Category: Clinical

Month: 17 Oct 2017

Issue: not yet available

Complement C3 inhibitor (APL-2) meets primary end-point in Phase II clinical trial to treat geographic atrophy

A complement 3 (C3) inhibitor (APL-2) has shown significant results in the experimental treatment of geographic atrophy.   In the Phase II multi-center, randomized, single-masked, sham-controlled study, 246 patients were enrolled across 40 clinical sites in the USA, Australia and New Zealand. Patients received 5 mg APL-2/100 µL, administered via intravitreal injection, either monthly or every other month for 12 months. Eyes were evaluated for geographic atrophy (GA) by fundus autofluorescence photographs (FAF) and the primary efficacy endpoint was the change in square root GA lesion size from baseline at month 12. According to the sponsor of the study, APL-2, met its primary endpoint showing a 29% (p=0.008) reduction in the rate of GA lesion growth compared to sham.  In patients treated every other month, a 20% (p=0.067) reduction was observed. Additionally, in a post hoc analysis, the sponsor claimed that a greater effect was observed during the second six months of the study where a reduction in GA growth rate of 47% (p<0.001) was seen with monthly administration, and a reduction of 33% (p=0.01) was seen with every other month administration.

 

The complement cascade is an innate part of the immune defence system, consisting of over 30 serum proteins. In general, substances on the surface of microbes or other infectious agents can trigger the complement cascade, which then activates a series of biochemical steps leading to the lysis (or bursting) of invading cells. However, certain complement proteins may also help trigger inflammation. Several components of the complement cascade have been found in drusen deposits which led to the hypothesis that AMD may result from dysfunctional inflammation which incorporates inappropriate complement activation. A series of seminal papers over 12 years ago established an association between variants in complement genes and increased risk of AMD, findings which attracted significant attention in the search for a clinical target. The complement pathway contains three arms – classical, alternative and lectin – all of which converge on C3, potentially making the molecule a key therapeutic target.

 

While over half a dozen or more complement targeted therapies have reached clinical trial stage, the APL-2 candidate appears to have demonstrated one of the more potent effects. The reasoning for this may be due to the central position of C3 in the various pathways leading to a more efficacious clinical result. Commenting on the results, David Boyer, MD, of Retina-Vitreous Associates Medical Group, stated, “These results are very exciting for all people afflicted with dry AMD with geographic atrophy. It is currently an untreatable condition, and the reduction of the progression of atrophy in this trial offers new hope for vision maintenance for our patients.”

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Gearoid Tuohy

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by Dr. Gearóid Tuohy   Dear EURETINA Members,   A very warm welcome to the November 17th, 2017 edition of EURETINA’s web-based digital magazine, “EURETINA Brief”. EURETINA are delighted to continue our delivery of up-to-date summary briefs on a range of topics of interest to retinal clinicians, specialists and researchers across Europe. This resource is […]