Counter pressure device 100% effective in controlling drug reflux

June 1, 2005

Tucson, AZ—Use of a counter-pressure device (CPD) during the posterior juxtascleral administration of anecortave acetate for depot suspension (Retaane, Alcon Laboratories) effectively eliminates reflux to ensure consistent drug delivery, according to the results of a clinical pharmacokinetics study.

Tucson, AZ-Use of a counter-pressure device (CPD) during the posterior juxtascleral administration of anecortave acetate for depot suspension (Retaane, Alcon Laboratories) effectively eliminates reflux to ensure consistent drug delivery, according to the results of a clinical pharmacokinetics study.

The CPD is a gamma-irradiated, modified Wechsel sponge cut with a notch to allow apposition onto the conjunctiva. It is used during administration of anecortave acetate to apply pressure across the cannula and thereby prevent leakage of the drug back out through the conjunctival incision.

Efficacy of the CPD was tested in an open-label, two-center study of 44 eyes by investigators Henry L. Hudson, MD, Tucson, AZ, and Donald Roy, MD, Fresno, CA. Postadministration evaluations demonstrated that reflux was controlled in all eyes.

"This most recent pharmacokinetics study confirms that we can achieve reproducible delivery of anecortave acetate using the CPD," he said. "Based on theory and the observation that outcomes were superior in patients without reflux in the pivotal clinical trial, we expect posterior juxtascleral administration of anecortave acetate with use of the CPD should translate into greater efficacy and better visual outcomes."

The CPD was developed when the results of the pivotal trial for anecortave acetate showed the product was statistically equivalent in preserving vision compared with the active control treatment with verteporfin (Visudyne, Novartis/QLT PhotoTherapeutics) photodynamic therapy (PDT), but failed to meet the 7% non-inferiority criterion established by the FDA. That study randomly assigned 434 patients with predominantly classic lesions to anecortave acetate 15 mg or verteporfin PDT. Each treatment was administered with an appropriate sham of the other study agent. After 1 year, 45% of anecortave acetate-treated eyes maintained vision (<3 lines loss of ETDRS visual acuity) compared with 49% of eyes in the PDT control group.

Further analyses led to the identification of drug reflux at the time of administration as one of two controllable factors in the anecortave acetate group that might have negatively influenced outcomes. The second confounder was re-treatment administered later than the protocol-specified time of around 180 days.

"Reflux occurred in about half of the eyes in the anecortave acetate group, and with incomplete delivery to the target tissue, the treatment should not be expected to achieve the maximum possible therapeutic effect. In fact, reanalysis of the pivotal trial data shows 50% of eyes in which reflux did not occur maintained vision compared with only 39% of those with reflux," Dr. Hudson said.

"Based on knowledge of the pharmacokinetics of this modality, an eye that is re-treated after 180 days may have a period when it is not covered by therapy, and that may allow for reactivation of the choroidal neovascularization (CNV). Among eyes that both had no reflux and received re-treatment within the protocol-defined window, the outcomes with anecortave acetate get even better, with a 57% rate of maintaining vision. That outcome fulfills the 7% non-inferiority criteria of the study design," he added.

The CPD pharmacokinetics study enrolled patients with any form of exudative age-related macular degeneration. Eyes with predominantly classic CNV also received verteporfin PDT.

The CPD trial is a 1-year study and patients are receiving a second injection of anecortave acetate after 6 months. Preliminary efficacy data from the 6-month visit are expected to be presented in July at the annual meeting of the American Society of Retina Surgeons.

Dr. Hudson noted that this is the third pharmacokinetics study he has been involved in. Two previous studies evaluated anecortave acetate 15 mg and 30 mg.

"Together, these studies constitute a large body of treatment data for 85 patients enrolled with all types of CNV," Dr. Hudson said.