Sunday, October 17, 2010

Complement inhibition may be the future of dry AMD therapy

CHICAGO — Ongoing clinical trials exploring the use of complement inhibitors for treating nonexudative age-related macular degeneration offer promise for a disease state that has long been considered difficult to treat.

A number of recent studies have implicated the complement immune system in AMD. However, nonexudative AMD remains a "uniquely human disease," and, therefore, no animal model exists in which to prove potential therapeutic strategies, Philip J. Rosenfeld, MD, PhD, said here are Retina Subspecialty day preceding the joint meeting of the American Academy of Ophthalmology and the Middle East Africa Council of Ophthalmology.

As a result, Dr. Rosenfeld said, human trials will prove important in determining whether complement inhibition is of any real clinical benefit.

Several such trials are already underway. Alcon is currently investigating its POT-4 (AL-78898A) anti-C3 cyclic peptide in human trials. There is some evidence that POT-4 may also affect VEGF expression in the retina, Dr. Rosenfeld said.

Separately, Genetech/Roche has an anti-factor D (FCFD4514S) that inhibits the C3 and C5 alternative pathway convertases. Phase 1 studies have been successfully completed with that agent, Dr. Rosenfeld said.

Two separate C5 inhibitors are being studied: Eculizumab/Sollris (Alexion) and ARC1905, an anti-C5 aptamer (Ophthotech).

"One of the advantages is that while you block the downstream activated species, you preserve the more proximal species that are important for the clearance of bacteria, particularly the encapsulated organisms," Dr. Rosenfeld said.
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