Pharmacological options for AMD increasing

Chicago-A number of compounds are either available or under investigation to treat wet age-related macular degeneration (AMD), offering some hope to patients and clinicians, said Michael J. Tolentino, MD, of Winter Haven, FL.

“This is an exciting time for our patients with exudative wet AMD,” Dr. Tolentino said. The goal of AMD treatment is to stop growth of new blood vessels and vascular leakage by hindering the effects of vascular endothelial growth factor (VEGF). This can be done before VEGF binds to the receptor, preventing it from kicking off a cascade of detrimental events. Alternatively, intervention can occur after VEGF has triggered the cascade, by stopping its effects downstream.

Protein agonists that block VEGF after it is produced include pegaptanib sodium (Macugen, OSI/Eyetech/Pfizer), bevacizumab (Avastin, Genentech), ranibizumab (Lucentis, Genentech), and VEGF Trap (Regeneron Pharmaceuticals Inc.).

“Macugen is approved and Lucentis is in phase III trials. Avastin is being used off-label at this time, and VEGF Trap is starting a phase II clinical trial,” Dr. Tolentino said.

At least two agents are under investigation that stop VEGF before it binds to the receptor or before it’s made, using a method called RNA interference (RNAi).

“You get no VEGF, no new vessels, no leakage, and you stop the bleeding,” Dr. Tolentino said.

Investigational compounds using this approach include Cand5 and Sirna-27. A phase 1 trial of Cand5 has been completed and a phase II trial is enrolling. A phase 1 trial of Sirna-27 is also complete, and a phase II study will begin early next year.

Both drugs are currently administered intravitreally, but that could change.

“The big promise of Sirna is that it is so potent in such small quantities that you can probably get it as a drop,” Dr. Tolentino said.

Several other agents are also being looked at for their value in treating patients with AMD, including anecortave acetate (Retaane, Alcon Laboratories), squalamine lactate (Evizon, Genaera), Ad-PEDF, and PTK inhibitors.

“In summary, we have a lot of anti-VEGF therapies here,” Dr. Tolentino said. He is co-founder and director of clinical research for Acuity Pharmaceuticals, the company conducting clinical trials of Cand5.