Details

Autor(en) / Beteiligte

• Vroom, Madeline M.
• Lu, Hanxin
• Lewis, Maggie
• Thibodeaux, Brett A.
• Brooks, Jeanne K.
• Longo, Matthew S.
• Ramos, Martina M.
• Sahni, Jaya
• Wiggins, Jonathan
• Boyd, Justin D.
• Wang, Shixia
• Ding, Shuang
• Hellerstein, Michael
• Ryan, Valorie
• Powchik, Peter
• Dodart, Jean-Cosme

Titel

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys

Ist Teil von

• Journal of lipid research, 2024-02, Vol.65 (2), p.100497-100497, Article 100497

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a “high-risk” patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD. VXX-401 is designed to trigger a safe humoral immune response against PCSK9, resulting in the production of endogenous antibodies and a subsequent 30–40% reduction in blood LDL-C. In this article, VXX-401 demonstrates robust immunogenicity and sustained serum LDL-C-lowering effects in nonhuman primates. In addition, antibodies induced by VXX-401 bind to human PCSK9 with high affinity and block the inhibitory effect of PCSK9 on LDL-C uptake in a hepatic cell model. A repeat-dose toxicity study conducted in nonhuman primates under good laboratory practices toxicity indicated a suitable safety and tolerability profile, with injection site reactions being the main findings. As a promising safe and effective LDL-C-lowering therapy, VXX-401 may represent a broadly accessible and convenient option to treat hypercholesterolemia and prevent ASCVD.