Vaderis announces positive clinical proof-of-concept study in HHT

• First industry-led clinical trial in hereditary hemorrhagic telangiectasia (HHT) delivers positive results
• VAD044 demonstrated good safety and tolerability as well as exploratory efficacy in the main manifestations of the disease
• Ongoing Open Label Extension (OLE) data after 6 months show consistent safety, tolerability and continued improvement in bleeding parameters

BASEL, Switzerland, 27 August 2024 /CNW/ — Vaderis Therapeutics AG (Vaderis), a clinical-stage biotechnology company focused on developing treatments for rare diseases associated with vascular malformations, today announced positive results from its randomized, double-blind, dose-ranging, placebo-controlled proof-of-concept (POC) study in patients suffering from HHT.

HHT, a rare disease, is the second most common inherited bleeding disorder worldwide and often causes severe disease burden, reduced life expectancy and impaired quality of life. Despite this, there is still no approved treatment for HHT worldwide. Vaderis is developing VAD044, an oral, once-daily allosteric AKT inhibitor, the first novel therapy specifically designed to treat HHT.

In this controlled double-blind study, 75 patients from USA And Europe were randomized to receive either placebo or 30 mg or 40 mg of VAD044 for 12 weeks. The primary endpoint was safety, and VAD044 was similar to placebo in both the frequency and severity of adverse events (AEs). Adverse events (AEs) related to AKT pathway inhibition were mostly mild, transient, and resolved with study drug.

Almost all HHT patients experience unpredictable, frequent and debilitating nosebleeds, which are considered the best indicator of overall HHT disease activity and a key indicator of disease burden. In this study, VAD044 demonstrated a dose-response relationship with secondary and exploratory efficacy endpoints in HHT, including the key nosebleed endpoint. At the end of the 12-week treatment period, patients receiving the 40 mg dose showed clinically meaningful improvements in the frequency and duration of nosebleeds, as well as in the number of days without nosebleeds. In addition, a reduction in vascular lesions associated with HHT was observed.

Following the 12-week randomized, double-blind phase, patients from selected study centers were enrolled in a 12-month OLE study, all of which received up to 40 mg of VAD044 daily. Interim data for 29 patients at 6 months continue to demonstrate favorable safety and tolerability profiles with further improvements in epistaxis.

Dr. Hanny Al-Samkarithe Peggy S. Blitz Endowed Chair in Hematology/Oncology at Massachusetts General Hospital and Associate Professor of Medicine at Harvard University Medical School (USA), one of the principal investigators of the VAD044 POC study, commented: “In this groundbreaking clinical trial, we are seeing substantial and clinically meaningful dose-dependent improvements in HHT disease activity with once-daily VAD044, particularly as measured by epistaxis parameters, as early as 12 weeks.”

Dr. Hans-Jürgen MagerPulmonologist and head of the Dutch reference centre for HHT at St. Antonius Hospital, Amsterdam (NL), also co-principal investigator in the VAD044 POC study, added: “These exciting results have supported the evaluation of long-term treatment of HHT patients with VAD044. We have added an open-label extension to the POC study and are already seeing patients experience further improvements in all epistaxis endpoints after 6 months of continuous treatment with VAD044 compared to those seen at 12 weeks. It appears that VAD044 has not yet reached its maximum effect on HHT disease activity at 12 weeks and patients continue to recover over time without paying an unexpected price in terms of safety or tolerability.”

Nicholas BenedictCEO and co-founder of Vaderis Therapeutics, commented: “The excitement surrounding the results of the first 12-week double-blind portion of this study is further enhanced by the sustained improvements experienced by patients over the course of 6 months. The excellent collaboration with patient and physician organizations such as CureHHT was a cornerstone for the successful implementation of this groundbreaking study, which was conducted in a much shorter timeframe than planned. Vaderis is currently working with key health authorities to plan the critical development phase for VAD044 in HHT.”

About Vaderis

Vaderis is a clinical-stage biotechnology company developing treatments for rare and orphan diseases associated with vascular malformations. There are a significant number of debilitating and largely untreated rare diseases, such as HHT (Hereditary Hemorrhagic Telangiectasia), in which patients have overactivation of AKT driven by upstream genetic mutations, resulting in excessive vascular growth. Vaderis is developing VAD044, a daily oral allosteric AKT inhibitor that has been studied in a proof-of-concept clinical trial in HHT patients and is currently in a 12-month open-label extension. There are no approved drugs to treat HHT and Vaderis' goal is to be the first company to develop a drug to treat HHT and other diseases associated with vascular malformations.

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