Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Avacincaptad pegol (e.g., Izervay)

Description:

Avacincaptad pegol (e.g., Izervay) is a pegylated RNA aptamer, which functions as a chemical antibody against complement C5, and inhibits the cleavage of complement C5 into its fragments (C5a and C5b). As such, the involvement of Avacincaptad pegol in the inhibition of the complement cascade slows down the progression of geographic atrophy (GA) secondary to AMD.

It is the second drug to be approved for GA, following pegcetacoplan (e.g., Syfovre), which was approved in February 2023. Approximately 11 million individuals in the United States have AMD, about 1 million of whom have GA. Prevalence for GA in the US is an estimated 0.81% of the population, with up to 3.5% of individuals.

Regulatory Status

Avacincaptad pegol (e.g., Izervay) was approved by the U.S. Food and Drug Administration (FDA) on August 4, 2023, for the treatment of GA, secondary to age-related degeneration (AMD).

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective Date April 2024

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Avancincaptad pegol for any indication or circumstance, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, avancincaptad pegol for any indication or circumstance, is considered investigational.

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

The approval of avacincaptad pegol (e.g., Izervay) was based on results from the Phase 3 GATHER1 and GATHER2 studies, which evaluated the safety and efficacy of avacincaptad pegol compared with sham treatment. Over 12 months, the primary analysis of each trial showed a statistically significant reduction in the rate of GA lesion growth in patients treated with avacincaptad pegol, with a 35% reduction in GATHER1 and 18% reduction in GATHER2. Data indicated a reduction in the rate of GA lesion growth of 0.10 mm/year (P <0.01) in GATHER1, and 0.05 mm/year (P <0.01) in GATHER2, in patients treated with avacincaptad pegol compared with patients receiving sham treatment.

The manufacturer has suggested that the disparate results may be based on the lower percentage of U.S. patients in GATHER2 (about 40%, versus 75% in GATHER1). Patients in the United States in GATHER2 had a 13% smaller lesion size compared to the rest of the population, which, according to the manufacturer, may indicate an earlier stage of disease. Researchers have previously hypothesized that avacincaptad pegol may be more effective in earlier stages of disease, based on post-hoc analyses of GATHER1 data.

Results of GATHER1 after 18 months of treatment have been separately published and reveal a 32.2% observed reduction in GA lesion growth rate in the group administered avacincaptad pegol 2 mg monthly compared with that in the group receiving sham.

In GATHER2, patients in the avacincaptad pegol 2 mg group were re-randomized at Month 12 to either continue avacincaptad pegol 2 mg every month or change to avacincaptad pegol 2 mg every other month (EOM) for Months 12 through 23. Patients initially randomized to sham continued on monthly sham treatment. The estimated completion date for the trial was July 2023; however, results for this part of the trial have not been shared by the manufacturer as of the time of this publication.

In GATHER1, there was no difference in the mean change in best-corrected visual acuity (BCVA) or low-luminance (LL)-BCVA from baseline to Month 12 compared with sham. Although change in BCVA was included as a secondary endpoint, the study authors noted that changes were not expected, based on historical reports, and the trial was not designed to demonstrate statistical significance.

In UpToDate in the “Geographic Atrophy subsection of Age-related macular degeneration,” (Vavvas, 2024) summarized the following concerning the use of pegcetacoplan and avacincaptad: “In 2023, the FDA approved the first two drugs aimed at this disease (intravitreal injection of pegcetocoplan and intravitreal injection of avacincaptad-pegol based on surrogate endpoint trial results that demonstrated a calculated reduction in lesion size. However, approval of these drug has been controversial due to lack of demonstration of functional benefit and significant side effects. Early after pegcetacoplan approval, reports of rare but serious vasculitis events with significant vision loss were reported by the American Society of Retina Specialists. Due to lack of demonstration of functional benefit to any subgroup of patients, and the associated risks of vision loss, we do not endorse the use of these injections.”

In a study of rationale and outcomes of randomized controlled trial results, Spaide and Vavvas (2023) evaluated the outcome of autofluorescence loss, and functional vision tests. Their results demonstrated that Pegcetacoplan 2 mg showed statistically significant reduction in expansion of the area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase two trial. Nearly 40% of patients recruited for the monthly arm did not complete the treatment. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies as compared with untreated controls. Data released at 24 months follow-up showed statistically significant reduction in the area of autofluorescence-detected atrophy in both studies compared with sham. Patients did not show functional difference in best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in two randomized pivotal studies and showed a statistically significant reduction in the expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in the best-corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization.

CPT/HCPCS:

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.