K8 Shows Greater GA Growth Reduction Over Time

Phase 2 Study Reports Reduced GA Growth With Investigational K8

Overview

At the 2026 AAO meeting, Liangbo Shen, MD, reported phase 2 findings for investigational kamuvudine K8 in geographic atrophy (GA). In the 30-participant, 6-month study, the 0.7-mg cohort had a 54% lower mean GA growth rate than untreated fellow eyes in the primary analysis; a piecewise analysis found reductions of 43% in months 0–3 and 70% in months 3–6. A prespecified nonsubfoveal GA subgroup showed a 4-letter BCVA advantage, but the study was not powered to assess visual function.

Background

GA is an advanced form of age-related macular degeneration, and approved intravitreal therapies target the complement pathway. K8 is an investigational inflammasome inhibitor designed to retain inflammasome inhibition while eliminating antiviral activity and mitochondrial toxicity associated with its original drug class. The source describes current complement therapies as having modest effects on lesion growth and no significant BCVA benefit in pivotal trials, as characterized by Dr. Shen. K8 is being evaluated as an approach targeting an alternative inflammatory pathway.

Data Highlights

Measure	Finding
Study design	Phase 2, multicenter US study; 30 participants with bilateral GA at 9 centers; 6 months
Dosing	Intravitreal implant at baseline and month 3; 0.3 mg, 0.7 mg, or 1.05 mg, with 10 treated eyes per dose cohort
Primary analysis, 0.7 mg	54% lower mean GA growth rate versus pooled untreated fellow-eye controls
Piecewise analysis, 0.7 mg	43% reduction in months 0–3; 70% in months 3–6; overall reduction 56% (P=.0084)
Participants with slower progression	25 of 30 had slower GA progression in the treated eye than in the fellow control eye
Nonsubfoveal GA subgroup	Covariate-adjusted 4-letter BCVA advantage for treated eyes among 14 treated and 16 control eyes (P=.004); study not powered for functional outcomes
Safety through month 6	No drug-related serious adverse events or dose-limiting toxicities reported; no observed endophthalmitis, intraocular inflammation, neovascular AMD, retinal vasculitis, or optic neuropathy

Key Findings

The study compared each participant’s treated, worse-seeing eye with the untreated fellow eye; the primary endpoint was mean GA lesion growth rate assessed by masked readers at an independent reading center.
In the primary analysis, the 0.7-mg dose reduced GA growth rate by 54% versus control eyes. The 0.7-mg and 1.05-mg cohorts had statistically significant reductions, while the 0.3-mg cohort showed a numerical trend favoring treatment.
In the 0.7-mg piecewise analysis, the reported reduction was greater during months 3–6 than during months 0–3; Dr. Shen said a longer and larger study was needed to further demonstrate the increasing effect.
In the prespecified nonsubfoveal GA subgroup, covariate-adjusted BCVA favored K8 by 4 letters (P=.004); investigators cautioned that the study was not powered to evaluate functional outcomes and that larger studies are needed to validate this finding.
No drug-related serious adverse events or dose-limiting toxicities were reported through month 6. Dr. Shen cautioned that the small study population limits conclusions about uncommon adverse events.
Related reporting described the same phase 2 study as showing a 54% lower mean GA growth rate in the 0.7-mg cohort over 6 months and noted that enrollment comprised 30 patients at 9 US centers.

Clinical Implications

Dr. Shen said Inflammasome Therapeutics is planning a global phase 3 pivotal trial to further evaluate K8 in GA. He noted that the phase 2 study was not powered to evaluate functional outcomes and that a larger study is needed to validate the BCVA finding. The small study population also limits conclusions about uncommon adverse events.

Conclusion

In this 6-month phase 2 study, the primary analysis reported a 54% lower mean GA growth rate with K8 0.7 mg versus untreated fellow-eye controls. A separate piecewise analysis reported reductions of 43% in months 0–3 and 70% in months 3–6, with an overall reduction of 56% (P=.0084). Dr. Shen said a longer and larger study is needed to further demonstrate the increasing effect.