In March 2023, Vaxxinity announced that the first subjects of a Phase I trial had been dosed. The trial of VXX-401 will evaluate the safety, tolerability, and immunogenicity of the investigational vaccine designed to lower low-density lipoprotein (LDL) cholesterol. This is a known contributing factor of heart disease, which remains the “leading cause of death globally”. 

LDL and heart disease 

Vaxxinity states that heart disease claims “over 18 million lives per year”. LDL cholesterol, also known as ‘bad’ cholesterol, is a leading factor in heart disease incidence. Although there are approved treatments to lower LDL, it continues to contribute to deaths.  

Enter VXX-401 

The investigational vaccine by Vaxxinity is designed to lower LDL levels by targeting proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9). Designed using Vaxxinity’s proprietary synthetic peptide vaccine platform, it is being developed for the treatment of hypercholesterolemia. The platform is designed to “harness the immune system to convert the body into its own natural ‘drug factory’, stimulating the production of antibodies”.  

The vaccine is being tested in a multi-centre Phase I dose-escalation trial that aims to enrol 48 subjects between the ages of 18 and 75 years with LDL cholesterol between 2.59 and 4.89 mmol/L.  

CEO of Vaxxinity, Mei Mei Hu, described this progress as an “exciting milestone” in the pursuit to “vaccinate the world against heart disease”. This goal includes an intention to keep the vaccine “convenient and accessible” in order to address an “unmet need”.  

“With an LDL-lowering vaccine we can potentially offer an option that’s cost-effective, safe, convenient, long-acting, and deployable.” 

Hu believes that the solution to the “problem of heart disease” will be a “scalable, accessible technology” that reaches the “hundreds of millions, if not billions of people at risk”. Professor Stephen Nicholls of Monash University and Victorian Heart Hospital in Australia is “excited” to get the “first-in-human trial” underway.  

Professor Nicholls suggests that the “concept of a vaccine for cholesterol” could be a “game-changer in cardiovascular health”.  

“Targeting PCSK9 with a monoclonal antibody is a proven and effective approach for lowering cholesterol and reducing the risk of heart attack and stroke. Despite the availability of statins and the approval of PCSK9-targeting medicines, there is still a need for new therapies.” 

Previous data 

Data from non-human primate studies demonstrate that VXX-401 was “well tolerated” and “provided durable and significant LDL reduction of 30% to 50% change from baseline”. They also prove strong immunogenicity and suggest that VXX-401 “may safely overcome immune tolerance”. 

We look forward to hearing more from Vaxxinity’s Mei Mei Hu at the World Vaccine Congress in Washington next month! Join us by getting tickets here.