Pipeline for dry AMD features diverse compounds
Investigational agents represent several strategies; complement inhibition shows most promise to date
Take-home message: A number of drugs are being investigated in clinical trials as treatment for slowing the growth of geographic atrophy that is secondary to age-related macular degeneration.
Miami—Though there are currently no treatments for geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and the development of several investigational agents was halted because of disappointing results, other promising drugs are continuing to move through the therapeutic pipeline.
“Treatments that are now in clinical trials aim to slow the growth of GA,” said Philip J. Rosenfeld, MD, PhD.
“They represent several different strategies,” said Dr. Rosenfeld, professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami.
Complement inhibition has progressed to a phase III clinical trial based on data from a phase II trial of one of these inhibitors—lampalizumab (Genentech)—which showed a signal that it may work, he noted.
Lampalizumab is an antigen-binding fragment from an antibody that blocks the complement 3/complement 5 (C3/C5) alternative pathway convertase. It is administered as an intravitreal injection and advanced into the phase II study, known as MAHALO, after demonstrating favorable safety in a phase I trial.
MAHALO evaluated lampalizumab administered monthly and every other month. The patients enrolled had bilateral GA with visual acuity ranging from 20/50 to 20/400. Results after 18 months showed treatment effect was statistically significant based on an aunconventional p-value cut-off of p = 0.2. However, in a genetic subset of patients carrying the complement factor I (CFI) at-risk allele in which GA appeared to growth faster, the rate of GA growth was reduced 44% by lampalizumab (p < 0.005).
The phase III lampalizumab study program is under way. The two intervention trials, Chroma and Spectri, plan to enroll 1872 patients with visual acuity of 20/100 or better; 60% of patients being entered will carry the CFI+ allele. Lampalizumab is being administered monthly or every 6 weeks.