Advocating for New Prader-Willi Syndrome Treatments

Yesterday, Today and Tomorrow

Perhaps now, more than ever before, we are beginning to see the fruits of more than a decade of advocacy work. With your support, FPWR has been working diligently to build a "research-ready" community, with resources that address the FDA’s call for patient experience data, demonstrate the high disease burden of PWS and establish the need for effective therapies. Our ultimate goal: the successful approval of new treatments for PWS.

How Do We Effectively Advocate for New Treatments for PWS?

Advocating for new treatments for PWS needs to happen all the way across the drug development and approval pathway in order to achieve optimal effect. Such an approach will ensure that new treatments developed for PWS will have a meaningful impact on our loved ones. This means working with pharmaceutical companies to help them understand the medical needs of the PWS community and the aspects of PWS that families want to see treated. It also requires establishing a strong relationship with the Food & Drug Administration (FDA), whose job it is to determine if a drug is safe and effective for the PWS. The FDA does this by weighing the benefits and risks of any new drug, in the context of the unmet medical needs of the patient population who will potentially be taking the drug.

Regulatory scientists at the FDA have to review treatments for many, many different disorders so they seek input from the patient community about what the medical needs of patients are, what a meaningful outcome would be, and what level of risk individuals are willing to accept for the potential benefit they might receive from a treatment. With the 21st Century Cures Act, the opportunities for patients to provide input to FDA were strengthened and formalized, and the FDA has established programs to encourage Patient-Focused Drug Development.

The FPWR team has been working to gather information about the PWS patient and family experience and preferences to share with pharmaceutical companies and the FDA to help accelerate the development of meaningful new treatments for PWS. Our efforts include:

  1. Documenting the medical need, voice, and preferences of the PWS community
  2. Continued dialogue with industry sponsors to advance trials for PWS
  3. Continued dialogue with the FDA to advocate for new treatments for PWS
  4. Providing expert perspective
PWS Advocacy Activities (7)

1. Documenting the Medical Need, Voice, and Preferences of the PWS Community

For more than a decade the FPWR has partnered with families and other PWS groups (PWSA|USA, IPWSO) and worked diligently to build resources that address the FDA’s call for patient experience data, demonstrating high disease burden and the need for effective therapies addressing hyperphagia. We have demonstrated through family stories, surveys, and a more formal, best-worst scaling study  that hyperphagia is “the” aspect of PWS that families want addressed through new therapies, followed by other critical behavioral issues such as anxiety and aggression.

We have demonstrated the tremendous unmet medical needs of individuals with PWS, and the considerable burden of disease, showing that caregiver burden in PWS exceeds that of caregivers for stroke and Alzheimer disease (Kayadjanian et al 2018) and that higher levels of hyperphagia are associated with increased caregiver burden (Kayadjania et al 2021).

We have also demonstrated that caregivers are willing to accept considerable risk in exchange for modest improvements in hyperphagia (Tsai 2021).

Finally, as suggested by the FDA during a Critical Path Innovation Meeting, we have also solicited input from individuals with PWS, speaking on their own behalf. Although this was challenging (not all individuals are capable of expressing their views), Dr. Elizabeth Dykens and her team elicited opinions from young adults with PWS on treatment preferences and disease burden, which strongly align with that of caregivers (Dykens 2021). This patient experience data is complemented by natural history studies that provide critical information to support clinical trials, including a study funded by the National Institutes of Health (led by Dr. Dan Driscoll, 2006-2014) as well as an ongoing registry-based prospective study of behavioral changes over time and serious medical events (PATH for PWS).

Publications and Resources to Support Approvals of Treatments for PWS
  1. PWS Across the Lifespan. The diversity and complexity of the clinical manifestations of PWS along with the life-long impact of PWS on individuals with PWS and their caregivers are often difficult to convey to healthcare professionals including regulatory agencies who are not familiar with PWS.This 20-minute film available in English, Spanish, and French illustrates the complexity and challenges of PWS on the individual with PWS and their families.

  2. Impact of PWS on Individuals and Their Families and Views on Treatments: Results of an International Online Survey. This survey of more than 750 parents and caregivers of individuals with PWS captured the symptoms associated with PWS that affect day-to-day living, the impact of PWS, the effectiveness of current medications, and attitudes towards clinical trials.

  3. Caregiver Priorities for Endpoints to Evaluate Treatments for Prader-Willi Syndrome: A Best-Worst Scaling. A national online survey of caregivers identified caregiver priorities for potential treatment and quantified caregiver preferences for the benefits and risks of treating PWS. Findings from this report indicate hyperphagia is “the” aspect of PWS that families want addressed through new therapies, followed by other critical behavioral issues such as anxiety and aggression.

  4. High Levels of Caregiver Burden in Prader-Willi Syndrome. Caregivers of children and adults with PWS were surveyed using the Zarit Burden Interview (ZBI) in order to measure the level of burden in caregivers of individuals with PWS, to explore the impact of PWS on caregiver quality of life, and to assess the ZBI as an indicator of that impact. Results from this survey show caregiver burden in PWS exceeds that of caregivers for stroke and Alzheimer disease.

  5. Characteristics and Relationship Between Hyperphagia, Anxiety, Behavioral Challenges and Caregiver Burden in Prader-Willi Syndrome. This paper demonstrated that higher levels of hyperphagia in individuals with PWS are associated with increased caregiver burden.

  6. PWS Caregiver Risk Tolerance: Academic Perspective on Patient Preference Research. This study, supported by the PWS-CTC evaluated potential treatment benefits and the amount of risk the community was willing to take for each. This publication establishes that caregivers are willing to accept considerable risk in exchange for even modest improvements in hyperphagia.

  7. Natural History Study of Serious Medical Events in PWS (PATH for PWS). A 4-year, ongoing, natural history study, PATH for PWS will help us to better understand serious medical events in people with PWS ages 5 and up, and will evaluate how PWS-related behaviors change over time.

  8. Impact of COVID on the PWS Community. The Global PWS Registry launched a survey in summer 2020 to capture the impact of COVID-19 on PWS families. We found COVID-19 had a profound impact on people with PWS which likely impacted the conduct and outcome of PWS clinical trials taking place during that time.

  9. Behavioral Features in Prader-Willi Syndrome (PWS). This paper presents consensus definitions and descriptions of key PWS behaviors, from a group of international PWS academic investigators and clinicians who are part of the PWS Clinical Trials Consortium. Behavioral features including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity and social cognition deficits are discussed.

  10. ‘The Cure for Us Is a Lot of Things’: How Young People with Prader-Willi Syndrome View Themselves and Future Clinical Trials. This paper discusses the outcome of semi- structured interviews with twenty-one adolescents/young adults with PWS that captured their perspective on PWS, and thoughts about clinical trials and possible treatments for PWS.

In April 2021, FPWR and PWSA | USA submitted a request to the FDA asking them to apply regulatory flexibility when reviewing potential new treatments for PWS.

The 143-page letter included more than 26,000 signatures from community supporters around the globe and comments from trial participants and PWS community members.


2. Continued Dialogue with Industry Sponsors to Advance Trials for PWS

FPWR has regular interaction with pharmaceutical companies who may have an interest in developing new treatments for PWS, with the aim of educating the companies about PWS and helping them develop successful clinical trials that minimize burden on participants. Our goal is to provide the patient perspective to facilitate the development of treatments that are safe and effective for PWS, helping to advance potential treatments for PWS into clinical trials and beyond. We have spent hundreds, perhaps even thousands, of hours on the phone and in person, talking with companies about PWS, helping them understand PWS and the unmet needs of our community, facilitating clinical trial design and working to develop trials that have the best chances for success. We work with each company to de-risk the drug development process and speed up the timeline to taking a drug to the FDA for approval. We are committed to working with any company that has the potential to develop a medical product that might benefit individuals with PWS.

FPWR has been recognized for its productive collaboration with industry by the Clinical Trials Transformation Initiative, an organization comprised of more than 80 organizations from across the clinical trial enterprise with the mission to develop and drive adoption practices that will increase the quality and efficiency of clinical trials.

3. Continued Dialogue With the FDA to Advocate New Treatments for PWS

PWS is a complex rare disease that, as our community is well aware, is nuanced and not immediately understandable by people outside of our community. It is critical that the FDA fully understand how PWS impacts those with the disorder and their families so FPWR, PWSA |USA, and key leaders in the scientific community have held several meetings with the FDA to share the serious challenges of PWS and our loved ones’ unmet medical needs, and to bring the perspective of the PWS patients and caregivers to the FDA for their evaluation of new candidate drugs for PWS.  

    • Introductory Meeting [2008]
      In April 2008, three of the co-founders of FPWR, Alice Viroslav, Lauren Schwartz-Roth, and Theresa Strong, met with the FDA Director of Orphan Products, Dr. Tim Cote, and his staff at the FDA to discuss the unmet medical needs in the PWS community and how new medical products for PWS should be developed and evaluated. This productive meeting set the stage for ongoing engagement towards the common goal of bringing safe and effective treatments to PWS

    • June 17, 2014, Meeting with FDA [2014]
      As drug development advanced in the PWS field, this meeting was attended by approximately 15 FDA personnel, including leaders from the Center for Drug Evaluation and Research, Medical Officers, who are responsible for evaluating new drugs, members of the SEALD team (study endpoint and labeling development), and FDA staff members whose role it is to facilitate patient engagement. In the 1-hour meeting representatives from both PWSA |USA and FPWR shared experiences raising children with PWS and the tremendous challenges they face everyday. We left the attendees with a comprehensive packet of information on PWS for their reference and took away specific ideas on how to engage the PWS community in order to bring valuable information back to the FDA.

    • PWS-CTC Workshop [2015]
      In 2015 FPWR organized a workshop gathering 34 international participants from industry, academia, patient organizations, non-governmental organizations and FDA to discuss about opportunities and identify key challenges for current and future PWS clinical trials with the aim of creating an international precompetitive collaborative consortium working on key issues identified during the workshop. Four topics were discussed during the workshop including natural history of PWS, clinical trial endpoints, clinical trial design and benefit/risk assessment.

    • PWS-CTC Critical Path Innovation Meeting [2018]
      Most recently, members of the PWS Clinical Trials Consortium, which is comprised of patient organizations, industry sponsors and PWS researchers, met with the FDA for a 90-minute Critical Path Innovation Meeting. The meeting was attended by more than ten FDA personnel, including leaders in the Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Biostatistics, Office of New Drugs, Clinical Outcome Assessment Staff, and the Office of Drug Evaluation II. Twenty-two consortium members attended the meeting including patient representatives from FPWR, PWSA(USA), and IPWSO, industry representatives from Zafgen, Levo, Soleno, Rhythm, Insys, Saniona and Millendo, as well as several members from academia including Drs A. Dimitropoulos, C. Höybye, J. Duis, A. Caixas, and B. Taylor. The purpose of the meeting was to meet with FDA to discuss general issues such as methodology, technology or strategies in drug development, outside of the context of review for any particular medical product and get the FDA`s perspective as well as advice on opportunities or issues.

    • FDA Patient Listening Session [2021]
      On June 17, 2021, FPWR and PWSA | USA engaged the FDA in a Patient-Led Listening Session to share our community’s experiences related to PWS. The purpose of this meeting was to promote dialogue between the FDA and members of the PWS patient community to ensure the FDA has a full understanding of the unique challenges of PWS and issues related to clinical trials.

4. Providing Expert Perspective

The FPWR team has also participated in meetings of pharmaceutical companies with FDA, providing the patient perspective in discussions about the development of specific medical products. In addition, FPWR Director of Research Programs, Theresa Strong has participated as a Panelist at meetings and webinars on how patients and patient groups can advance the patient perspective in drug development, review and approval:


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The Rules of Engagement: Who Can Do What?

Patient advocacy groups must rely on industry sponsors to submit New Drug Applications to the FDA. The New Drug Application (NDA) is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale in the US. Data gathered through clinical trials of the investigational new drug (IND) become part of the NDA. The drug sponsor is the ONLY entity that can submit an NDA to the FDA.

Drug sponsors control their relationship with the FDA and when to open communications. While patient organizations can help advise drug sponsors on a variety of areas relevant to patient perspective, which can impact their drug development and clinical trial program, we cannot dictate how the sponsor chooses to interact with the FDA or the decisions the sponsor makes. Typically, pharmaceutical companies maintain strict confidentiality about the details of their interactions with the FDA and many of the specifics of their submissions to the FDA. The FDA, by law, cannot discuss or disclose any information about their interactions with drug sponsors.

The timelines for new drug approvals are out of our hands. Many factors come into play when estimating a timeline for drug review and approval. Fortunately, many drugs in clinical trials for PWS have been given Orphan Drug Designations which speeds up the review of the NDA, however, before an application can be filed, multiple conversations need to take place between the drug sponsor and the FDA. These conversations are important steps in working towards a successful approval but we must realize, it typically takes a minimum of 3 months between each and every conversation. The more conversations that are necessary to fully review the drug, the longer the process will take.

Visual Chart Page Iteration 5 (3)

For more information on who can do what, watch this 6-minute presentation by Rob Lutz, PWSA | USA board member:


What Are the Next Steps in Our PWS Advocacy Efforts?

PWS Advocacy Activities-2-1

Continue to Advocate on Behalf of the PWS Community With the FDA

Until a CURE for PWS has been found, both FPWR and PWSA | USA will continue to advocate for the advancement of new, safe and effective drugs and devices to treat the challenges our loved ones with PWS face. We will work with all pharmaceutical companies that have products that might improve the lives of those with PWS.

For example, FPWR has circulated petitions among the PWS community to request that the FDA apply regulatory flexibility and engage in further dialogue with the PWS community regarding drug development for PWS. We will continue to provide opportunities for the patient community to share their experience with the FDA. 

Continue to Collect Robust Natural History Data

The FDA, as a general standard, requires positive results in 2 controlled studies or 1 well-controlled study with confirmatory evidence, such as natural history data. The Global PWS Registry is currently collecting natural history data that may support PWS clinical trials. We need the members of the PWS community to continue to complete surveys in the Registry so that our data reflects the entire PWS population.

Continue the Work of the PWS-CTC in Defining New Trial Endpoints

Establishing additional clinical trial endpoints that accurately define what a positive result in PWS patients looks like is imperative to successful clinical trials. Clinical significance of the treatment effect and impact on aspects of PWS, other than hyperphagia, such as overall quality of life and the functioning of the participant, have not been fully explored and some interventions may positively impact different, or additional, aspects of the disorder including physical, cognitive and behavioral symptoms, which are not captured by current outcome measures. The PWS-CTC will continue to develop and evaluate new endpoints for PWS clinical trials.

What Can YOU Do to Advocate for Treatments for PWS?

PWS Advocacy Activities (1)-1

  1. Complete surveys in the Global PWS Registry. One of the greatest contributions you can make to help advance PWS clinical trials is to participate in the Global PWS Registry by completing new surveys and updating old surveys on an annual basis.

  2. Participate in sign-on opportunities to share your experience. For example, in 2021, more than 26,000 supporters signed-on in favor of an FDA review of DCCR for PWS, and comments shared through the sign-on were included in a letter to the FDA. 

  3. Participate in PWS clinical trials. There are a number of study opportunities for families to participate in. Some studies are investigating new drugs, others may be evaluating an intervention or seeking information regarding your experiences. You can keep up to date on the latest study opportunities by visiting our PWS clinical trials directory.

Ready to Take the First Step?

The Global PWS Registry is only as powerful as the people who participate. And learning more about the experiences, medications, symptoms, milestones, and other aspects of PWS is key to advancing our understanding and discovering new therapies and treatments.

Visit the Global PWS Registry for more information for researchers and patients. From there, register and be part of the global community working toward brighter tomorrows for our loved ones with PWS.

PWS global registry