The Australian macular disease community has welcomed the latest clinical trial results for Apellis Pharmaceuticals’ intravitreal pegcetacoplan, fuelling hope that the first potential treatment for geographic atrophy (GA) is on the horizon.
On 24 August, Apellis announced top-line data at 24 months showing increased effects over time with its investigational therapy in the Phase 3 DERBY and OAKS studies in GA secondary to age-related macular degeneration (AMD).
In a pre-specified analysis of GA lesion growth over 24 months, the company reported that both monthly and every-other-month (EOM) pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham (all p-values are nominal):
- DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030
- OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002
Between months 18-24, the pegcetacoplan treatment effect accelerated compared to previous six-month periods, with robust reductions of GA lesion growth versus sham. The increased effects were driven by a greater slowing of lesion growth by pegcetacoplan and not by an increase in the lesion growth rate in the sham group, which was highly consistent over each of the four six-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
Additionally, the reduction of GA lesion growth in patients with extrafoveal lesions (28% monthly; 28% EOM) was comparable to the reduction in patients with foveal lesions (34% monthly; 28% EOM) in the combined studies between months 18-24.
“These trial results give patients hope that the first potential treatment for GA is on the horizon,” said Professor Robyn Guymer, who is a study investigator of the DERBY and OAKS trials, and deputy director of the Centre for Eye Research Australia and Professor of Surgery (Ophthalmology) at the University of Melbourne.
Dr Kathy Chapman, CEO of Macular Disease Foundation Australia (MDFA), said the loss of central vision through GA results in a significant burden for affected people, their families and society at large, including increased mental health issues, the loss of productivity and job reduction.
“The patient community welcomes these results and any future advances which may help to make a meaningful difference for patients.”
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system.
Consistent with expectations, Apellis also reported no clinically meaningful difference between pegcetacoplan and sham in the key secondary endpoints measuring visual function at 24 months.
Studies show that GA lesion growth is correlated with loss of visual function over longer periods of time. The visual function outcomes at 24 months are believed to be due to the limitations of the endpoints when used for GA and the relatively early assessment timeframe. Patients will be treated with pegcetacoplan in the GALE extension study for an additional three years.
“These data further reinforce the breakthrough potential of pegcetacoplan, with both monthly and every- other-month treatment demonstrating increased effects across a broad patient population over 24 months,” said Mr Jeffrey Eisele chief development officer at Apellis.
“With a US PDUFA date in November and an EU submission planned later this year, we are committed to bringing pegcetacoplan to patients as quickly as possible.”
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.
The results at 24 months will be included in the marketing authorization application that the company plans to submit to the European Medicines Agency by the end of this year. The US marketing application is under Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of 26 November 2022.
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