Vaderis Reports Positive Clinical Proof-of-Concept Trial in HHT

Vaderis Therapeutics AG has announced promising results from its first industry-led clinical trial for Hereditary Haemorrhagic Telangiectasia (HHT), an inherited bleeding disorder with no currently approved treatment options. This trial, a randomized, double-blind, dose-finding, placebo-controlled Proof-of-Concept (POC) study, examined the efficacy and safety of VAD044, an oral allosteric AKT-inhibitor specifically designed to treat HHT.

HHT is the second most common inherited bleeding disorder globally, resulting in a severe disease burden, reduced life expectancy, and impaired quality of life. Despite its prevalence, no approved treatments exist for HHT. VAD044 aims to address this unmet need by offering a novel therapeutic option.

In the clinical trial, seventy-five patients from the USA and Europe were randomized to receive either a placebo, 30mg, or 40mg of VAD044 for a 12-week period. The primary endpoint was safety, and VAD044 demonstrated a safety profile comparable to the placebo, with the frequency and severity of adverse events (AEs) similar between the groups. Any AEs associated with AKT pathway inhibition were generally mild, transient, and resolved while still on the study drug.

A key measure of HHT disease burden is epistaxis, or nosebleeds, which are unpredictable, frequent, and often debilitating for patients. VAD044 showed a dose-responsive improvement in secondary and exploratory efficacy endpoints, notably epistaxis-related measures. Patients on the 40mg dosage exhibited significant clinical improvements in the frequency, duration, and number of epistaxis-free days. Additionally, regression in HHT-associated vascular lesions was observed by the end of the 12-week treatment.

Following the initial 12-week double-blind phase, patients from selected study centers were enrolled in a 12-month Open Label Extension (OLE) where they received up to 40mg of VAD044 daily. Interim data at the 6-month mark continued to indicate favorable safety and tolerability, with further improvements in epistaxis measures.

Dr. Hanny Al-Samkari, a hematologist/oncologist at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School, who co-led the VAD044 POC trial, noted the significant and clinically meaningful dose-dependent improvements in HHT disease activity observed as early as 12 weeks, particularly in epistaxis parameters.

Dr. Hans-Jurgen Mager, a pulmonologist and head of the Netherlands Reference Centre for HHT, also co-primary investigator of the trial, added that the ongoing results from the OLE indicate continued patient improvements over time without compromising safety or tolerability.

Nicholas Benedict, CEO and co-founder of Vaderis Therapeutics, expressed excitement about the trial's initial 12-week results and the continued positive outcomes at 6 months. He emphasized the importance of collaboration with patient and physician organizations such as CureHHT, which was instrumental in the rapid and successful implementation of this pioneering trial. Vaderis Therapeutics is now engaging with major health authorities to plan the pivotal phase of VAD044's development for treating HHT.

Vaderis Therapeutics is committed to developing treatments for rare and orphan diseases associated with vascular malformations, such as HHT. By focusing on diseases driven by overactivation of AKT due to upstream genetic mutations, Vaderis aims to bring groundbreaking treatments to patients who currently have no approved options. VAD044 is poised to become the first approved medication specifically for HHT, marking a significant advance in the field of rare disease therapeutics.

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