Apellis Eyes Progress For Lead AMD Product

Apellis Pharmaceuticals' lead product APL-2 for geographic atrophy, a progressed form of age-related macular degeneration, has met its primary endpoint in a Phase II trial with the company planning to begin Phase III trials in 2018.

Apellis Pharmaceuticals Inc., a company focused on autoimmune and inflammatory diseases, has reported that APL-2, its complement C3 inhibitor in development for geographic atrophy (GA) linked to age-related macular degeneration (AMD), has met its primary endpoint in a Phase II trial (FILLY). The company now plans to use recently raised funds to initiate a Phase III trial in late 2018, in addition to progressing other pipeline products.

Apellis was founded in 2009 and closed a $60m Series E preferred stock financing earlier this month. Having licensed its technology from the University of Pennsylvania, the company believes that APL-2, which is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer, can control GA and late-stage AMD by binding to and blocking C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). This is a major protein of the complement system, a branch of the immune system, with a key role in autoimmune and inflammatory diseases.

AMD itself is a disorder of the macular, the central part of the retina, and can progress into GA, eventually resulting in irreversible loss of vision. There are currently no approved therapies for this advanced form of AMD. Apellis estimates that there are a million GA patients in the US alone.

Study Details

The primary endpoint for the FILLY trial, a 246-patient sham-controlled study, was to assess the change in GA lesion size from baseline to month 12 in comparison to sham. A 29% reduction in the rate of the lesion growth was observed, in comparison to sham, at 12 months when APL-2 was administered monthly through intravitreal injection (p=0.008). For administration every other month, there was a non-significant 20% reduction (p=0.067).

A post hoc analysis showed that a greater effect was seen during the second six months of the study, with a reduction in growth rate of 47% (p<0.001) for monthly administration and a 33% (p=0.01) for administration every other month.

The most frequently reported adverse events were associated with the injection procedure. A higher incidence of exudative AMD was observed in the treatment groups, predominantly in subjects with a history of exudative AMD in the fellow eye, and was managed with the administration of standard-of-care therapies, Apellis said.

Analysts from Biomedtracker described the results from the FILLY study as "encouraging".

Competition

Apellis is not the only company focusing on the complement system's role in autoimmune diseases with Roche's lampalizumab and Ophthotech Corp.'s Zimura (avacincaptad pegol) also in development, however they are both targeting another complement factor, C5.

Lampalizumab is being studied in two pivotal Phase III trials (CHROMA and SPECTRI) and top-line results are expected next month. (Also see "Critical Clinical Trial Updates Expected in 3Q" - Scrip, 7 Jul, 2017.)

BMT analysts noted that, "Lampalizumab’s Phase II results showed only a 20% slowing in the growth of GA lesions at 18 months compared to the 29% reported here at 12 months (both comparisons were relative to placebo). Like APL-2, lampalizumab did not show a statistically significant response with every other month dosing."

Ophthotec started a pivotal Phase II/III study with Zimura for GA in 2016, but recently revealed that it had maintained a limited number of trial sites for this study and would reassess its strategy after results from a competitor, which Biomedtracker assumes is lampalizumab.

In addition to GA, Apellis is also assessing APL-2 in two clinical trials for systemic administration in paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired blood disorder. Interim data from these trials have so far been positive in previously untreated patients and patients treated with the current approved therapy, Alexion Pharmaceuticals Inc.'s Soliris (eculizumab). (Also see "Alexion’s Soliris Slips Up In Pivotal PROTECT Kidney Transplant Study" - Scrip, 23 Dec, 2016.) Phase III trials for APL-2 in PNH are expected to begin soon.