The PWS-Clinical Trial Consortium (PWS-CTC ) met with FDA during a 90-min session at the FDA’s White Oak Campus in Silver Spring, Maryland, to discuss the progress made in the last three years by the Consortium to overcome clinical trial challenges in PWS. With an increasing number of clinical trials in PWS it is a critical time for the FDA and industry partners to fully understand the unmet medical needs and the impact that PWS has on those with the disorder and their families.
The Critical Path Innovation Meeting (CPIM) is one way for those involved in drug development (pharma company representatives, patient groups, and university researchers) 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. CPIMs are a venue to get FDA`s perspective as well as advice on opportunities or issues.
The PWS-CTC CPIM 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.
During the first 30 min of the meeting, we presented the work performed by the Consortium in the last 3 years. Dr. Nathalie Kayadjanian, the Executive Director of the Consortium, started off with an overview of PWS and the context in which the consortium was launched. Dr. Lauren Roth-Schwartz from FPWR explained the behavioral complexities of PWS in more detail and discussed the challenges of measuring these behaviors in the context of clinical trials. She gave a brief overview of the new questionnaires that are being developed in collaboration with the PWS-CTC, including those by the Dykens`s group to capture the strategies caregivers use to control their child`s food environment (FSZQ), a new measure of rigid thinking (MERS-PWS) developed by Drs. Taylor and Hollander, and the new anxiety and distress measure (PADQ) developed by Levo Therapeutics in collaboration with FPWR. Dr. Theresa Strong from FPWR summarized the work that the Consortium has undertaken to illustrate the challenges that individuals with PWS and their families are facing across lifespan, studies that have been performed to assess caregiver`s perspectives on the impacts of PWS on their lives, treatment priorities and levels of risks families are willing to take with regards to treatment benefits, and the work that the Consortium has initiated this year in collaboration with E. Roof to gather the perspectives of individuals with PWS themselves on how PWS impacts their lives, and what new medications should address.
Major topics of discussion during this CPIM-FDA meeting included the manifestations characteristic of PWS and the understanding of concepts such as hyperphagia, anxiety and rigidity that are commonly used by the PWS community to describe PWS behaviors. FDA suggested the need for the PWS community to come to consensus definitions of these concepts as they may impact how the drug will be considered by the regulatory agency. The ability of individuals with PWS to self-report on how PWS impacts their lives was another major topic of discussion. Despite intellectual challenges faced by this population in general along with the limited self-awareness, the consortium felt that the work that it has initiated last year, thanks to the leadership of E. Roof, to document the perspectives of individuals with PWS will help the agency to have a better grasp on the needs of those with PWS, as well as the capabilities and limitations of individuals with PWS to self-report. Finally, the FDA appreciated the efforts made by the Consortium to use scientific methodologies to measure the impact of PWS on the lives of caregivers and their priorities regarding treatments for their loved ones.
The level of commitment that the FDA showed during the meeting was impressively clear in our interactions with them and their willingness to interact with the Consortium on a regular basis. PWS is on the FDA agenda thanks to the Consortium and the multiple ongoing clinical trials. The core activities of the PWS-CTC, which have centered on the development of measures to best assess the efficacy of a treatment in clinical trials (what we call endpoints) and on studies to measure the views of patients and caregivers, are aligned with the FDA's patient-focused drug development mandate. Three years after its creation, the Consortium is delivering results as a unique collaboration between experts from industry, academia and patient representatives. The meeting with the FDA was also a great opportunity for the different stakeholders of the consortium to come together as a unified voice in the dialog with FDA to explore ways to leverage its work and ultimately benefit the entire PWS community.