Early results from the Phase II FILLY trial of the complement factor 3 (C3) inhibitor APL-2 (Apellis Pharmaceuticals) have confirmed the role the complement pathway has in the progression of age-related macular degeneration and offers some hope for the treatment of geographic atrophy (GA). Going forward, investigators hope to duplicate these results in
Phase III trials, says principal investigator David Boyer, MD.

 “Until now many people have thought the complement pathway may play role in geographic atrophy, but because of results of the FILLY trial it seems like the complement system does indeed offer some ability to treat the patients to prevent progression of geographic atrophy,” says Dr. Boyer, of Retina-Vitreous Associates Medical Group in Los Angeles.

Geographic atrophy has confounded retina specialists because it remains a major cause of vision loss in patients with dry AMD and there is no Food and Drug Administration-approved treatment for it. Shortly after Apellis announced the FILLY trial results, Roche/Genentech disclosed that the Spectri trial, the first of two Phase III trials of lampalizumab for treatment of GA, failed to meet its primary endpoint, which was mean change in GA lesion area compared to sham treatment at one year.

The primary endpoint of FILLY was the change in GA lesion size from baseline to month 12 in the treatment group compared to sham. APL-2 was administered as an intravitreal injection in the study eye monthly or bimonthly for 12 months, followed by six months of monitoring after the end of treatment.

The early FILLY readout reported that monthly intravitreal injection of APL-2 showed a 29-percent reduction in the rate of GA lesion growth at 12 months compared to sham (p=0.008), and a 20-percent reduction with bimonthly administration (p=0.067).

A post-hoc analysis showed a greater effect during the second six months of the study: a reduction in the growth rate of GA lesions of 47 percent (p<0.001) with monthly administration, and a reduction of 33 percent  (p=0.01) with bimonthly administration.

Says Dr. Boyer, “It seems that the difference between the treatment and sham groups really separates at the six-month level, and if that continues to go in a similar direction at 18 months, then this is a very powerful drug that may be able to help us treat patients with geographic atrophy long term.”

Dr. Boyer notes that a number of studies are investigating the role the complement factor pathway in progress of AMD. “All point to the inflammatory mechanism or cascade as eventually causing activation and cell apoptosis, and continuing to progress the size of geographic atrophy lesions,” Dr. Boyer says.

Adverse events in the FILLY trial were similar to those reported with other intravitreal therapies, Dr. Boyer notes.

The Phase II FILLY data is still fresh. “Hopefully in the next several months we can obtain more information and get a more complete idea if there’s a certain genetic subtype that does better with this therapy,” he says. The lampalizumab phase 2 Mahalo trial had a subgroup that responded better to therapy than the overall trial cohort. “Right at the moment the genetics are being evaluated to see if there’s a genetic predisposition for a certain group of patients to do better,” he says.

One of the more intriguing findings of the FILLY trial, Dr. Boyer explains, involved patients who received ALP-2 either monthly or bimonthly and had wet AMD in one eye and dry AMD in the fellow eye. Many of those patients eventually developed choroidal neovascularization. “They had a higher rate than the sham group,” says Dr. Boyer, “and it was higher in the monthly than in the every-other-month treatment group, indicating that perhaps some degree of the transition from dry to wet is controlled by the complement pathway and blocking the complement pathway allows the patients to go on to develop wet AMD.”

However, this was not so much the  case in patients who had dry AMD with no wet AMD in the other eye. That will be further investigated in the forthcoming subanalysis of the FILLY data.

The FILLY trial involves 246 patients at 40 clinical sites, in the United States, Australia and New Zealand.

Investigational OCT Platform Eliminates Adaptive Optics

Researchers at MedUni Vienna have developed a new optical coherence tomography technique called Line Field-OCT that eliminates the use of adaptive optics to correct the occurring image defects in obtaining cellular resolution of the retina.

PhD student Laurin Ginner and Rainer Leitgeb of MedUni Vienna reported on the new LF-OCT technology in a study published last month in the journal Optica.1

"With our new method, we can make the corrections digitally without the need for expensive, hardware-based adaptive optics,” Mr. Ginner says. “Due to the line illumination used, very fast image rates are possible which are extremely important for these corrections. This allows us to correct image defects over the entire three-dimensional volume of the retina."

The line lighting works similar to a scanner  in that a light strip “scans” the eye. Individual photoreceptors, capillary blood vessels and individual nerve fibers can be resolved in the same receptacle. Furthermore, refocusing is possible, as are reorientation and digital post-processing of the obtained image data in order to provide highest resolution results for the diagnostics.  RS

1. Ginner L, Kumar A, Fechtig D, et al. Noniterative digital aberration correction for cellular resolution retinal optical coherence tomography in vivo. Optica. 2017;4:924-931.