Zevra testing beta blocker celiprolol for vEDS in Phase 3 US study
19 vascular Ehlers-Danlos syndrome patients now enrolled; trial recruiting
Zevra Therapeutics has been enrolling and dosing new patients in a Phase 3 clinical trial testing celiprolol, a beta blocker being developed for people with vascular Ehlers-Danlos syndrome (vEDS) caused by mutations in the COL3A1 gene.
The trial, dubbed DiSCOVER (NCT05432466), is assessing how well celiprolol works compared with a placebo to reduce the time to a medical emergency.
As of the end of September, 19 patients were participating in the U.S. study, Zevra noted in a press release reporting the company’s latest financial results.
“The third quarter [of this year] was one of the most exciting and transformational periods in Zevra’s journey,” said Neil F. McFarlane, Zevra’s president and CEO.
The company acquired the rights to celiprolol from Acer Therapeutics in 2023, and says it is now working to strengthen and expand its collaborations with patient advocacy groups, specialized treatment centers, and medical experts to broaden awareness about the disease.
The pivotal clinical trial, which is running under a special protocol assessment agreement with the U.S. Food and Drug Administration (FDA), is recruiting at a site in California. With the agreement, the FDA recognizes that DiSCOVER is designed such that it could support an application for marketing approval of the treatment candidate, according to Zevra.
DiSCOVER trial testing celiprolol expects to enroll 150 vEDS patients
In addition to overly flexible joints and loose skin — symptoms common to other types of Ehlers-Danlos syndrome, a group of genetic conditions that cause defects in the body’s connective tissues — people with vEDS have fragile internal organs and blood vessels that are prone to rupturing and bleeding. This type of the disease is often caused by mutations in COL3A1, which codes for part of a protein that helps tissues hold together.
Celiprolol, previously also known as ACER-002 or Edsivo, is a beta blocker that works by allowing blood vessels to relax and widen. This is expected to lower pressure in blood vessels and reduce the risk that they will rupture or tear. While celiprolol is not approved for vEDS, it is often used as an off-label treatment.
The treatment candidate has previously been tested in a Phase 4 clinical trial (NCT00190411) in France. Participants in that study were treated with celiprolol twice daily, starting at a dose of 100 mg, which was increased every six months by steps of 100 mg to a maximum of 400 mg per day.
The results showed that treated patients were nearly three times less likely to experience a blood vessel rupture or tear compared with those who were not treated.
Despite these positive data, the FDA turned down Acer’s application for celiprolol’s approval in the U.S. The regulatory agency recommended the company design a well-controlled clinical trial to determine whether the investigational beta blocker could reduce the risk of clinical events related to vEDS.
As part of DiSCOVER, an estimated 150 patients with a diagnosis of vEDS and carrying a disease-causing mutation in COL3A1 are being randomly assigned to either celiprolol or a placebo. The medication is being given twice daily at a starting dose of 100 mg, which is increased each month up to 400 mg daily from month 4 onward. or a placebo. The trial is open to patients ages 15 and older.
The main goal is to determine if celiprolol reduces the occurrence of clinical events that require medical intervention relative to the placebo over an estimated 40 months, or nearly 3.5 years. Among the events being monitored are rupture of blood vessels or the heart, uterus, or bowel, as well as unexplained sudden death.
The FDA has named celiprolol a breakthrough treatment for vEDS caused by mutations in the COL3A1 gene. That designation is granted to a treatment for a serious or life-threatening disease when early evidence suggests it could offer benefits over available treatment options. The therapy also was awarded orphan drug status for the treatment of vEDS, a designation that confers certain incentives to companies developing treatments for rare diseases.
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