Prader-Willi panel
Jamie Cox (left) and other parents of patients with Prader-Willi syndrome (PWS) participate in a panel discussion at the Externally-Led Patient-Focused Drug Development meeting on PWS. (Photo by Terri Airov)

ORLANDO, Fla.—Patients with Prader-Willi syndrome (PWS) and their families are in such dire need of new treatments that they are willing to accept the potential risks they may carry.

This was the primary message to emerge from an Externally-Led Patient-Focused Drug Development (EL-PFDD) meeting held in conjunction with the Prader-Willi Syndrome Association (PWSA) 2023 National Convention. About 250 in-person attendees and 170 virtual participants attended the meeting, which was sponsored by the US Food and Drug Administration (FDA).

Both patients and caregivers shared emotional stories describing the wide-ranging and lifelong impacts of the condition, which can result in hyperphagia, emotional outbursts, orthopedic issues, and a slew of other physical and behavioral complications. They asked the FDA to exercise more flexibility in deciding whether to approve treatments and setting outcomes in clinical trials, and to let families decide if the risks treatments may carry are worth taking.

Jamie Cox described how her daughter Zoe, a 12-year-old who just finished 6th grade, has benefited from a potential PWS treatment she has been receiving during an ongoing clinical trial. Zoe can visit with friends independently, and the “noise” associated with PWS has been quieted, she said.

“Absolutely the risk has been worth it for us and I would do it again in a heartbeat,” said Cox, one of several parents of patients with PWS who participated in a panel discussion.

A Higher Tolerance for Risk

Attendees said the immense struggles they face in managing the symptoms of the disease give them a higher threshold for risk than others may have.

“To the FDA, we appreciate the opportunity to share our stories today but we need options. We need medications,” said Paige Rivard, MBA, CEO of the PWSA. “We are willing to take risks and we need to move the needle now.”

Paige Rivard, MBA, CEO of the Prader-Willi Syndrome Association (Photo by Terri Airov)

Young people with PWS yearn for independence and want to experience life as their families and friends do, she said.

“Modest change could be life-changing,” she added. “We are good families living under unbearable circumstances.”

Speaking on behalf of the Pediatric Endocrine Society, Jennifer Miller, MD, said “we as healthcare providers … would like to see the FDA exercise more judgment in the review process of drugs for rare diseases like Prader-Willi syndrome.”

“It’s become very apparent to me that once safe and effective medications are approved by the FDA, individuals with PWS can have a prosperous and possibly even independent life as an adult, and that’s what we all want for our kids,” she said.

Dr. Miller is a professor of pediatric endocrinology at the University of Florida in Gainesville who follows more than 600 people from around the world with PWS. She said it is difficult to establish good measures in PWS clinical trials because of the many different stages of the disease and the stages of life it affects.

“We want the focus to be on safety rather than these outcome measures, because the outcome measures, as I said, are very difficult to attain … statistically significant positive results from.”

Currently, human growth hormone for growth failure is the only therapy approved to be used in PWS. But, Dr. Miller said, the medication does not address the core elements of PWS—hyperphagia and behavioral issues.

A Historic Dialogue

Patricia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research (CDER), spoke via Zoom at the start of the meeting, which she said has been in the works for more than a year.

“This type of direct dialogue is extremely important to us. I see this meeting as really being foundational in shaping how we will be communicating going forward,” she said. 

“We share across FDA, not only within CDER but all of the agencies and other centers, the community’s sense of urgency that there needs to be more safe and effective therapies for Prader-Willi syndrome and we’re here today to learn from you and your experiences.”

Dr. Cavazzoni said PFDDs were started about a decade ago by the FDA as part of the 21st Century Cures Act to gather information from patients and their families about patients’ experiences and conditions. The agency has held 30 PFDDs, and groups such as the PWSA have held more than another 80, she said.

Patricia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, speaks via Zoom at the Externally-Led Patient-Focused Drug Development meeting on Prader-Willi syndrome.(Photo by Terri Airov)

“What we have learned from these meetings is that patients and caregivers are the true experts in the lived experience of their condition and that they are uniquely positioned to inform regulatory agencies like FDA of the burden of disease and what matters most when it comes to therapies,” she said.

The FDA assists drug developers in designing clinical trials, and deciding which endpoints to use is an important part of study design, Dr. Cavazzoni said. 

“Therefore, having this kind of dialogue is extremely valuable for us because it is critical for us to hear what patients and caregivers care about, and use that information to guide developers as they make decisions about their programs, including what endpoints to use, how to run their trials, how to select the patient population, and so on,” she said. 

“It is also critically important for us as we try to understand how to facilitate the development of treatments for Prader-Willi to understand how patients and caregivers view the benefits and risks of therapies for this condition and how they weigh the benefit and risk balance when we consider potential therapeutic options.”

Calling the meeting “historic,” Rivard said it “will help us all better understand and characterize the experience of living with PWS.”

“It is our hope that today’s meeting will assist in delivering better clinical trials with meaningful outcome measures that will ultimately yield treatments and improve the quality of life for individuals affected by Prader-Willi syndrome,” she said.

The outcome of the meeting will be a “Voice of the Patient Report” to be published in the future. Caregivers of patients with PWS can submit testimonials here.


Externally-Led Patient-Focused Drug Development meeting. June 22, 2023. Orlando, FL.