Report on the Zafgen Meetings

Due to the results of the phase 3 clinical trial on the Zafgen drug beloranib, Zafgen recently held a meeting in Miami to review the data from the trial and meet 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 meetings to discuss the findings of the ‘bestPWS’ Phase 3 study, in which 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.  The PWS Caregiver Summit had strong testimony from parents about the positive effects they felt beloranib had on their children, in some cases quite dramatic, 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 consideration of moving forward with this drug that looked so very promising.

Theresa Strong, Ph.D

FPWR Director of Research Programs

Janalee Heinemann, MSW
PWSA (USA) Coordinator of Research and International Affairs