Session Title: Quick Fire Free Paper 5
Session Date/Time: Sunday 14/09/2014 | 11:00-13:00
Paper Time: 11:05
Venue: Boulevard B
First Author: : F.Holz GERMANY
Co Author(s): : S. Schmitz-Valckenberg B. Yaspan Z. Li E. Henry E. Strauss -0 -0
Genetic variations and complement hyperactivity are implicated in the pathogenesis of age-related macular degeneration (AMD). Lampalizumab (formerly identified as FCFD4514S and anti-factor D) is an antigen-binding fragment that targets complement factor D, a rate-limiting enzyme in the alternative complement pathway and potential therapeutic target for geographic atrophy (GA) secondary to AMD. The MAHALO Phase II study assessed the safety, tolerability and evidence of activity of lampalizumab in patients with GA.
The MAHALO phase II study was a prospective, multicenter, randomized, single-masked, sham-injection-controlled study conducted at clinical sites in the United States of America and Germany (NCT01229215, EudraCT number 2010-019183-36).
The MAHALO Phase II study enrolled 129 patients aged 60–89 years with GA secondary to AMD in the absence of choroidal neovascularization. Patients were randomized 2:1:2:1 to lampalizumab 10 mg or sham, administered monthly or every other month. The sham arms were pooled for the analyses. The primary endpoint was change in GA area from baseline to month 18 as assessed by confocal scanning laser ophthalmoscopy-fundus autofluorescence imaging. In an exploratory analysis, we also evaluated the relationship between established genetic polymorphisms associated with AMD and GA characteristics and lampalizumab treatment response.
One hundred twenty-three patients received at least 1 sham or lampalizumab treatment and had at least 1 post-baseline primary efficacy measurement (sham pooled, n=40; lampalizumab monthly, n=42; lampalizumab every other month, n=41), which satisfied pre-specified criteria for evaluation. A 20.4% reduction in GA progression was reported in the all-comer lampalizumab monthly arm relative to the pooled sham arm. This positive treatment effect was observed at month 6 through month 18. Furthermore, a 44% reduction in GA progression was observed in a subpopulation treated monthly with lampalizumab and positive for the complement factor I (CFI) biomarker; 57% of the collected samples in MAHALO were CFI biomarker-positive. Lampalizumab demonstrated an acceptable safety profile in the Phase II study; there were no deaths and no ocular or systemic serious adverse events suspected to be study drug-related.
MAHALO is the first study to show a positive treatment effect in reducing GA progression through complement inhibition. The positive effect observed following monthly lampalizumab treatment was further magnified in the CFI biomarker-defined subpopulation. Our data suggest that the CFI biomarker appears to be both prognostic for GA progression and predictive for lampalizumab treatment response.