Genentech's Macular Degeneration Candidate Flunks Phase III Study

September 8, 2017
By Mark Terry, BioSpace.com Breaking News Staff

South San Francisco – Genentech a Roche company, announced that its lampalizumab failed to meet its primary endpoint in a Phase III trial for geographic atrophy (GA) due to age-related macular degeneration (AMD).

Lampalizumab is being evaluated in two Phase III trials. In the first of the trial, Spectri, the drug didn’t reduce mean change in GA lesion area compared to “sham treatment” at 48 weeks. Because of the lack of results, dosing will be halted in patients until the data from the second Phase III trial are analyzed.

“Geographic atrophy is a progressive and irreversible disease that impairs vision, and there are currently no available treatments,” said Sandra Horning, Genentech’s chief medical officer and head of Global Product Development, in a statement. “While this result is disappointing, we will continue to evaluate results from Spectri to get a clearer understanding of the data as we await the results of our second Phase III study, Chroma, anticipated in November.”

The two trials have identical designs. They’re both double-masked, randomized, global studies looking at 10 mg doses of lampalizumab administered every four or six weeks by intravitreal injection compared to sham injections. The patients have geographic atrophy due to age-related macular degeneration. There are more than 1,800 people enrolled in the two studies in 275 sites in more than 20 countries.

GA is a progressive and irreversible type of age-related macular degeneration (AMD). It affects more than 5 million people globally. Visual problems associated with GA typically affect both eyes. They report visual problems with activities of daily living, including reading, driving, recognizing faces, and anything done in dim or low light. There are no approved therapies.

The symptoms of GA usually started when a patient can’t see one or more letters in a word while reading, or when looking at faces, part of the face isn’t seen. Once GA begins, the region of atrophy over several years tends to expand until central vision is gone. It doesn’t typically affect peripheral vision.

Lampalizumab is an antigen-binding fragment (Fab) of a humanized, monoclonal antibody directed against complement factor D (CFD). CFD is an enzyme involved in the activation and amplification of the alternative complement pathway (ACP), which is part of the immune system. Malfunctions of the ACP has been linked via genetic studies to AMD.

The primary endpoint was measured by fundus autofluorescence (FAF), which provides data about the size and type of GA lesions in the macula. The company did not report on secondary objectives, which will be evaluated at 96 weeks, and focused on lampalizumab’s effect on the patient’s visual function. The drug’s safety was consistent with previous trials and other intravitreal therapies.

This news is striking in how much it differs from earlier trials. In an 18-month trial of 129 AMD patients, researchers observed a 20 percent reduction in lesion area progression in patients on the drug. In addition, genome analysis of a subgroup of patients with complement D variants showed a 44 percent cut in GA area progression. As such, there was speculation the drug would be a viable treatment option for patients with secondary geographic atrophy.