Surgery Section - Conjunctival Incision with Posterior Juxtascleral Placement of Anecortave Acetate Depot Suspension

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Many new pharmacologic agents promoting angiostasis for the treatment of age-related macular degeneration are in development including Anecortave Acetate (Retaane®) for Depot Suspension. Anecortave Acetate is a synthetic cortisone that has been chemically modified into an angiostatic cortisene that inhibits the proteolysis required for vascular endothelial cell migration, thereby inhibiting ocular neovascularization. Anecortave Acetate is a slow-release depot suspension that may be delivered at six month intervals and allows for sustained delivery to the affected area near the macula when administered by the novel procedure of posterior juxtascleral (extrascleral) placement. Anecortave Acetate for Depot Suspension (Alcon Research, Ltd.) received an approvable letter from the U.S. Food and Drug Administration (FDA) in May 2005 for treatment of age-related macular degeneration but has not yet received final FDA approval.

In the conjunctival incision with posterior juxtascleral placement of the depot suspension procedure, after topical anesthesia, a 1.0-1.5 mm to 2-3mm incision into the superior temporal quadrant of the orbit is made 8 mm posterior to the limbus between the superior and lateral rectus muscle insertions. The incision is made down through the conjunctiva and Tenon’s capsule to reveal bare white sclera but not incise the sclera. A specially designed, blunt-tipped, curved, 56° cannula is then carefully inserted into the juxtascleral (episcleral) plane between the outer surface of the sclera and Tenon’s capsule and fed forward until the cannula tip is near the macula. Gentle pressure is applied around the inserted cannula during administration of the depot suspension and removal of the cannula to prevent reflux and a semipressure patch is applied.

Advantages to the posterior juxtascleral placement of a pharmacologic agent include reduced risk for retinal detachment, endophthalmitis and other safety issues associated with repeated intravitreal injections (a common route of administration for pharmaceutical agents in the treatment of ocular disorders).

Policy/Criteria

Conjunctival incision with posterior juxtascleral (extrascleral) placement of Anecortave Acetate Depot Suspension is considered investigational.

Scientific Background

The procedure of conjunctival incision with posterior juxtascleral placement of Anecortave Acetate Depot Suspension has been performed over 350 times in 128 patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD) in the Anecortave Acetate Clinical Study Group. (2-5) The Anecortave Acetate Clinical Study, a blinded, randomized controlled trial, was conducted at 18 clinical sites in the United States and the European Union, followed patients for two years and was completed in June 2003. Some patients in the study had this procedure performed several times in the same superior temporal quadrant including four times in 48 patients and at least two times in 81 patients. No serious clinically relevant treatment-related safety issues were reported from either the study medication (Anecortave Acetate) or the procedure for administration. The two most observed adverse events were cataracts and decreased visual acuity (=4 logMAR lines or =20 logMAR letters) which occurred in both study and placebo groups at similar rates. Cataracts occurred at 27% and 30% and decreased visual acuity occurred at 25% and 30% in the treatment and placebo groups respectively. These occurrences included study eyes, untreated eyes or both eyes and are commonly experienced in patients with ARMD. Other adverse events that were reported as mild and transient included ptosis, ocular pain, vision abnormalities (e.g., hazy vision, black spots, light flashes), subconjunctival hemorrhage and ocular pruritus.

In summary, conjunctival incision with posterior juxtascleral placement of Anecortave Acetate Depot Suspension or placebo appears to be technically feasible and clinically safe in this study of 128 patients. The adverse events reported were mostly mild and transient and are commonly experienced with ocular procedures.

An October 2005 TEC Special Report on the treatment of age-related macular degeneration supports the conclusions given above. (6) The special report noted that, although suggestive, the results of the Anecortave Acetate Clinical Study Group lack robustness. The trial was only partially blinded and censoring was substantial. No dose-effect was evident with 15 mg being superior to placebo and 30 mg being less efficacious. The analytical approach to missing data was suboptimal, and whether assumptions of repeated measures ANOVA were met (correlations equal over time) was unstated. Finally, adverse effects, even transient, were frequent among both treated and placebo groups.

Regillo and colleagues analyzed clinical safety data from 313 patients enrolled in the anecortave acetate studies. (7) With the exception of a nearly 10% retinal detachment rate with juxtascleral depot injections, anecortave acetate or vehicle, the authors reported this to be a safe and well-tolerated procedure. The Anecortave Acetate Clinical Study Group published results of a phase III noninferiority trial comparing anecortave acetate with photodynamic therapy. (8) Patients (n=530) were randomized to treatment either with anecortave acetate plus sham photodynamic therapy (n=263) or active photodynamic therapy plus placebo (n=267). Eighty-two percent of the subjects were available for the 12-month evaluation with similar drop-out rates in the two groups. The percentage of patients who lost more than three lines of letters was similar in the two groups (55% for anecortave acetate and 51% for photodynamic therapy). However, the confidence interval was greater than the seven percentage points specified by the regulatory agencies and this treatment did not meet statistical criteria for noninferiority. A Cochrane review of the Anecortave Acetate Clinical Study (AACS) described above concluded that, “anecortave acetate 15 mg may have a slight benefit in treating subfoveal CNV related to AMD. However, the data presented in the AACS are of low quality given the high attrition rate, inadequate sample size, lack of adjustment for multiple comparisons, and potential bias in the non-randomized re-treatment schedule.” (10) The author’s overall conclusion was that “given the small size and quality of the trials reported, there is little evidence to support the use of steroids in the treatment of neovascular AMD.” Clinical studies of anecortave acetate are in progress for the treatment of other conditions. (11) The available scientific evidence does not permit conclusions concerning the effect of this treatment on health outcomes.

In summary, this procedure is considered investigational because anecortave acetate has not yet received final FDA approval. In addition, it has not been demonstrated to be at least as safe and effective as currently available treatments and further studies on long-term health outcomes are needed. Clinical trials are in progress to evaluate dose (i.e., 15 versus 30 mg) and frequency of administration (i.e., every three versus six months), and to determine if administration of anecortave acetate in patients with dry age-related macular degeneration reduces the risk of developing choroidal neovascularization. (9)

References

1. BlueCross BlueShield Association, Medical Policy Reference Manual, Policy No. 9.03.16
2. Schmidt-Erfurth U, Michels S, Michels R, et al. Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Eur J Ophthalmol. 2005;15(4):482-5
3. Augustin AJ, D'Amico DJ, Mieler WF, et al. Safety of posterior juxtascleral depot administration of the angiostatic cortisene anecortave acetate for treatment of subfoveal choroidal neovascularization in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2005;243(1):9-12
4. D'Amico DJ, Goldberg MF, Hudson H, et al. Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration: twelve-month clinical outcomes. Ophthalmology. 2003;110(12):2372-83; discussion 2384-5
5. D'Amico DJ, Goldberg MF, Hudson H, et al. Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy. Retina. 2003;23(1):14-23
6. BlueCross and BlueShield Association Technology Evaluation Center Special Report:  Current and Evolving Strategies in the Treatment of Age-Related Macular Degeneration. Technology Evaluation Center. January 2006  (Verified 1/12/09)
7. Regillo CD, D'Amico DJ, Mieler WF et al. Clinical safety profile of posterior juxtascleral depot administration of anecortave acetate 15 mg suspension as primary therapy or adjunctive therapy with photodynamic therapy for treatment of wet age-related macular degeneration. Surg Ophthalmol 2007;52(Suppl 1):S70-8
8. Slakter JS, Bochow T, D’Amico DJ, et al. Anecortave acetate versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration. Ophthalmol 2006;113(1):3-13
9. Bakri SJ, Kaiser PK. Anecortave acetate. Expert Opin Investig Drugs 2006;15(2):163-9
10. Geltzer A, Turalba A, Vedula SS. Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration. Cochrane Database Syst Rev 2007; (4):CD005022
11. http://www.clinicaltrials.gov/ct2/results?term=anecortave+acetate (Verified 1/12/09)

Cross References

None

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