An investigational vaccine designed to lower LDL cholesterol is part of a Phase 1 clinical trial of VXX-401 for the treatment of hypercholesterolemia being conducted by Cape Canaveral, FL-based Vaxxinity, Inc. Photo courtesy of Vaxxinity, Inc.
March 24, 2023 — Vaxxinity, Inc., a Cape Canaveral, FL-based company pioneering the development of a new class of immunotherapeutic vaccines, has announced that the first subjects have been dosed in a randomized, double-blind, placebo-controlled Phase 1 clinical trial of VXX-401. The focus of the study is an investigational vaccine designed to lower low-density lipoprotein (LDL) cholesterol, a known factor contributing to heart disease, by targeting proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9). Heart disease remains the leading cause of death globally, claiming over 18 million lives per year, despite the existence of approved treatments that lower LDL.
The multicenter Phase 1 dose-escalation trial aims to enroll 48 subjects aged 18 to 75 years, with LDL cholesterol between 2.59 and 4.89 mmol/L, according to details released by the company. The objectives of the trial are to evaluate safety, tolerability and immunogenicity (as measured by serum anti-PCSK9 antibody titers), noted the update, which reported that pharmacodynamics of the immune response will be measured by LDL cholesterol levels, an established model of PCSK9 inhibition in hypercholesterolemia in "A Study to Investigate the Safety, Tolerability, Immunogenicity, and Pharmacodynamics of VXX-401 Compared With Placebo in Adult Participants."
Vaxxinity presented pre-clinical data at the American College of Cardiology/World Congress of Cardiology Annual Scientific Session, ACC.23/WCC, in early March. In so doing, it demonstrated that VXX-401 induced robust anti-PCSK9 antibodies and durable LDL cholesterol lowering without affecting high-density lipoprotein (HDL) cholesterol levels, indicating that VXX-401 has the potential to be a safe and effective LDL lowering therapy. Data in non-human primate studies show that VXX-401 was well tolerated and provided durable and significant LDL reduction of 30% to 50% change from baseline. The data also demonstrate VXX-401’s immunogenicity: purified antibodies from immunized animals bound to human PCSK9 with high affinity, and exhibited a dose-dependent functional inhibition of PCSK9 in vitro. Additionally, Peripheral Blood Mononuclear Cells (PBMCs) collected prior to immunization did not release cytokines upon stimulation with various components of the vaccine, whereas PBMCs collected after immunization released IFN-γ and IL-4 upon stimulation with the full peptide immunogen or the T Helper peptide, but not upon stimulation with the PCSK9 epitope peptide, suggesting that VXX-401 may safely overcome immune tolerance.
In a statement announcing the status of the clinical trial, the company reported that VXX-401 was designed using Vaxxinity’s proprietary synthetic peptide vaccine platform and 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. VXX-401 is designed to induce robust, long-acting antibodies against PCSK9 in order to lower LDL cholesterol.
“This is an exciting milestone for VXX-401 and Vaxxinity in our pursuit to vaccinate the world against heart disease with a preventative option that is convenient and accessible, addressing an unmet need to combat the leading global cause of death,” said Mei Mei Hu, JD, Chief Executive Officer of Vaxxinity. Hu added, “PCSK9 antibody therapies are well-tolerated and effective, but huge unmet patient need remains. In order to solve the problem of heart disease, the world needs a scalable, accessible technology that can reach the hundreds of millions, if not billions of people at risk. With an LDL-lowering vaccine we can potentially offer an option that’s cost-effective, safe, convenient, long-acting, and deployable.”
“We’re excited to get this first-in-human trial of VXX-401 started. The concept of a vaccine for cholesterol could be a game-changer in cardiovascular health due to its potentially very broad reach and impact on human health,” said Professor Stephen Nicholls of Monash University and Victorian Heart Hospital in Clayton, Australia. “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. VXX-401 has the potential to extend the use of PCSK9 inhibition to the full population who could benefit.”
For more information: www.vaxxinity.com
June 11, 2025 
