Apellis releases 24-month results of phase 3 studies for GA treatment

Apellis Pharmaceuticals announced Wednesday top-line, 24-month data of the phase 3 DERBY and OAKS studies analyzing intravitreal pegcetacoplan for geography atrophy (GA) secondary to age-related macular degeneration (AMD).

The latest results found that pegcetacoplan—an investigational, targeted C2 therapy—exhibited increased effects over time.

A pre-specified analysis of GA lesion growth over 24 months showed both monthly and very-other-month injections of pegcetacoplan resulted in a clinically meaningful reduction of GA lesion growth from baseline compared to sham (with all p-values nominal), according to a company news release.

DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030

OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002

Additionally, between months 18 and 24, the effect of pegcetacoplan treatment accelerated when compared to previous 6-month periods, with significant reduction of GA lesion growth versus sham, the release stated.

These increased effects were caused by a greater slowing of lesion growth by pecetacoplan and not by an increase in lesion growth rate in the sham group, which was reported as highly consistent over each of the 4 6-month intervals (1.0+/-0.05 mm2).

DERBY: 36% monthly, p<0.0001; 29% EOM, p=0.0002

OAKS: 24% monthly, p=0.0080; 25% EOM, p=0.0007

Findings also included a reduction of GA lesion growth in patients extrafoveal lesions (28% monthly; 28% EOM) that was comparable to the reduction in patients with foveal lesions (34% monthly; 28% EOM) in the combined studies between months 18-24, the company reported.

As expected, no clinically meaningful difference was determined between pegcetacoplan and sham in the key secondary endpoints measuring visual function in 24 months.

According to Jeffrey Eisele, PhD, Apellis’s chief development officer, the data further reinforces the breakthrough potential of pegcetacoplan.

“With a US PDUFA date in November and [a European Union] submission planned later this year, we are committed to bringing pegcetacoplan to patients as quickly as possible,” he stated in the release.

Both studies found GA lesion growth to be correlated with loss of visual function over longer periods of time. Visual function outcomes were believed to be a result of limitations of the endpoints when used for GA as well as the relatively early assessment timeframe, the released stated.

Further, patients will be treated with pegcetacoplan in the GALE extension study for an additional 3 years.

The company also reported the following results:

Pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety data to date and longer-term exposure to intravitreal injections. No cases of endophthalmitis were reported between months 18 and 24.

Over 24 months, the rate of infectious endophthalmitis was 0.034% per injection and the rate of intraocular inflammation was 0.24% per injection, which continue to be generally in line with reported rates in studies of other intravitreal therapies.

No events of occlusive vasculitis or retinitis were observed over 24 months, and no serious adverse events of ischemic optic neuropathy were reported between months 18 and 24. The combined rate of new-onset exudations at month 24 was 11.9%, 6.7%, and 3.1% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively.

Results of the 24-month data will be featured in the marketing authorization application Apellis intends to submit to the European Medicines Agency by the end of 2022.

In the US, a marketing application is under priority review with a Prescription Drug User Fee Act target action date of Nov. 26, 2022.