#AAO22: In bid for first FDA nod in geographic atrophy, Apellis claims another first in eye disease field

CHICAGO — Eight weeks before patients and industry find out if the FDA approves the first treatment for geographic atrophy, an advanced form of age-related macular degeneration, the biotech behind the drug is out with some new data on a secondary endpoint.

In what study investigator Charles Wykoff called the “first direct evidence of function preservation by slowing GA growth” in an investigational treatment, Apellis Pharmaceuticals’ drug pegcetacoplan led to less loss of retinal sensitivity versus sham over 24 months.

The results come from one of two Phase III studies, OAKS, of the drug in patients with GA. The secondary endpoint was not observed in the other Phase III submitted as part of the drug approval application because of the logistics required to observe microperimetry, Wykoff told Endpoints News ahead of the data reveal at the American Academy of Ophthalmology annual meeting in the Windy City.

The reasoning is twofold: Many clinical trial sites around the world don’t use microperimetry frequently and it’s also a strain on patients — they have to assess whether they can see 68 individual spots and at different light thresholds, said the director of research at Retina Consultants of Texas.

Here are the actual data: For the 178 patients who received the pegcetacoplan injection every month, they had a nominal p-value of 0.0650. The result was more pronounced in the 184 patients who received the rejection every other month, with a p-value of 0.0202. The effects increased over time and were better than the sham group, which comprised 182 patients.

The effects were better than sham, but not statistically significant. Apellis, in its press release, claimed that’s because of the swath of retina area that was assessed, “which included areas that were farther away from the GA lesion and thus not at high risk of losing function due to GA lesion growth.”

Charles Wykoff

While the difference wasn’t significant, Wykoff described the results as “important to the entire field” because ophthalmologists have believed for years that slowing the growth of GA lesions (the primary endpoint that the drug beat sham on in both late-stage studies) leads to the preservation of function of vision.

“There’s never been an example of showing a treatment benefit” prior to Friday’s data, he said.

On the primary endpoint, Apellis previously reported the drug reduced the growth of GA lesions anywhere from 12% to 22% over 18 months (depending on trial and dosing interval) across the two Phase III studies. In a follow-up last month, the biotech reported the reductions were even greater at 24 months, ranging from 24% to 36%.

Those results are clinically meaningful, Wykoff said, but the “magnitude is not what anybody wants to see.” He’d love to see 80% to 90% reduction in growth, he said, noting how the GA leads to blindness in many patients.

“We see these patients every day and these patients are very dysfunctional,” he said.

If approved for GA, Wykoff said the drug would “fill a nice niche,” citing the paucity of an approved treatment for a condition that impacts about five million people globally: “That has been needed for years.”

The drug, to some analysts’ and Wykoff’s personal surprise, is not being reviewed by the FDA’s advisory committee ahead of decision day. The agency approved systemic pegcetacoplan, marketed as Empaveli, for patients with paroxysmal nocturnal hemoglobinuria in May 2021. In GA, pegcetacoplan was studied via intravitreal injection.

With no adcomm scheduled, Wykoff believes it “signifies a high likelihood of approval.” He said he personally finds it “fascinating that the percentage of new approvals with an adcomm has declined steadily from the early 2000s.”

It will likely be a patient-by-patient case whether they get the injection monthly or every other month if greenlit, Wykoff said. Efficacy was “slightly better” for the monthly dosing, but that dosing schedule might be a challenge for some patients.

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