Paul Hahn, MD: A Cross-Trial Comparison of Pegcetacoplan and Avacincaptad Pegol

New results from a cross-trial anchored matching-adjusted indirect comparison (MAIC) in patients with geographic atrophy (GA) suggest a greater reduction in GA lesion growth with monthly pegcetacoplan compared to avacincaptad pegol at month 12.

The analysis, presented at the American Society of Retina Specialists (ASRS) 41st Annual Meeting, was performed in the absence of a head-to-head trial, to gain a better understanding of the relative efficacy between the 2 therapies.

“The best thing to do would be a head-to-head clinical trial comparing 1 drug versus another, but it is very difficult to do and most likely won’t be done,” Paul Hahn, MD, PhD, NJ Retina, told HCPLive at ASRS 2023. “Instead, there is the MAIC approach, a well-validated approach used in ophthalmology and other fields. It tries to match the inclusion and exclusion criteria between 2 different trials and then balances those matched populations to have a similar group between 2 different trials and then you can compare the results.”

Individual patient data from the phase 3 OAKS and DERBY trials of monthly 15 mg pegcetacoplan versus sham and aggregate data from the phase 3 GATHER2 trial of 2 mg avacincaptad pegol versus sham were included in the analysis. The investigative team applied GATHER2 inclusion and exclusion criteria to individual patient data from OAKS and DERBY in order to select a similar subpopulation with non-subfoveal GA, best-corrected visual acuity (BCVA) ≤20/25, and without fellow eye choroidal neovascularization (CNV).

The analysis used propensity score weighting to balance key baseline variables selected a priori, including age, GA laterality, lesion focality, BCVA, low-luminance BCVA, and GA lesion size. Moreover, the change in GA lesion area from baseline to month 12 was separately compared between OAKS and GATHER2 and between DERBY and GATHER2 using MAIC. Results were then combined using meta-analysis; a secondary analysis compared efficacy in patients treated with every-other-month 15 mg pegcetacoplan versus monthly 2 mg avacincaptad pegol.

A total of 103 patients from OAKS (61 pegcetacoplan; 42 sham) and 102 patients from DERBY (49 pegcetacoplan; 53 sham) meeting inclusion criteria from GATHER2, and 447 patients from GATHER2 (225 avacincaptad pegol; 222 sham) were included in the analysis.

For OAKS versus GATHER2, the adjusted difference for change in GA lesion size between pegcetacoplan and avacincaptad pegol after matching was –0.716 mm2 (95% CI, –1.385 to –0.046; P <.05), a 37.0% statistically significant greater reduction in GA lesion growth for pegcetacoplan.

For DERBY versus GATHER2, the adjusted difference for change in GA lesion size between pegcetacoplan and avacincaptad pegol after matching was –0.234 mm2 (95% CI, –1.354 to 0.885; P = .68), a 12.1% numerically greater reduction in GA lesion growth for pegcetacoplan. The analysis showed the pooled effect for pegcetacoplan versus avacincaptad pegol was –0.589 mm2 (95% CI, –1.164 to –0.014; P <.05), a 30.4% statistically significant greater reduction in change in GA lesion growth with pegcetacoplan. Further analysis of less frequent dosing of every-other-month pegcetacoplan versus monthly avacincaptad pegol demonstrated comparable efficacy between the 2 groups.

“Our conclusion was that pegcetacoplan appears to have a better efficacy profile for nonsubfoveal GA when you’re comparing monthly dosing, and even every-other-month dosing, you now have a comparable efficacy profile to avacincaptad pegol monthly,” Hahn told HCPLive.

Relevant disclosures for Dr. Hahn include Adverum, Allergan, Apellis, Eyepoint, and Genentech.