New drug class shows promise for geographic atrophy

A dose-ranging, phase 2 trial is fully enrolled to study an intraocular implant with sustained-release kamuvudines for patients with bilateral geographic atrophy. Inflammasome Therapeutics has developed this new class of therapeutics, and the first of these, K8, is being tested in patients with geographic atrophy, an advanced form of age-related macular degeneration.

Geographic atrophy is characterized by the development of lesions on the macula, which is the part of the retina responsible for detailed central vision. It affects about 1.5 million people in the United States and can lead to permanent vision loss.

K8 inhibits inflammasomes, which are part of the immune system and are activated in response to infectious microbes and molecules. Inflammasomes are linked to a variety of autoinflammatory and autoimmune diseases. In geographic atrophy, retinal pigment epithelium (RPE) triggers inflammasomes.

Kamuvudines are derivatives of a class of anti-HIV drugs, nucleoside reverse transcriptase inhibitors or NRTIs, which treat HIV by blocking the process that the virus uses to replicate. The NRTIs also have anti-inflammatory activity but they can result in mitochondrial toxicity. Kamuvudines, which were developed by Inflammasome Therapeutics’ cofounder Jayakrishna Ambati, M.D., retain the anti-inflammasome activity of NRTIs but are designed to be safer and with less toxicity.

In geographic atrophy, multiple toxic substances, including various forms of complement, amyloid beta, and oxidative stressors, trigger inflammasome activation that causes cells in the macula to slowly atrophy, Ambati explained in a news release. Over time, the area of atrophy grows in size and can lead to vision loss.

Inflammasome Therapeutics’ researchers have developed tiny, bioerodible, injectable implants that are injected into the vitreous, where they provide sustained release of K8 directly to the back of the eye. Injections are given every three months and are designed to block multiple disease pathways.

In the phase 2 trial, 30 patients have been recruited at nine centers throughout the United States. Patients with bilateral geographic atrophy receive low-, medium-, or high-dose implants at baseline and three months in one eye, and untreated eyes serve as controls. After three months, patients receive a second injection and are followed for another month. The primary endpoints of the trial are safety and efficacy assessed by changes in geographic atrophy lesion size growth, which is graded by an independent, masked reading center.

In September 2025, the company reported results from the first cohort of patients. Ten eyes had received the low-dose K8. The therapy reduced lesion area growth by 53% following three months of treatment. Vision trends were also positive. Eyes receiving the K8 implant had essentially stable vision with best corrected visual acuity that had increased an average of 1.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letters in K8-treated eyes. Untreated eyes continued to deteriorate, losing an average of 1.9 ETDRS letters. Early Treatment Diabetic Retinopathy Study is a standardized chart used to measure visual acuity.

Company officials expect pivotal trials of K8 to begin in 2026.

A second kamuvudine therapy, K9, is in development to treat thyroid eye disease and diabetic macular edema. K9 is an oral small molecule currently in phase 1 clinical trials.