Due to the results of the phase 3 clinical trial on the Zafgen drug beloranib, a meeting was recently held in Miami to review the data and meet with thrombosis experts. This was followed up by a meeting with PWS caregivers, many of whom had children on the clinical trial.
As reported in the webinar hosted by PWSA (USA) and FPWR, the effects of the drug regarding the hyperphagia (uncontrollable drive to eat) and the obesity, were remarkably positive – but there were 2 sudden deaths from pulmonary embolisms/PEs (one during the randomized part of the clinical trial and one during the 2nd six-month open label period) and 2 deep vein thrombosis/DVT events. Understandably, the FDA put the trial on a full clinical hold until decisions could be made regarding the safety of beloranib.
There is also the issue of blood clot risk in PWS in general. Dr. Jim Loker reported at the meeting that the PWS study of death has recently confirmed that approximately 7% of our people with PWS died from PEs, and possibly more actually had PEs at the time of death. The risk seems to be highest in adults who are obese and have a history of leg edema (swelling). Due to this new concern, there is an extensive survey on blood clots in PWS which can be filled out online plus paper copies are going to over 5000 families.
There were two intense days of meetings with the physicians, study coordinators and their statisticians who participated in the clinical trials along with the non-PWS thrombosis experts and Zafgen staff. A few PWS experts from Europe were also included. Theresa Strong and Janalee Heinemann represented the patient advocacy groups. No specific conclusions were reached, but the positive effects of the drug were reviewed and the safety risks were extensively discussed. A review of the current understanding of thrombotic events (DVT and PE) was provided, including risk factors, monitoring and prevention. It was clear that several issues need to be addressed before Zafgen can go back to the FDA with a plan to potentially move forward with the drug.
The PWS Caregiver Summit had strong testimony from parents about the positive effects they felt beloranib had on their children, and their dismay about having to stop the drug. With regret, they appreciated that the potential risk is too high at this point to consider putting their child back on beloranib in the near future, but they expressed interest in determining if the risks could be adequately mitigated in the future.
We appreciate Zafgen pulling together this diverse group of experts and allowing open discussion on all of the issues. For the company’s sake and for the sake of our loved ones with PWS, it is imperative that an understanding of the blood clot risk factors in PWS are defined, and that there is a way to mitigate the potential for risk before there is any consideration of moving forward with this drug that looked so very promising.
Janalee Heinemann, MSW
PWSA (USA) Coordinator of Research and International Affairs
Theresa Strong, PH.D.
FPWR Chair of Scientific Advisory Board
Jennifer Bolander has been serving as a Special Education Specialist for PWSA (USA) since October of 2015. She is a graduate of John Carroll University and lives in Ohio with her husband Brad and daughters Kate (17), and Sophia (13) who was born with PWS.
Perry A. Zirkel has written more than 1,500 publications on various aspects of school law, with an emphasis on legal issues in special education. He writes a regular column for NAESP’s Principal magazine and NASP’s Communiqué newsletter, and he did so previously for Phi Delta Kappan and Teaching Exceptional Children.
Evan has worked with the Prader-Willi Syndrome Association (USA) since 2007 primarily as a Crisis Intervention and Family Support Counselor. Evans works with parents and schools to foster strong collaborative relationships and appropriate educational environments for students with PWS.
Dr. Amy McTighe is the PWS Program Manager and Inpatient Teacher at the Center for Prader-Willi Syndrome at the Children’s Institute of Pittsburgh. She graduated from Duquesne University receiving her Bachelor’s and Master’s degree in Education with a focus on elementary education, special education, and language arts.
Staci Zimmerman works for Prader-Willi Syndrome Association of Colorado as an Individualized Education Program (IEP) consultant. Staci collaborates with the PWS multi-disciplinary clinic at the Children’s Hospital in Denver supporting families and school districts around the United States with their child’s Individual Educational Plan.
Founded in 2001, SDLC is a non-profit legal services organization dedicated to protecting and advancing the legal rights of people with disabilities throughout the South. It partners with the Southern Poverty Law Center, Protection and Advocacy (P&A) programs, Legal Services Corporations (LSC) and disability organizations on major, systemic disability rights issues involving the Individuals with Disabilities Education Act (IDEA), Americans with Disabilities Act (ADA), and the federal Medicaid Act. Recently in November 2014, Jim retired.