Complement C3 inhibitor is a potential treatment for AMD

November 7, 2008

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.

A cyclic 13-amino acid peptide (POT-4, Potentia PharmaceuticalsInc.) is the first complement-binding therapy tested in humanswith wet age-related macular degeneration (AMD). PhilipRosenfeld, MD, PhD, of the Bascom Palmer Eye Institute,University of Miami Miller School of Medicine, presented resultsfrom the phase I Clinical Trial Assessment of Safety for POT-4(ASaP) that indicate the drug appears to be safe and welltolerated and released slowly from a deposit in the vitreouscavity.

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

"Complement inflammation appears to play an important role inAMD," he said. "[The drug] specifically inhibits C3 and by sodoing, all of the subsequent activated anaphylactic peptides thatare associated with complement and disease progression may beaffected."

In in vitro and in animal models, the peptide was not toxic incynomolgus monkeys after 500 intravitreal and intravenousinjections.

When injected into the vitreous cavity, the drug forms a gel-likedeposit that decreases in size over time, facilitating slowrelease of the therapy. Serum concentrations also have beendetected from 2 to 13 weeks after administration in monkeys.

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

Six cohorts with three patients each have been treated with from1 to 450 µm of the agent thus far.

"The vision has remained stable and increased in some cases withno serious decreases in vision," Dr. Rosenfeld said. "Onlyminimum or mild adverse events associated with the injection sitehave been seen. Interestingly, one day after the injection of the450-µm dose, there was a deposit in the intravitreal cavitythat was gone by day 15 and the drug was detected in theserum."

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