Key Takeaways

  • K8 achieved a 54% reduction in geographic atrophy lesion growth at the 0.7-mg dose over 6 months and demonstrated a statistically significant 4.0-letter BCVA advantage in a prespecified subgroup analysis
  • The phase 2 fellow-eye controlled trial enrolled 30 patients and reported no major safety concerns through 6 months, with no drug-related serious adverse events or intraocular inflammation
  • Inflammasome Therapeutics plans to advance K8 into a global phase 3 pivotal program 

Inflammasome Therapeutics has reported positive topline results from a phase 2 clinical trial evaluating its investigational therapy K8 (kamuvudine-8) for geographic atrophy (GA), demonstrating statistically significant reductions in lesion growth alongside an improvement in visual function over 6 months.

The findings are being presented by Jayakrishna Ambati, MD, at the American Society of Retina Specialists Annual Meeting in Montreal. 

According to the company, the 0.7-mg dose cohort achieved a 54% reduction in the mean rate of GA lesion growth compared with the pooled control group over 6 months using the FDA-preferred linear mixed-effects slope analysis (two-sided P=0.016). In a prespecified subgroup analysis of eyes with extrafoveal lesions, treatment with K8 was associated with a covariate-adjusted 4.0-letter advantage in best-corrected visual acuity (BCVA) versus control eyes (two-sided P=0.004).

The company noted that cross-trial comparisons should be interpreted cautiously but stated that the lesion-growth reduction observed with K8 exceeded the approximately 13% to 14% reductions reported during the first 6 months of phase 3 studies for the two currently approved GA therapies. Those studies did not report a visual-acuity benefit.

K8 is an investigational dual inflammasome inhibitor delivered as a bioerodible sustained-release intravitreal implant administered once every 3 months.

The combination of reduced lesion growth and improved visual acuity suggests the therapy may influence both retinal structure and function, according to the investigators.

"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," said Dr. Ambati, director of the Center for Advanced Vision Science and DuPont Guerry III Professor of Ophthalmology at the University of Virginia. He added that the findings warrant confirmation in phase 3 studies.

The multicenter US phase 2 study enrolled 30 participants with bilateral GA across nine clinical sites, evaluating a total of 60 eyes. In each participant, the worse-seeing eye received a K8 implant while the fellow eye served as an untreated control. Three dose levels—0.3 mg, 0.7 mg, and 1.05 mg—were evaluated, with implants administered at baseline and again at Month 3. The primary endpoint was the mean rate of GA growth analyzed using the FDA-preferred linear mixed-effects slope model. Imaging assessments were performed by masked readers at an independent reading center.

The prespecified BCVA analysis focused on eyes with extrafoveal lesions, where investigators considered there to be greater potential for preserving vision. The visual-acuity analysis adjusted for lesion growth rate, lesion focality, and low-luminance deficit.

Inflammasome Therapeutics reported no safety signals of concern through 6 months of follow-up. The company said there were no drug-related serious adverse events or dose-limiting toxicities, and no cases of endophthalmitis, intraocular inflammation, neovascular age-related macular degeneration, retinal vasculitis, or optic neuropathy.

The investigational therapy is delivered using a preloaded 24-gauge intravitreal injector and is designed to provide sustained drug release over three months without requiring cold-chain storage.

The company said it plans to initiate a global phase 3 pivotal development program for K8 in patients with GA.