Geographic atrophy

Arshad Khanani MD, MA

Two phase 3 clinical trials should help determine the efficacy of lampalizumab (Roche), a new category of drug being evaluated for the treatment of geographic atrophy, reported Arshad Khanani MD, MA at the WOC 2016 in Guadalajara, Mexico.

Lampalizumab, an antigen-binding fragment of a humanised monoclonal antibody directed against complement factor D, acts by blocking initiation and amplification of the alternative complement pathway. It is being evaluated in two phase 3 studies enrolling more than 1,872 patients at approximately 275 sites worldwide.

Two identically designed pivotal interventional trials, Chroma and Spectri, each plan to randomise 936 patients to intravitreal injection with lampalizumab or sham every four or every six weeks. Patients will have bilateral geographic atrophy without choroidal neovascularisation (CNV). Each treatment group will include complement factor I biomarker-positive (CFI+) and CFI- patients. Mean change in geographic atrophy lesion area from baseline at one year, measured by fundus autofluorescence, is the primary efficacy endpoint.

“At month 18 in the phase 2 Mahalo study, lampalizumab reduced geographic atrophy area progression versus sham by 20 per cent in the overall population, but by 44 per cent in CFI+ patients. The hypothesis that CFI is a biomarker for response is being confirmed in the current phase 3 programme,” said Dr Khanani, Clinical Assistant Professor, University of Nevada, Reno, USA.

VISUAL FUNCTION

The studies are also designed to assess visual function using parameters that may be better than best corrected visual acuity (BCVA) for demonstrating the functional impact of geographic atrophy. They include low luminance VA, reading speed, the NEI Visual Function Questionnaire-25, and the Functional Reading Independence index (FRI, available online at: www.mapi-trust.org).

“We know that patients with geographic atrophy present with complaints about vision, but their BCVA can still be good. The lampalizumab clinical trials are assessing visual function outcome measures for which changes may be identified before there is deterioration of BCVA. A letter supporting the FRI was recently published by the European Medicines Agency,” he told EuroTimes.

In addition to the phase 3 trials, two additional trials, Proxima A and Proxima B, are ongoing observational studies designed to contribute to the understanding of the anatomic and visual function changes in a broad population of patients with geographic atrophy. “It is hoped that the Proxima studies will significantly advance our knowledge of geographic atrophy natural history,” Dr Khanani said.

Arshad Khanani: arshad.khanani@gmail.com