Inflammasome Therapeutics announced positive phase 2 results for its investigational drug K8 (kamuvudine-8) in geographic atrophy (GA), with no safety signals of concern identified over 6 months. K8 was associated with a significantly slower disease progression and visual-acuity advantage, the company said in a press release.
K8 is an investigational dual-inflammasome inhibitor delivered through a bioerodible sustained-release intravitreal implant designed for administration every 3 months.
In the 0.7 mg cohort, the mean rate of GA growth was 54% lower than in the pooled group of control eyes over 6 months (2-sided p=0.016, FDA-preferred slope analysis). A prespecified analysis of eyes with extrafoveal lesions also showed a covariate-adjusted 4.0 ETDRS letter mean advantage for the entire K8-treated group in best-corrected visual acuity compared with all control eyes over 6 months (2-sided p=0.004).
According to the company, all 3 K8-dose cohorts in this trial slowed the mean rate of GA growth compared with the pooled control group over 6 months.
The primary endpoint was analyzed using the FDA-preferred linear mixed-effects slope model accounting for treatment, baseline lesion area, time, interactions between these factors, and inter-eye correlation.
Visual function was assessed in a prespecified analysis of eyes with extrafoveal lesions. The reported mean 4.0-ETDRS letter difference in best-corrected visual acuity between the treated and control groups over the 6-month analysis period was adjusted for lesion growth rate, lesion focality, and low-luminance deficit, the company said in the press release.
The multicenter US study enrolled 30 participants with bilateral GA across 9 clinical centers, representing 60 eyes. The worse-seeing eye received a K8 implant, while the fellow eye remained untreated. Three doses were evaluated: 0.3 mg, 0.7 mg, and 1.05 mg. Participants received K8 at baseline and a repeat injection at Month 3.
Each dose cohort was compared with the pooled control group. The statistical model accounted for baseline lesion area, treatment dose, time, interactions between these terms, as well as the correlation between eyes from the same participant. GA imaging was assessed by masked readers at an independent reading center.
According to the company, no safety signals of concern were identified across the 30-patient study through Month 6. There were no drug-related serious adverse events and no dose-limiting toxicities. In addition, there were no events of endophthalmitis, intraocular inflammation, neovascular age-related macular degeneration, retinal vasculitis, or optic neuropathy.
K8 was administered using a 24-gauge in-office injector and is designed to provide sustained drug delivery over 3 months. The product requires no refrigeration or cold-chain storage, and is supplied in a preloaded injector.
Inflammasome Therapeutics said it plans to initiate a global phase 3 pivotal program to evaluate K8 in GA and will seek regulatory input as it prepares the planned global phase 3 program.
These findings were presented at the American Society of Retina Specialists Annual Meeting in Montreal by Jayakrishna Ambati, MD, founder of Inflammasome Therapeutics, and director of the Center for Advanced Vision Science, and DuPont Guerry III, professor of ophthalmology at the University of Virginia.
Dr. Ambati noted that the combination of reduced lesion growth and a visual-acuity signal together suggests K8 could be affecting both retinal-cell survival and function: "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."
He added that "the dual benefit of K8 on structure and function should now be confirmed in phase 3 studies."