Zevra Therapeutics is currently enrolling patients in a Phase 3 clinical trial, DiSCOVER (NCT05432466), to evaluate the effectiveness of celiprolol in individuals with vascular Ehlers-Danlos syndrome (vEDS) caused by mutations in the COL3A1 gene. The trial is designed to determine if celiprolol can reduce the time to a medical emergency compared to placebo, addressing a critical unmet need in this patient population.
DiSCOVER Trial Details
The DiSCOVER trial aims to enroll approximately 150 patients with vEDS who have a confirmed disease-causing mutation in the COL3A1 gene. Participants are randomly assigned to receive either celiprolol or a placebo. The drug is administered twice daily, starting at 100 mg and gradually increasing to 400 mg daily from month four onwards. The primary endpoint of the study is to assess the time to the first occurrence of clinical events requiring medical intervention, such as rupture of blood vessels, the heart, uterus, or bowel, as well as unexplained sudden death, over a period of approximately 40 months.
Celiprolol: Mechanism of Action and Prior Research
Celiprolol, also known as ACER-002 or Edsivo, is a beta blocker that functions by promoting the relaxation and widening of blood vessels. This mechanism is expected to lower blood pressure within these vessels, consequently reducing the likelihood of rupture or tearing. While celiprolol is not currently approved for vEDS, it has been used off-label in clinical practice. A previous Phase 4 clinical trial conducted in France (NCT00190411) suggested that patients treated with celiprolol were nearly three times less likely to experience a blood vessel rupture or tear compared to those who were not treated.
Regulatory Status and Unmet Need
Despite promising data from the earlier trial, the FDA previously declined Acer Therapeutics' application for celiprolol approval, citing the need for a well-controlled clinical trial to confirm its efficacy in reducing vEDS-related clinical events. The FDA has granted celiprolol breakthrough therapy designation for vEDS caused by COL3A1 mutations, indicating that preliminary evidence suggests it may offer a significant improvement over existing treatment options. Additionally, celiprolol has received orphan drug status for the treatment of vEDS, which provides incentives for companies developing therapies for rare diseases. Currently, treatment options for vEDS are limited, and the disease carries a high risk of life-threatening vascular events, highlighting the urgent need for effective therapies.
