The Role of the Immune System’s Classical Complement Pathway
The classical complement pathway is one of three activation pathways of the immune system and, when functioning properly, is a major contributor to the body’s defense mechanism in fighting infections and clearing of pathogens.
When overactivated, the classical complement pathway can lead to a cascade of reactions that can lead to disease, such as Huntington’s Disease. At the start of this classical complement cascade is a molecule called C1q, which is responsible for activating a powerful inflammatory cascade that can lead to tissue damage. By blocking C1q, we may help stop the start of complement-mediated diseases, like Huntington’s Disease.
The Role of C1q in Neurodegenerative Diseases
In the same way that bonsai trees need to be pruned to stay healthy, our nerve cells, called neurons, also need to be pruned to support healthy brain development. When functioning properly, C1q enables removal or ‘pruning’ of the under-utilized or unneeded connections, called synapses, between neurons. These synapses help send messages from the brain to the body. In Huntington’s Disease, it is thought that neurons become stressed due to the presence of mutant Huntingtin protein, which can lead to the overactivation of the classical complement pathway and leads to C1q inappropriately pruning the synapses between neurons, resulting in neuroinflammation, neuronal damage, and motor and cognitive decline.
Annexon Biosciences is Developing ANX005, an Investigational Therapy for the Treatment of Huntington’s Disease
- ANX005 is a type of investigational treatment called an antibody, which is made in a lab and administered into the vein through an infusion.
- ANX005 is designed to block C1q activity to reduce neuroinflammation and protect synapses.
Annexon Has Completed a Phase 2 Clinical Study in 23 Patients with Early Manifest Huntington’s Disease
- A Phase 2 clinical study is designed to show if a treatment is safe and effective and to determine the appropriate dose and dosing frequency of an investigational medicine before it is evaluated in more patients.
- In this Phase 2 study, all participants received the investigational study drug.
- ANX005 was generally safe and well tolerated. Safety refers to the type of side effects that a participant may experience, whereas tolerability refers to the degree to which the side effects of a study drug can be tolerated. In this study, most side effects were mild or moderate in intensity. No deaths were reported in the study.
- Some patients with high levels of complement activity, which were measured before receiving ANX005, experienced improvements in their disease, including improvements in function and motor and cognitive abilities.
- Several biological markers associated with neuroinflammation decreased. Biological markers are used to see how well the body responds to a treatment for a disease or condition.
Annexon is Sponsoring a New Phase 2/3 Placebo-Controlled Clinical Study in Patients with Huntington’s Disease – Planned to Begin in 2023
- Have a clinical diagnosis of Huntington’s Disease
- Have a CAP score greater than 400
- Maintain the ability to self-care and maintain core activities of daily living
A Phase 2/3 clinical study is a significant step in the drug development process to determine if an investigational treatment is safe and effective. If the outcome is positive, the data collected during the clinical study may be submitted to regulatory agencies, such as the U.S. Food and Drug Administration, for approval and commercialization, making the drug available to the patients for whom the investigational therapy was designed to benefit.
A placebo-controlled trial is a study in which there are two groups of patients. One group of patients receives the active investigational treatment and the other group of patients receives the placebo. Everything else in the study is held the same between the two groups, so that any difference in outcome can be attributed to the active investigational treatment.
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