Charles Wykoff, MD, PhD: Shifting the Treatment Paradigm with Pegcetacoplan for GA


A look into major takeaways on efficacy, safety and functional data from the DERBY and OAKS trials on pegcetacoplan.

The largest unmet need in retina care remains a treatment for geographic atrophy (GA), the advanced dry form of age-related macular degeneration (AMD).

The global Phase 3 DERBY and OAKS trials randomized patients with GA equally to two arms of active treatment and one arm of sham. The active treatment was 15 milligrams pegcetacoplan monthly or every-other-month.

Pegcetacoplan is an investigational, targeted C3 therapy for the treatment of GA secondary to AMD from Apellis Pharmaceuticals, Inc, with a potential FDA approval coming in late November of this year.

At the American Academy of Ophthalmology (AAO) 2022 Annual Meeting, Charles Wykoff, MD, PhD, Director of Clinical Research, Retina Consultants of Texas presented the two-year outcomes from DERBY and OAKS in a late-breaking session.

In an interview with HCPLive, Wykoff discussed the efficacy, safety and functional data from the trials. The observed treatment benefits with pegcetacoplan were similar between trials, with every-other-month dosing reducing GA lesion growth by 16 - 18% and every month dosing reducing it by 19 - 22%.

"Then, when you look at six month intervals over the two-year period, the key finding is that that growth reduction with treatment appears to be increasing over time," Wykoff said. "And there's some fascinating possible biological mechanisms that may explain that that deserve a lot more research and work."

Wykoff noted the most meaningful safety signal was the increased incidence of wet AMD development in eyes being treated with pegcetacoplan.

"The reason this is important is that this is also another cause of vision loss that we need to be aware of when we're treating these patients clinically, if and when this drug becomes available," he added.

Functional data were additionally reported, after being masked for two years. Wykoff noted these findings were twofold. All of the prespecified endpoints did not show a meaningful difference between the treated arms and the sham arms.

But, when using the microperimetry analysis to look in the perilesional zones, investigators observed a signal of functional benefit with treatment.

"This is a big deal for the field," Wykoff said. "I believe that's the first time that we're seeing a direct signal of a treatment benefit that slows progression and potentially preserved visual function in that retina that's being preserved."

On the ultimate treatment benefit of the medication, Wykoff noted that while it is real and ultimately clinically meaningful, he would love to be discussing the agent's ability to reverse GA growth and bring vision back.

"That's not what this medicine does, this medicine meaningfully decreases the rate of growth," he said. "But, this is going to be a complicated story. And it's a story that's going to take time to explain to patients what our goals of therapy are."

He added that patients should understand it will most likely be a lifelong therapy for most. The two-year data suggest patients will need to be treated consistently beyond this time period.

"It looks like with this medication, if and when it's available, there'll be more consistent dosing long term every month or every other month, not an insignificant treatment paradigm for patients," Wykoff said. "But, one that I think these patients are going to welcome in a space where there's nothing currently available."

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