Retaane no better than PDT in phase 3 trial

HÜNENBERG, Switzerland — Anecortave acetate failed to show superiority to photodynamic therapy in preserving vision loss from exudative age-related macular degeneration, according to an initial analysis of phase 3 study data. Non-inferiority to PDT was the primary endpoint of the comparative trial, according to a news release from Alcon, the drug’s developer.

At 1 year follow-up, 45% of patients treated with Retaane (anecortave acetate for depot suspension, Alcon) and 49% of patients treated with PDT using Visudyne (verteporfin for injection, QLT/Novartis) maintained vision, defined as a loss of less than three lines of logMAR visual acuity, according to Alcon.

No clinically relevant safety issues were observed in the trial, the company noted.

“Although anecortave acetate did not meet the primary non-inferiority endpoint of the clinical study, these overall results indicate that the two therapies are not statistically different from each other,” the Alcon press release said.

The company said it believes the results were negatively affected by two controllable factors, the drug treatment interval and drug reflux. Reflux is leakage of some of the drug from the conjunctival incision during or immediately following application, the company said.

Alcon said it has initiated procedural changes to control drug reflux in future trials. A counter-pressure device (CPD) is being evaluated for the control of reflux. Preclinical models have suggested efficacy of the CPD, and a clinical pharmacokinetic study has been started to evaluate it, the company said. The company is incorporating the device into all anecortave acetate studies worldwide.

“Controlling drug reflux may provide a moderate improvement in patient outcomes. But it is too early in the analysis to provide all the details,” said Gerald D. Cagle, PhD, senior vice president of research and development for Alcon, in an investor conference call this morning.

The company still plans to submit a new drug application to the FDA for anecortave acetate by the end of the year, which is expected to include results of the pharmacokinetic study.

“We believe the FDA will consider the entire package in making a risk-to-benefit assessment of Retaane,” Dr. Cagle said.

Following news of the trial results, shares of Alcon’s stock fell as much as 15% on Thursday, Reuters reported.

Market analysts predicted that it is unlikely Alcon will gain regulatory approval for Retaane before 2006, according to CBS MarketWatch. Analysts also noted that Eyetech Pharmaceuticals could have its anti-AMD drug Macugen (pegaptanib sodium) on the market by the middle of 2005. Macugen received a positive opinion from an FDA advisory panel in August.