These days, when I see a patient with newly diagnosed active neovascular age-related macular degeneration (ARMD) on my clinic schedule, it is a no-brainer that I’m likely to recommend an intravitreous injection with an antivascular endothelial growth factor agent. Even though the prospect of a needle in the eye is still scary for many patients, it is always reassuring to explain that with long-term treatment they have a high probability of maintaining or even improving their vision. As the use of antivascular endothelial growth factor therapy has dramatically improved outcomes for neovascular age-related macular degeneration, our attention has turned to other forms of macular pathology.
I only wish I had something nearly as effective for patients with vision loss from non-neovascular ARMD. It is demoralizing to watch a patient irreversibly lose vision from creeping geographic atrophy (GA) while being unable to offer anything to help. And although the tempo of vision loss from GA is usually slower than that associated with choroidal neovascularization, functional loss from “dry” ARMD can substantially and negatively impact a patient’s quality of life. Thus, effective treatment to prevent GA progression is a still a critical unmet medical need for our patients with ARMD.
Four years ago, positive results from the phase 2 MAHALO trial suggested that lampalizumab, an antigen-binding fragment of an antibody to complement factor D, might slow the growth of atrophic macular lesions. The complement pathway has been strongly implicated in the pathogenesis of AMD, so scientific rationale was promising for efficacy of this drug in ARMD. Unfortunately, more recent data made available in September 2017 show that the primary end point was not met in the Spectri trial, 1 of 2 ongoing phase 3 studies of this agent for eyes with dry ARMD. In Spectri, lampalizumab did not reduce change in GA lesion area over 1 year as compared with sham treatment. Dosing has been suspended in this study until results from the companion trial, Chroma, have been evaluated. While it is theoretically possible that Chroma could provide positive results suggestive of benefit from lampalizumab treatment for GA, it seems unlikely that the 2 trials would differ so substantially in their estimation of treatment effect. The Chroma results will be available in November 2017, so there is not much longer to wait.
Although it is disappointing that we may not have a newly effective therapy for eyes with non-neovascular ARMD, even if lampalizumab does not prevent GA progression, there are still valuable lessons to be learned from both Spectri and Chroma. These studies provide an unparalleled large cohort in which to assess the natural history of eyes with GA. Through the rigorous phenotyping of this group of eyes, we have the opportunity to elucidate novel anatomic biomarkers of GA progression on spectral domain optical coherence tomography. Furthermore, we may be able to better understand how functional changes accompany growth of GA lesions through the quality-of-life questionnaires and visual function testing performed in these trials.
There is no lack of other potential agents being evaluated for prevention of GA onset or worsening. The clinicaltrials.gov website lists 36 active studies for GA, 23 of which are currently enrolling participants. Hopefully one or more of these novel therapies under investigation will demonstrate efficacy and successfully achieve registration status as an approved therapy for eyes with dry AMD. In the meantime, we should and will continue the search for new molecular pathways and physiologic targets of interest that might one day add to our armamentarium of tools in the fight to save vision for our patients with ARMD.