Annexon Targets Guillain-Barre and Inflammatory Diseases with New Antibody

Annexon Biosciences is poised to unveil Phase III trial results for its lead program targeting Guillain-Barre syndrome (GBS) in the upcoming quarter. The company is also exploring other inflammatory diseases with its antibody, ANX005, which inhibits a protein complex known as C1q within the classical complement pathway, part of the innate immune system.

GBS is a rare autoimmune disease, impacting about 12,000 individuals in the U.S. and Europe annually. It paralyzes peripheral nerves in the limbs, severely affecting patients' mobility. Current treatments, such as intravenous immunoglobulin (IVIg) and plasmapheresis, provide only temporary relief. IVIg, sourced from human blood, can lead to severe adverse events like thromboembolic events upon repeated administration. Plasmapheresis, which removes antibodies from plasma and eases inflammation, involves risks such as bleeding and infections from catheter use.

ANX005 presents a novel approach. It targets the classical complement pathway, allowing the alternative and lectin pathways to remain functional, potentially leading to reduced immunosuppression compared to IVIg. This mechanism enables the immune system to continue combating pathogens while inhibiting unwanted inflammation.

In earlier Phase Ib trials, ANX005 was used alongside IVIg in an open-label treatment arm for GBS patients. The current Phase III trials will compare two doses of ANX005 against a placebo, with primary endpoints focusing on the GBS Disability Score at eight weeks and adverse effects over six months. These trials are critical for assessing the safety and efficacy of ANX005 in treating GBS, providing hope in a field where other treatments like corticosteroids and interferon-beta 1a have fallen short.

Annexon is also investigating ANX005's potential in other inflammatory diseases. In Huntington’s disease, a progressive movement disorder linked to the classical complement pathway, ANX005 has shown promise in Phase IIa trials. The safety profile of ANX005, with adverse effects primarily limited to infusion-site reactions upon the first dose, appears more favorable compared to IVIg, which can cause systemic side effects such as chills, fever, and muscle pain.

Further, ANX005 is being explored for amyotrophic lateral sclerosis (ALS), targeting disease progression. These promising developments signal an exciting future for Annexon as it continues to innovate in the treatment of inflammation-driven diseases.