Nathan Steinle, MD: Long-Term Efficacy of Pegcetacoplan in GALE Extension Study

Nathan Steinle, MD

Credit: California Retina Consultants

New findings from the GALE long-term extension study indicate the increasing treatment effects of pegcetacoplan injection (SYFOVRE®) over 30 months in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

The research, presented at the American Society of Retina Specialists (ASRS) 41st Annual Meeting, showed that pegcetacoplan injection reduced nonsubfoveal GA lesion growth by up to 45% between months 24 to 30, compared to projected sham.

“This therapy continues to work as patients get it over time and it continues to work at an exponential rate as patients continue to get it over time,” presenting investigator Nathan Steinle, MD, California Retina Consultants, told HCPLive at ASRS 2023. “Early in the trials, we saw a slowing of GA progression. Then, in the middle parts of the trial, we saw increased slowing of rates of progression. Then, by the final 6 months, we see continued slowing of progression to GA in patients who receive pegcetacoplan.”

Pegcetacoplan injection is the first, and currently only, treatment for GA secondary to AMD approved by the US Food and Drug Administration (FDA). The phase 3, open-label, extension GALE study (n = 792) aimed to evaluate the long-term efficacy and safety of pegcetacoplan injection in patients with GA. To do so, the investigative team evaluated the long-term incidence and severity of ocular and systemic TEAEs as well as the change in the total areas of GA lesions, as measured by fundus autofluorescence.

More than 80% of patients who completed the phase 3 OAKS and DERBY studies entered the GALE extension study, as well as 10 patients previously enrolled in the phase 1b study of pegcetacoplan. Those included in the 30-month GALE lesion growth reduction analyses were in the pegcetacoplan treatment arms through Month 24 in OAKS and DERBY, remaining on the same regimen in GALE.

Those treated with sham in OAK and DERBY were eligible to transition to pegcetacoplan treatment in GALE after month 24. The study used a projected sham arm to estimate the growth of GA lesions without treatment between months 24 and 30. It was estimated as the average 6-month mean rate of change in the OAKS and DERBY sham arms through month 24.

Upon analysis, results from GALE suggest pegcetacoplan demonstrated robust and increasing effects through 30 months with both monthly and every-other-month treatment. Pegcetacoplan was shown to reduce GA lesion growth with both monthly (39%; P <.0001) and every-other-month (32%; P <.0001) treatment between month 24 and month 30, compared to the projected sham arm (all P-values normal).

The analysis also showed pegcetacoplan reduced nonsubfoveal GA lesion growth with monthly (45%; P <.0001) and every-other-month (33%; P = .0023) treatment between months 24 and 30, compared to the projected sham arm.

Safety analyses in GALE revealed consistent results with previously reported phase 3 data. The rate of exudative AMD was consistent with previous phase 3 data, with 7.5 and 7.2 events in the monthly arm and 3.9 and 3.6 events in the every-other-month arm per 100 patient-years at month 24 and month 30, respectively.

A total of 0 non-serious adverse events of ischemic optic neuropathy were reported in either treatment group between month 24 and month 30, while 1 serious adverse event of ischemic optic neuropathy was reported in the monthly group. Analyses showed no cases of endophthalmitis between months 24 and 30.

Meanwhile, data showed the rate of intraocular inflammation was 0.26% per injection among all patients treated with pegcetacoplan in the phase 3 program. There were no events of retinal vasculitis observed in the clinical trial program, after ≥23,000 injections of pegcetacoplan to date, according to the investigative team.

For more insight into the analysis, watch the full interview with Dr. Steinle here:

Relevant disclosures for Dr. Steinle include Apellis, Genentech, Novartis, and Regeneron.