Alzheimer's Disease and Therapeutic Antibodies

Alzheimer's Disease and Therapeutic Antibodies

• Amyloid precursor protein (APP) is found in neurons. Its function isn't fully understood but it plays roles in nerve cells.
• Normally, gamma secretase cleaves APP, creating non-toxic fragments.
• Mutations in APP can lead to altered cleavage by gamma secretase, producing toxic A-beta fragments.
• These toxic fragments aggregate outside nerve cells, forming plaques.
• Plaque buildup is toxic, causing neuronal death and abnormal brain function, leading to Alzheimer's disease.
• Treatments for Alzheimer's focus on reducing A-beta toxicity and plaque formation.

Treating A-beta Overproduction

• A-beta aggregates form plaques leading to Alzheimer's symptoms.
• Genetic manipulation to correct APP mutations is possible but viability is uncertain.
• Reducing APP production by degrading APP mRNA is a genetic approach, potentially using siRNA technology.
• Inhibiting enzymes that create A-beta (e.g., gamma secretase) is another approach.
• Increasing A-beta removal using antibodies that bind to A-beta and prevent aggregation is possible.

Therapeutic Antibodies in Alzheimer's

• Multiple A-beta/plaque-targeting therapeutic antibodies have been developed.
• Some have proven failures, some promising efficacy, and others are still under clinical studies.
• Lecanemab, developed by Biogen, reduced plaques and slowed cognitive decline and was approved in 2023.

Biosimilars

• Biosimilars are copycat versions of biological medicines.
• Unlike small-molecule generics, biologics are often made in living cells, so precise duplication isn't always achievable.
• Key difference between biosimilars and reference products - differences in binding sites, affinity, or other properties may exist even if the target is the same.
• Biosimilar manufacturing processes are not easily replicated.
• Biosimilars are similar (but not identical) to original biologics. Safety and efficacy must be proven before approval.
• First US biosimilar was in 2015. By 2022, 39 were approved, 22 launched.

Biosimilar Arrival Time

• Biosimilars typically arrive on the market about 20 years after the reference product.
• Data shows various arrival times for specific drugs and manufacturers.

Biosimilar Impact on Market Price

• Biosimilars are expected to significantly reduce drug costs (approx. 50% savings).
• The potential savings are greater than the savings provided by generic small molecule drugs.

Conclusion of Presentation and Summary

• Overview of therapeutic antibodies, polyclonal and monoclonal antibodies, vaccination, and antibody structure.
• Discussion of biosimilars and their market impact.
• A list of key takeaways regarding antibodies, biosimilars and impacts.