A cyclic 13-amino acid peptide (POT-4, Potentia Pharmaceuticals Inc.) is the first complement-binding therapy tested in humans with wet age-related macular degeneration (AMD). Philip Rosenfeld, MD, PhD, of the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, presented results from the phase I Clinical Trial Assessment of Safety for POT-4 (ASaP) that indicate the drug appears to be safe and well tolerated and released slowly from a deposit in the vitreous cavity.

The complement system has been receiving much attention in the past few years because of its strong genetic association with AMD and potential as a treatment target.

"Complement inflammation appears to play an important role in AMD," he said. "[The drug] specifically inhibits C3 and by so doing, all of the subsequent activated anaphylactic peptides that are associated with complement and disease progression may be affected."

In in vitro and in animal models, the peptide was not toxic in cynomolgus monkeys after 500 intravitreal and intravenous injections.

When injected into the vitreous cavity, the drug forms a gel-like deposit that decreases in size over time, facilitating slow release of the therapy. Serum concentrations also have been detected from 2 to 13 weeks after administration in monkeys.

The ASaP trial (a prospective, open-label, ongoing investigation of 27 patients) is being conducted at six sites. Patients receive one injection ranging from 1 to 1,050 µm.

Six cohorts with three patients each have been treated with from 1 to 450 µm of the agent thus far.

"The vision has remained stable and increased in some cases with no serious decreases in vision," Dr. Rosenfeld said. "Only minimum or mild adverse events associated with the injection site have been seen. Interestingly, one day after the injection of the 450-µm dose, there was a deposit in the intravitreal cavity that was gone by day 15 and the drug was detected in the serum."

After studying the 1,050-µm injection, the hope is to move into a phase II study, he said.