Anecortave acetate found safe, effective in AMD

April 15, 2006

New York?Anecortave acetate (Retaane 15 mg suspension, Alcon Laboratories) seems to be safe and effective for the treatment of exudative age-related macular degeneration (AMD) compared with photodynamic therapy (PDT) with verteporfin for injection (Visudyne, Novartis Ophthal-mics/QLT Inc.).

New York-Anecortave acetate (Retaane 15 mg suspension, Alcon Laboratories) seems to be safe and effective for the treatment of exudative age-related macular degeneration (AMD) compared with photodynamic therapy (PDT) with verteporfin for injection (Visudyne, Novartis Ophthal-mics/QLT Inc.).

Clinical studies that evaluate combining anecortave acetate with other pharmacotherapies are needed to determine the drug's role in this arena, according to Jason S. Slakter, MD.

Although this drug is derived from a "steroid backbone," Dr. Slakter explained, "key chemical substitutions have rendered it devoid of glucocorticoid activity. It is not an anti-inflammatory drug, does not increase the IOP, and does not cause cataracts. Instead, anecortave acetate has become a potent anti-angiogenic agent."

Many steps are involved in the angiogenic cascade, and anecortave acetate is sufficiently potent to affect many of those steps.

"Many of the links in the chain that leads to angiogenesis can be broken by anecortave acetate to achieve a superior result," Dr. Slakter said. He is clinical professor of ophthalmology, NYU School of Medicine, New York.

Anecortave acetate is administered every 6 months outside the eye by a posterior juxtascleral depot route. Because of initial problems with reflux of the drug when it was delivered in this manner and to maximize the level of drug behind the eye, a training certification program is ongoing in all of the clinical studies in which the drug is used.

"A counterpressure device is used to minimize reflux and the delivery protocol has been modified," Dr. Slakter said.

He explained that the localization of anecortave acetate behind the eye can be visualized using the prototype Artemis high-resolution ultrasonography (UltraLink LLC), which was developed by D. Jackson Coleman, MD, from Cornell University.

"It allows us to see the localization of the drug in the sub-Tenon space on the scleral surface over the macular region before and after the administration of anecortave acetate and can continue to image it 3 and 6 weeks after depot administration," he explained.

The C-01-99 trial, a non-inferiority study with a primary efficacy analysis performed 12 months after the first administration of anecortave acetate, required administration of the drug every 6 months outside the eye. The results were compared at 12 and 24 months with those obtained using PDT with verteporfin administered every 3 months, according to the standard protocol. The study patients had predominantly classic choroidal neovascularization (CNV) secondary to AMD.

The 24-month results indicated that the follow-up was excellent, with 90% completing the 12-month examination and 84% the 24-month examination. The lesions treated in this study in both the PDT group and the anecortave acetate group were very small and of recent onset, according to Dr. Slakter. Most of the lesions had characteristics of retinal angiomatous proliferation that is now recognized as an aggressive form of CNV.

"At the 24-month end point, there was no statistical difference between the two drugs in the mean visual acuity. Clinically, at 12 and 24 months the mean visual acuity levels in the two groups differed by only three letters. Throughout the course of the study the mean visual acuity levels in the two groups did not vary by more than three and a half letters," Dr. Slakter reported.

Anecortave acetate exhibited a safety record that was similar to that of PDT. Dr. Slakter noted that at the 24-month follow-up examination there were no significant differences in ocular safety between the two treatment groups and there also were no differences in the non-ocular safety profile.

Results similar

"The results of the C-01-99 study suggest that the anecortave acetate suspension behaved in a clinically similar manner to verteporfin PDT in preserving vision at 12 and 24 months. Most importantly, the anecortave acetate suspension maintained an excellent safety profile. The data from this trial and others suggest the potential clinical benefits of anecortave acetate outweigh any potential risks of this therapy," Dr. Slakter commented.

Dr. Slakter suggested that anecortave acetate may play a substantial role in the treatment of AMD.