Gene Therapy Clinical Trials: The Patient Experience

This blog was authored by the Medidata Patient Insights Board.

The best way to stay up to date with key issues facing patient populations in a given disease state is to attend a Food and Drug Administration (FDA) listening session. The Patient Insights team at Medidata regularly attends these sessions to make sure the patient perspective is amplified when designing and developing new solutions for the industry.

The FDA hosted a webinar in April to better understand the patient and caregiver experience associated with finding and participating in gene therapy clinical trials, and the risks and benefits of participation. Clinical Trials: The Patient Experience was facilitated by Dr. Rosa Sherafat with invited panelists: Bobby Wiseman (hemophilia patient with comorbidities HepC and undetectable HIV), Suzette James (parent of two children with CLN2 Batten disease), Shandra Trantham (Friedreich's Ataxia), and Jennie Landsman (parent of two children with Canavan disease).

Many of the conditions for which gene therapy is being utilized are considered rare diseases, presenting further challenges that are well described in previous literature. It’s clear from all of the speakers that community plays a substantial role.

Online communities help bring together similarly affected populations. These communities afford a means of support and serve as a repository for information, including learning about gene therapy clinical trials. Caution is necessary when interacting in online communities as there may be more than one organization in any given disease space—each with competing interests. This leaves patients with skewed information and may not include all options. Creation of unified registries with an unbiased presentation of all available information represents an area of opportunity that might be more beneficial for patients.

“After the diagnosis she was told to go home and make her children comfortable. She didn’t accept that and chose to fight for her kids to get on clinical trials. She researched a great deal with her husband and found clinical trials on the internet.”

Restrictive eligibility criteria with seemingly arbitrary age cut-offs is cause for concern among parents. The need to travel long distances for treatment impacts the patient and caregiver—and the logistics of arranging for the needs of other family members is burdensome. Placebo arms, even when crossover is built into the trial, is frightening. When surgery is required, asking patients to consent to “sham” surgery is not an acceptable option.

“Maya was too old to participate in a clinical trial and the compassionate use program had a wait time of 2-3 years.”

Using natural history studies to assemble synthetic control arms in homogeneous diseases with known rates of progression is preferable to subjecting patients to placebo arms or sham surgeries and might help to mitigate some of these concerns. Providing advance copies of informed consent documents for review by potential patients and/or their caregivers was mentioned by more than one presenter as a welcome option. The volume of paperwork that may be provided when patients are seeking answers to specific issues is overwhelming.

“Consent forms should be sent to the patient ahead of time so the patient can read over it in advance and decide if they want to participate in the trial. The first treatment that the FDA approved for her disease was in February 2023. She states, ‘it slows progression but is not a cure.’”

Some of the presenters raised significant amounts of money to support researchers. The money and the advances were lost when the researcher relocated to a new institution. In one instance, the sponsor opted to move the trial to another country, causing significant anxiety as that was the only available treatment trial. A compassionate use request to the sponsor may be the only option and is difficult to obtain.

“The parents fund research because there are no other options and no time to wait. Suzette's advice to parents advocating for their kids is don’t be afraid to ask questions and to continue to push for answers”

In some instances, other therapies may be sought to slow disease progression while awaiting a potentially curative gene therapy trial to open. There is anxiety associated with this, as patients wonder if gene therapy will work once the disease has progressed beyond a specific but unknown point. It’s a lengthy process to open gene therapy clinical trials, conduct them, and analyze the data. Even using accelerated pathways, the regulatory process for approval is too slow for patients, particularly in progressive disease with well understood trajectories. 

“It slows progression but is not a cure.”

In addition, there are unique challenges when consenting to gene therapy. Most notably for patients, entering gene therapy clinical trials excludes participation in any future gene therapy trials as there is no way to determine which therapy may be causing any downstream effects. Gene therapy does not clear the body; unintended changes to the DNA may be passed onto future generations. The trials must be well designed and well executed, as the need to get it right on the first try is of utmost importance. Second attempts to introduce the same therapeutic would likely result in an attack of the therapeutic agent by the body.

Much of the support and information is being shared on social media platforms (primarily Facebook and Instagram) where the information is not protected, and indeed may be sold. The registries are owned by the advocacy organizations and are frequently funded by sponsors, which may represent a conflict of interest. There appears to be a multitude of opportunities to help these communities with well constructed tools that would benefit both patients and sponsors.

“Come in with grace and honor the community”

There is an element of urgency surrounding life-limiting diseases that frequently dictates risk tolerance as it pertains to clinical trial participation. Time is of paramount concern. Parents are sometimes told they will make poorly educated choices out of desperation when the only other option is certain death and these remarks are somewhat demeaning. Suzette James shared during her presentation:

“Why is it ok to make these decisions about how our child dies, but not okay to make these decisions about how our child lives?”

In the words of patient advocate and presenter Bobby Wiseman:

“It’s not about the trial itself, but (it’s) about the shift of life.”

FDA listening sessions are a way to stay up to date on key events in the industry. The FDA’s goal with these sessions is to better understand a therapeutic area by gathering key voices impacted by the condition. This is an opportunity for patients and caregivers to provide their perspectives on what’s working and not working when it comes to developing new treatments and solutions for their disease states.