Inflammasome Therapeutics reported six-month Phase II results showing its investigational drug K8 slowed geographic atrophy lesion growth by more than half in the trial's mid-dose cohort, according to a press release issued by the Massachusetts-based company. The K8 geographic atrophy data, presented at the American Society of Retina Specialists meeting in Montreal, also showed a statistically significant visual-acuity advantage over control eyes — an endpoint neither of the two currently approved GA therapies met in their pivotal trials. For a disease with no cure and only modest treatment options, a signal of preserved vision alongside slower lesion growth addresses a key limitation of existing therapies and may warrant advancement into late-stage development.
Geographic atrophy is an advanced form of dry age-related macular degeneration marked by progressive death of retinal tissue, affecting an estimated eight million people worldwide. K8 (kamuvudine-8) is a dual inflammasome inhibitor delivered as a bioerodible, sustained-release intravitreal implant dosed once every three months; it is designed to block inflammasome activation triggered by multiple toxic drivers of GA — including complement, retrotransposons and oxidative stress — rather than a single upstream pathway. K8 remains fully investigational and has not been approved by the FDA or any other regulatory authority.
The multicenter Phase II trial enrolled 30 participants with bilateral GA across nine US centers — 60 eyes total, with the worse-seeing eye receiving a K8 implant and the fellow eye serving as an untreated control. Three doses (0.3 mg, 0.7 mg, 1.05 mg) were tested, administered at baseline and again at month three. In the 0.7 mg cohort, the mean rate of GA lesion growth was 54% lower than in the pooled control group over six months (p=0.016), using the FDA-preferred linear mixed-effects slope model. A prespecified analysis restricted to eyes with extrafoveal lesions — those with the greatest potential for vision preservation — showed a covariate-adjusted 4.0-letter mean BCVA advantage for K8-treated eyes versus controls (p=0.004); BCVA changes were positive at every visit in the K8 group and negative at every visit in controls.
No drug-related serious adverse events or dose-limiting toxicities were reported through month six, and there were no cases of endophthalmitis, intraocular inflammation, neovascular AMD, retinal vasculitis or optic neuropathy. The results extend an earlier readout from the same trial, which showed a 66% reduction in lesion growth at three months in an initial five-patient cohort — a result the company used to justify expanding enrollment to 60 eyes.
Two therapies are approved in the US for GA: Apellis Pharmaceuticals' Syfovre (pegcetacoplan), a complement C3 inhibitor cleared in February 2023, and Astellas' Izervay (avacincaptad pegol), a complement C5 inhibitor approved in August 2023. Both require monthly or near-monthly intravitreal injections and reduced GA lesion growth by roughly 13-14% versus control over their first six months of dosing, without demonstrating a visual-acuity benefit in Phase III testing. Neither has secured EMA approval, reportedly reflecting European regulators' emphasis on functional vision outcomes rather than anatomic lesion measures alone. Inflammasome Therapeutics frames the 54% growth reduction and paired BCVA signal as clearing "a high bar" relative to those benchmarks, though the comparison is cross-trial rather than head-to-head, and the underlying patient populations, endpoints and control designs differ.