NEWTON, Mass. — Inflammasome Therapeutics announced positive six-month Phase 2 results for K8, an investigational treatment for geographic atrophy, showing slower lesion growth and a visual-acuity benefit compared with control eyes.
In the 0.7-milligram dose group, the mean rate of geographic atrophy growth was 54% lower than in the pooled control group over six months. The result was statistically significant under a slope analysis preferred by the U.S. Food and Drug Administration.
A prespecified analysis of patients with extrafoveal lesions also showed an adjusted four-letter advantage in best-corrected visual acuity for K8-treated eyes compared with control eyes.
Geographic atrophy is an advanced form of age-related macular degeneration that affects an estimated eight million people worldwide, including about 1.5 million in the United States and 2.5 million in Europe.
K8, also known as kamuvudine-8, is a dual inflammasome inhibitor delivered through a bioerodible, sustained-release intravitreal implant administered once every three months.
Inflammasome Therapeutics said all three K8 dose groups slowed the mean rate of geographic atrophy growth compared with pooled controls. The company noted that comparisons with approved treatments were based on separate studies rather than head-to-head trials.
“Clearing the high bar of 50% in slowing lesion growth and preserving or improving visual function suggests that K8 not only stops retinal cells from dying but also improves the function of distressed cells by reducing inflammation. The statistical significance of K8’s lesion-growth reduction fulfills the promise of earlier studies, which predicted that a drug with strong efficacy could demonstrate a statistically significant effect in GA with 30 patients. The dual benefit of K8 on structure and function should now be confirmed in Phase 3 studies,” said Jayakrishna Ambati, MD, Director of the Center for Advanced Vision Science and DuPont Guerry, III Professor of Ophthalmology at the University of Virginia and Founder of Inflammasome Therapeutics.
The multicenter U.S. study enrolled 30 participants with geographic atrophy in both eyes across nine clinical centers. The worse-seeing eye received a K8 implant, while the other eye remained untreated.
Researchers evaluated doses of 0.3 milligrams, 0.7 milligrams and 1.05 milligrams administered at the beginning of the study and again after three months. Imaging was evaluated by masked readers at an independent center.
No safety signals of concern were identified through six months. There were no drug-related serious adverse events, dose-limiting toxicities or cases of endophthalmitis, intraocular inflammation, neovascular age-related macular degeneration, retinal vasculitis or optic neuropathy.
“We have a real chance for a breakthrough here. The unmet need in GA — still the main cause of visual-acuity loss in macular degeneration — is huge. A signal for both a lower lesion-growth rate and a visual-acuity benefit reflects the direction the retina community has been seeking. These results warrant rigorous confirmation in Phase 3,” said Anat Loewenstein, MD, MHA, Professor of Ophthalmology and Vice President at Tel Aviv Medical Center.
Inflammasome Therapeutics said it plans to begin a global Phase 3 pivotal program evaluating K8 in geographic atrophy.
“These initial data in a clean, fellow-eye controlled trial appear quite promising. If the anatomic benefit is replicated in Phase 3, that would be highly differentiated. Stable or improved vision vs loss in the control eyes is notable, and repeat dosing every 3-4 months would be a welcomed advance. Overall, these substantive findings support moving efficiently into a pivotal program,” said Charles C. Wykoff, MD, PhD, Retina Specialist and Director of Research at Retina Consultants of Texas.
