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  1. Learn About FDA Patient Engagement

How FDA is Putting the Patient Voice at the Forefront of Gene Therapy Clinical Trials for Hemophilia

By Najat Bouchkouj, MD, Bindu George, MD, and Karen Jackler, MPH

A person with hemophilia can experience aspects of their disease that even the most qualified doctors and scientists can’t fully appreciate. This is why the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA) is working to hear and understand the thoughts and concerns that people with hemophilia have about gene therapy as a treatment option and about participating in gene therapy clinical trials. Moreover, CBER strives to bring that information to the forefront of gene therapy development by sharing it with researchers, gene therapy developers, and other stakeholders, and by incorporating it into the work performed at CBER.

Hemophilia occurs because the gene that carries the instructions for making certain proteins, called clotting factors, does not work properly. Researchers are studying gene therapies for hemophilia to treat the disease by inserting a functional gene into a person’s cells so that the body can produce the clotting factors on its own. Developing a gene therapy for hemophilia is complicated, and gene therapy presents different risks than currently available therapies.

Before a drug or biologic can be made available to people in the United States, its safety and effectiveness must be demonstrated. CBER is the part of the FDA that reviews the safety and effectiveness of gene therapy products and information about how a gene therapy product is made.  As part of its mission, CBER also fosters the development of new and important gene therapies. For example, CBER convenes meetings to bring stakeholders together, such as the “Product Development in Hemophilia” workshop that was held at FDA on December 6, 2018.  The Center also develops public documents called “guidance,” such as the draft guidance issued In July 2018 called “Human Gene Therapy for Hemophilia.” which outlines CBER’s draft recommendations for gene therapy clinical trials for hemophilia.  Another way CBER fosters drug development is by bringing the patient voice into the gene therapy development process.

To bring the patient voice into gene therapy development for hemophilia, two CBER experts in adult and pediatric hematology led a listening session co-organized by FDA’s Patient Affairs Staff, the National Organization for Rare Disorders, the National Hemophilia Foundation and the Hemophilia Federation of America. People with hemophilia and caregivers of people with hemophilia were asked to participate in this rare disease listening session as part of a pilot program being conducted by FDA and NORD. The purpose of each listening session is to give FDA staff and disease communities the opportunity to engage and learn from each other on disease-specific issues. For this listening session, the CBER hematologists wanted to hear from people with hemophilia and caregivers about the factors they would consider if they had the opportunity to enroll in a gene therapy clinical trial.  During this session, CBER’s hematology experts heard*:

  • Consistent interest in understanding the benefits and risks associated with gene therapy and in receiving accurate and complete information about gene therapy and hemophilia.  All participants agreed that anyone interested in enrolling in a clinical trial, including children, should be able to understand the risks and benefits and be able to make an informed decision about enrolling. In addition to benefits and risks, participants described that factors affecting a person’s decision to enroll included how well the current treatment is working, the impact enrolling would have on the hemophilia patient and family, and the level of certainty around potential benefits.
  • Aspects of enrolling in clinical trials can be burdensome, but frequency of visits to the clinical trial site was not a top concern. Participants considered the success of the clinical trial a higher priority than the burden of multiple visits and tests when deciding to enroll in a gene therapy clinical trial. Even if the follow up involves an invasive procedure, like a liver biopsy or MRI, participants commented that once-a-year follow up is important for identifying and addressing the risks of a gene therapy as early as possible.
  • The definition of a successful gene therapy treatment varied. Some said they would consider a trial for a gene therapy successful if it could control symptoms for at least five years, while others would consider trials for therapies that could control symptoms for 10 or more years. Some would be satisfied with factor levels of five to 10 percent; others hoped for levels of 40 percent or more.

While this small group cannot represent the entire hemophilia community, it gave us the opportunity to hear and understand thoughts and concerns about participating in gene therapy clinical trials for hemophilia. This valuable input has already been used in ways that help advance overall development of gene therapy products for hemophilia. For example, FDA used input from the listening session to help shape the agenda for the “Product Development in Hemophilia” public workshop which was attended or watched on-line by more than 250 researchers, drug developers, FDA staff, and people with hemophilia and caregivers. Also, FDA’s Patient Affairs Staff made a summary of the listening session publicly available on its web site as a resource to help inform the design of clinical trials by taking into  account the needs and concerns of people with hemophilia. In addition, many of the themes that emerged during the listening session reinforced public comments received by FDA on the “Human Gene Therapy for Hemophilia” draft guidance.

CBER is grateful to the members of the hemophilia community for their willingness to participate in the pilot listening session and to share their views and experiences,­­­­ and to National Organization for Rare Disorders, the National Hemophilia Foundation, Hemophilia Federation of America and FDA’s Patient Affairs Staff for their efforts in organizing the listening session. The information from the listening session will enrich CBER’s efforts to foster the development of new and important gene therapies for hemophilia. Stakeholders now have a better understanding of how people with hemophilia and their caregivers, who are considering enrolling in a gene therapy clinical trial, weigh the benefits and risks, and what factors and outcomes they consider important. There is a lot to learn from the hemophilia community, and we welcome continued engagement and opportunities to bring ­­­­­­­their voices into gene therapy clinical trial development.

* With the knowledge of the call participants, other interested staff from FDA offices and NORD listened in on the call. 

This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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