Vaderis Therapeutics AG announced positive results from its randomized, double-blind, placebo-controlled Phase 2 proof-of-concept clinical trial of VAD044 in patients with Hereditary Hemorrhagic Telangiectasia (HHT). The trial, involving 75 patients across the USA and Europe, demonstrated that VAD044, an oral, once-daily allosteric AKT-inhibitor, showed a favorable safety profile and promising efficacy in reducing epistaxis, a key manifestation of HHT.
HHT is a rare genetic disorder affecting approximately 1 in 5,000 people, characterized by abnormal blood vessel formation leading to frequent and severe bleeding, particularly nosebleeds (epistaxis). Currently, there are no approved treatments for HHT, making the development of VAD044 a potentially significant advancement.
VAD044 Demonstrates Clinical Benefit in HHT Patients
The Phase 2 trial randomized patients to receive either placebo, 30mg, or 40mg of VAD044 for 12 weeks. The primary endpoint was safety, with VAD044 demonstrating a safety profile similar to placebo. Secondary and exploratory efficacy endpoints focused on epistaxis, a major indicator of HHT disease activity. Patients receiving the 40mg dose experienced clinically meaningful improvements in epistaxis frequency, duration, and epistaxis-free days. Furthermore, regression of HHT-associated vascular lesions was observed.
Dr. Hanny Al-Samkari, co-primary investigator and Associate Professor of Medicine at Harvard Medical School, noted, "In this pioneering clinical trial we see already at 12 weeks substantial and clinically meaningful dose-dependent improvements in HHT disease activity with once-daily VAD044, particularly as measured by epistaxis parameters."
Open-Label Extension Shows Sustained Improvement
Following the 12-week double-blind period, patients from selected study centers were enrolled in a 12-month open-label extension (OLE) study, receiving up to 40mg of VAD044 daily. Interim data from 29 patients at the 6-month timepoint showed continued favorable safety and tolerability, with further improvements in epistaxis endpoints compared to the 12-week results. Dr. Hans-Jurgen Mager, co-primary investigator and head of the Netherlands Reference Centre for HHT, commented that patients continue to improve over time without unexpected safety concerns, suggesting VAD044's peak effect may not be reached at 12 weeks.
Vaderis Plans Pivotal Phase Development
Vaderis is currently interacting with major health authorities to plan the pivotal phase of development for VAD044 in HHT. Nicholas Benedict, CEO of Vaderis Therapeutics, highlighted the collaborative effort with patient and physician organizations like CureHHT in achieving this milestone. The company aims to be the first to develop a medicine for the treatment of HHT and other diseases associated with vascular malformations.
