What Do Patients Have to Say about Gene Therapy Trials? An Upcoming FDA Public Meeting to Hear from Patients and Caregivers

March 14, 2023By Larry J. Bauer, Senior Regulatory Drug Expert & James E. Valentine

Incorporating patient and caregiver experiences into every phase of drug development has become increasingly prioritized during both development and review (see, e.g., previous coverage here). Who better than people living with a condition to inform drug companies, physicians, academics, and the FDA on what it is like to live with their condition, what symptoms most impact their lives, what goes into their decision about whether to participate in a clinical trial, and what kind of treatment effects would be most meaningful to them?

The FDA took an early lead in the evolution of this movement when they launched the Patient Focused Drug Development (PFDD) initiative in 2012. Rather than speaking with one or two people with a condition of interest as had been previously done, they sought to find a more systematic way of getting broad patient and caregiver feedback. After holding a series of these meetings, FDA realized that PFDD meetings were extremely successful and wanted the process to continue. Knowing they could not hold PFDD meetings for every disease (there are over 10,000 rare diseases alone), they decided to turn PFDD meetings over to disease advocacy organizations, calling them Externally-Led Patient Focused Drug Development (EL-PFDD) meetings. The FDA continues to support these meetings through the Patient Focused Drug Development Staff and only infrequently takes the lead in organizing their own PFDD meetings.

To further expand patient input into product development, the FDA’s Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products or “OTP” (formerly the Office of Tissues and Advanced Therapies, or “OTAT”) is holding a free public workshop titled, Clinical Trials: The Patient Experience. The meeting will take place virtually on April 13, 2023, from 11:00 AM to 3:00 PM ET. This meeting will host a panel of rare disease patients, caregivers, and advocates to have a focused discussion on the emerging field of gene therapy (regulated at the FDA by OTP). At least some (if not all) of the panelists will have had experience participating in gene therapy trials. Topics of discussion will include:

  • The experience of finding and participating in gene therapy clinical trials as both a patient and a caregiver
  • The risks and benefits of participating in a gene therapy clinical trial
  • How the FDA works to ensure that gene therapy clinical trials are as safe as possible for patients

Gene therapy has the goal of trying to treat serious genetically based illnesses, which often are rare diseases caused by defective genes. The treatment consists of inserting healthy genes into an affected individual’s affected cells and tissues to try and stop or treat the disease. There have been challenges in gene therapy development. Early attempts at gene therapy had unseen issues.  In 1999, Jesse Gelsinger, age 18, died four days after doctors at the University of Pennsylvania administered a corrective gene encased in a deactivated adenovirus. Jesse was the first person known to have died in a clinical trial for a gene therapy.  This made many researchers take a step back and reconsider their approaches to gene therapy.  In the years since this incident, gene therapy technologies have evolved and R&D has taken off.

With this technology only relatively recently making its way into the clinic in a meaningful way, several other issues have been raised that warrant discussion with those who will participate in these studies and, ultimately, bear the benefits and risks of any licensed gene therapy:

  • Genetic testing and counseling (access to newborn screening, simplified genetic analysis)
  • Off target effects and potential side effects
  • Long-lasting effects of some therapies offering significant benefits but also long-acting permanent changes in the body
  • Opportunities for expanded access
  • Inclusion/exclusion criteria
  • Benefit/risk evaluation
  • Vector immunity
  • Limited accessibility of what are typically very small trials
  • Issues of equal access and discrimination

We have helped plan and moderate about 70% of the 75 EL-PFDD meetings that have been held to date and have heard many patient stories. We have heard first-hand from patients and caregivers about their experiences with gene therapies, as well as from others about their preferences and hopes for a potential gene therapy.

For example, at a recent EL-PFDD meeting for Metachromatic Leukodystrophy (MLD), caregivers shared stories of receiving an MLD diagnosis and then starting to look into possible gene therapy clinical trials. One family’s daughter was the first U.S. recipient in a gene therapy trial and seems to be doing very well. Other families have had to try and get access in Milan, Italy, where a gene therapy for MLD has already been approved. One family has two affected children, with one more advanced and in hospice care and the other thriving after receiving gene therapy in Italy:

It was an extremely emotional, difficult time for all of us. To see our younger daughter endure chemo treatments, lose her hair, not be able to eat (in preparation for gene therapy), and yet maintain her smile through it all – while the older daughter was getting worse with each passing day – was heart-wrenching…The gene therapy our younger daughter received in Italy transformed her life, and ours. Being able to see her not just survive, but thrive, brings me to tears. This is what our older daughter could have had if the disease was caught earlier.

Another family with two children with MLD had a similar experience:

I can tell you without a doubt that the gene therapy has helped our youngest son.  Now, he may not be “perfect”, but he is thriving and growing each day.  He does have some delays but has not regressed.  He is now the same age as my daughter (who is older and not eligible for gene therapy) was when she could no longer bear to stand up or walk as it caused her excruciating pain. While our son has weakness in his legs, and tightness in his left ankle, his latest nerve conductivity test revealed that it was stable when compared to the one performed when he was 6 months old.  This means that during the time that he should’ve been regressing and showing nerve damage, he was not!!  Instead, he is getting stronger, has started to stand up on his own, and is now walking with the assistance of orthotics, and a walker.

At an EL-PFDD meeting for people living with Wiskott-Aldrich syndrome, we heard:

(After receiving gene therapy) But gradually, we saw our son’s immune system start to work again.   Soon, he had platelets, and no longer was at risk of severe bleeding.  His eczema cleared up completely.  We were able to phase out the antibody infusions he was getting, and, best of all, we were allowed to start interacting with the world!   No more living in isolation! My experience with gene therapy transformed a parent’s worst nightmare – the threat to my child’s health – to the greatest gift I could ever receive – a new chance for a healthy life for him.

These direct experiences shared by caregivers provide insights into many of the issues relevant to CBER’s upcoming meeting: what burdens families will bear for the opportunity to participate in a trial; the types of benefits that are important to patients and families short of a complete cure; the likely inequities facing families unable to travel far distances; and the fact that many older, more progressed patients may not have the same opportunities to enroll due to inclusion/exclusion criteria.

Reflecting on our experiences with EL-PFDD meetings and other forms of patient engagement, the April 13th meeting, Clinical Trials: The Patient Experience, promises to continue the education of all of us on the patient experience with, and preferences for, gene therapies and their clinical trials.