Vaderis Drug Reduces Nosebleeds in Rare Blood Vessel Disorder Trial

Hereditary hemorrhagic telangiectasia (HHT) is the second most prevalent inherited bleeding disorder globally, associated with significant disease burden, decreased life expectancy, and diminished quality of life. Vaderis Therapeutics has taken a significant step toward developing the first targeted drug for this rare blood vessel disorder with the announcement that their therapy, VAD044, is both safe and effective in reducing nosebleeds.

VAD044, a once-daily allosteric AKT inhibitor, was tested in a trial involving 75 patients with HHT. This genetic disorder leads to the formation of abnormal blood vessels in the skin, mucous membranes, and certain organs. Nearly all HHT patients experience unpredictable and often debilitating nosebleeds. After 12 weeks of treatment, patients who received a 40-mg dose of VAD044 showed "clinically meaningful" reductions in the frequency of their nosebleeds, which was a secondary endpoint of the trial. Although the company did not release specific data, they did note that the regression of HHT-associated vascular lesions was observed.

The phase 1 trial had three groups: patients receiving a 40-mg dose, those receiving a 30-mg dose, and those given a placebo. The primary endpoint was safety, and VAD044 demonstrated a similar safety profile to the placebo with regard to the frequency and severity of off-target adverse events. On-target adverse events related to inhibiting the AKT pathway were mostly mild, transient, and resolved over time.

Some patients have enrolled in a 12-month open-label extension, receiving a daily dose of 40-mg VAD044. Interim six-month data from 27 patients indicate continued favorable safety and tolerability profiles, with further improvements in nosebleeds. CEO Nicholas Benedict stated that the company is already engaging with major health authorities to plan the pivotal phase of VAD044's development for HHT.

Benedict expressed excitement about the results from the initial 12-week double-blind part of the trial, amplified by continued patient improvements over six months. Despite the severe impact of HHT, there are currently no approved treatments for the condition. Vaderis describes VAD044 as the first novel therapy specifically intended for treating HHT. The company is also planning to test the therapy in breast and prostate cancers.

Hans-Jurgen Mager, M.D., Ph.D., head of the Netherlands Reference Centre for HHT and the study’s co-primary investigator, noted that patients experience continual improvements even after six months of VAD044 treatment. Mager emphasized that VAD044 seems to have not yet reached its peak effect on HHT disease activity at the 12-week mark. Patients continue to improve over time without encountering unexpected safety or tolerability issues.

In parallel, academic centers in the U.S. are enrolling patients to test whether Novartis' sarcoma drug, Votrient, can reduce the severity of nosebleeds in HHT. Votrient is a tyrosine kinase inhibitor that has shown efficacy in inhibiting the PI3K/Akt signaling pathway.

Notably, Vaderis was established in 2019 by two veterans of Novartis, including CEO Nicholas Benedict, indicating a direct link to the Swiss pharmaceutical giant.