to a patient who will not benefit is a substantial mistake. In fact, when surveyed on their approach to a patient who may be eligible for gene therapy while payer coverage is pending, three of the five health system respondents said the patient must wait until health plan approval before initiating therapy. Another respondent stated that while his institution will administer the therapy, it will do so only if the patient agrees to pay for the treatment if the payer does not. This indicates any uncertainty over whether a patient is appropriate for therapy can create significant access issues. 

Clinical trial designers can help mitigate the issue of patient identification by clearly defining inclusion and exclusion criteria for clinical trials, along with scientific rationale behind the choices. In addition, preplanned subgroup analyses will be valuable in determining appropriate patients. If certain subgroups do not respond as well to the gene therapy, or at all, this will help health systems and payers use gene therapy in the most cost-effective ways possible.

Stakeholders’ concerns regarding whether patients will need ongoing therapy with conventional drugs can be addressed by clinical trial design as well. Multiple genetic diseases treated with chronic drug therapy, such as hemophilia and enzyme deficiencies, are under investigation for gene therapy. A core question payers and providers have is whether the gene therapy will not only improve the patient’s health but also if chronic drug therapy can be ended. How this is answered, both in the short- and long-term, will be vital to the commercial opportunity for gene therapies. Clinical trial design can include outcomes to capture not only whether a chronic drug is still used but also how much is used. Given the cost of many rare disease therapies, a reduction in utilization of therapy could lead to a significant improvement in cost and quality of life for the patient. CROs should also track this information in any extension study to understand if a reduced (or eliminated) need for chronic therapy is durable.

Gene therapy is a treatment paradigm positioned for significant growth. But the unique nature of the space means stakeholders, including payers, health systems, providers, and CROs, need to adapt current practices. Being able to identify appropriate patients and provide data on a gene therapy’s long-term efficacy, safety, and impact on the use of medications for the disease will be crucial for product adoption. Adjustments in clinical trial design and execution to capture these data points may pay dividends upon product release and pave the way for more gene therapies to address some of the world’s most challenging genetic diseases.


  1. From Europe to the U.S.: The Challenge and Potential of Gene Therapies, Academy of Managed Care Pharmacy — 2018 Spring Meeting, April 24, 2018.

About The Author:

Jeremy Schafer, PharmD, MBA, is senior VP and director of the Access Experience Team at Precision for Value. He provides enterprise leadership across Precision’s Access Experience Team and leads integration with other enterprise teams including health economics outcomes research, provider marketing, access and analytics, and media outreach in the specialty space.  He has been involved in projects including payer value proposition development, ICER counter strategy marketing, market research in emerging areas like gene therapy and biosimilars, value assessment, and competitive simulations in oncology and specialty markets.