Inflammasome Therapeutics has announced positive topline results from a clinical trial of its K8 implant for geographic atrophy (GA), a severe form of dry age-related macular degeneration (AMD). The trial, conducted at the University of Kentucky (NCT06164587), showed that a single injection of the K8 implant resulted in a substantial reduction in GA lesion growth after three months.
The study involved five patients with bilateral GA, each receiving a single K8 implant injection in one eye. Fundus autofluorescence (FAF) imaging, analyzed by an independent masked reading center, revealed a mean reduction of 66% in GA lesion growth in the treated eyes compared to the untreated contralateral eyes (p = 0.029). Furthermore, the lesions progressed at a slower rate in the K8-treated eyes across all five patients.
Safety and Tolerability
The K8 implant demonstrated a favorable safety profile, with no drug-related ocular or systemic serious adverse events reported. This positive safety data, combined with the efficacy results, has led to the expansion of the trial to include 30 patients (60 eyes). These patients will receive a second K8 injection at month 3 of the 6-month trial.
Mechanism of Action
K8 is a first-in-class dual inflammasome inhibitor designed to target multiple pathways involved in GA progression. GA, affecting approximately one million people in the US and over eight million worldwide, involves the accumulation of toxic substances in the eye, leading to inflammasome activation and subsequent macular cell atrophy. Unlike existing FDA-approved drugs that target a single substance in the complement pathway, K8 blocks inflammasome activation caused by multiple toxic substances, potentially offering a more comprehensive approach to treating GA.
Expert Commentary
"Natural history studies have shown that in bilateral GA patients the lesion growth rates in the two eyes are almost identical, with less than 5% difference between eyes. Therefore, a 66% reduction in K8-treated eyes compared to contralateral eyes of the same patients provides strong evidence of efficacy," said Jayakrishna Ambati, MD, co-founder of Inflammasome Therapeutics. He added, "K8 has a unique mechanism of action whereby it blocks the effects of complement activation as well as numerous other inflammatory pathways in GA, a multifactorial disease."
Paul Ashton, Ph.D., CEO and co-founder of Inflammasome Therapeutics, noted, "These initial clinical trial results are extremely encouraging...we believe that the statistical significance of the 66% reduction in lesion growth of 66% (p=0.029) compared to the untreated eyes seen with only 5 patients is indicative of the drug’s robust effect. Thus, K8 may present an opportunity to break through the efficacy ceiling observed with the approved anti-complement drugs in GA."
Ongoing and Future Development
The expanded trial will continue to evaluate the safety and efficacy of K8 injections administered every three months. The primary endpoints are safety and the difference in GA lesion growth between treated and untreated eyes. Inflammasome Therapeutics is also exploring the potential of Kamuvudines, the class of drugs to which K8 belongs, for treating neuro-inflammatory diseases such as ALS, Parkinson’s disease, and Alzheimer’s disease.
