Vaderis Therapeutics’ goal to develop the first drug aimed specifically at a certain rare blood vessel disorder came one step closer today with the news that the therapy is safe and reduced nosebleeds.
The therapy in question, a once-daily allosteric AKT inhibitor dubbed VAD044, was trialed in 75 patients with hereditary hemorrhagic telangiectasia (HHT), a genetic disorder that leads to abnormal blood vessels forming in the skin, mucous membranes and certain organs.
Almost all HHT patients suffer from unpredictable and often debilitating nosebleeds. After 12 weeks, patients who received the 40-mg dose of VAD044 experienced “clinically meaningful” reductions in the frequency of their nosebleeds, a secondary endpoint of the trial, Vaderis said in an Aug. 27 release.
The release was light on any actual data, but the Swiss company did say that regression of HHT-associated vascular lesions was also observed.
Patients in the phase 1 trial either received the 40-mg dose, a 30-mg dose or placebo. The primary endpoint of the study was safety, and the data showed that VAD044 was similar to placebo when it came to the frequency and severity of off-target adverse events (AEs).
On-target AEs associated with inhibiting the AKT pathway—which helps cells survive and grow in response to extracellular signals—were mostly mild, transient and resolved, the company said.
Some of the patients have since been enrolled in a 12-month open-label extension, where they are receiving a 40-mg daily dose of VAD044. Interim six-month data from 27 of these patients “continue to show favorable safety and tolerability profiles with further improvements” in nosebleeds, Vaderis said.
CEO Nicholas Benedict said the company is already “interacting with major health authorities to plan the pivotal phase of development for VAD044 in HHT.”
“The excitement surrounding the results of the initial 12-week double-blind part of this trial is amplified by the continued improvements experienced by patients through six months,” Benedict added.
HHT is the second most common inherited bleeding disorder in the world and has been linked to severe disease burden, reduced life expectancy and a reduced quality of life. Despite this health impact, there are no approved treatments for the condition, according to Vaderis, which described VAD044 as “the first novel therapy intended specifically for the treatment of HHT.”
The company is also lining up the therapy to test in breast and prostate cancers, according to Vaderis’ website.
“We … already see that after six months of continuous treatment with VAD044 patients experience further improvements in all [nose bleeding] endpoints compared to those seen at 12 weeks,” Hans-Jurgen Mager, M.D., Ph.D., head of the Netherlands Reference Centre for HHT and the study’s co-primary investigator, said in a statement.
“It seems that VAD044 has not yet reached its peak effect on HHT disease activity at 12 weeks, and patients continue to improve over time without paying an unexpected price in terms of safety or tolerability,” Mager added.
Academic centers in the U.S. are currently 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 been shown to inhibit the PI3K/Akt signaling pathway.
Novartis has a more direct link to Vaderis, with the biotech having been set up in 2019 by two veterans of the Swiss Big Pharma, including Benedict himself.