FDA Tells Acer It Won’t Approve vEDS Therapy without Additional Trial

The U.S. Food and Drug Administration rejected rare disease drug developer Acer Therapeutics’ application for marketing approval for Edsivo (celiprolol) as a treatment for vascular Ehlers-Danlos syndrome without another trial to determine the drug’s safety.

Acer said it plans to request a meeting to discuss the FDA’s response in the third quarter of 2019.

Ehlers-Danlos syndrome (EDS) is a rare genetic disorder that affects a person’s connective tissue, which separates, connects and supports different organs in the body. It is caused by mutations in the COLA3A1 gene. People with EDS usually cannot make enough normal collagen, a connective tissue protein. Vascular EDS, or vEDS, is considered serious because blood vessels and organs tend to be fragile and rupture easily. The bowels and large arteries are prone to spontaneous rupture. In addition to loose joints and very stretchy skin, common symptoms include thin, translucent skin, easy bruising, bruising without trauma, and fragile arteries, intestine, and/or uterus. There is no cure for vEDS and persons with the disorder require life-long monitoring, including regular screening and surgery to deal with complications.

Acer’s application for approval was based on a small, 54-patient study designed to show that Edviso (the beta blocker celiprolol) could prevent arterial ruptures. It worked so well in the study that the trial was stopped early before it had enrolled the target number of patients.

In April, Acer issued a press release citing the publication of long-term data from a cohort of COL3A1 positive vEDS patients in the Journal of the American College of Cardiology that described outcomes in 144 such patients who were clinically monitored and treated at the French National Referral Center for Rare Vascular Diseases between the years 2000 and 2017. The study authors found that vEDS patients treated with celiprolol had a higher survival rate than expected relative to the known natural history of the disease and a lower annual occurrence of arterial complications, and that celiprolol use was potentially associated with these significant improvements in clinical outcomes.