Not All is Dry with Dry AMD

And now…finally…some good news in dry AMD!

Geographic atrophy (GA) remains a significant unmet need that has been met with great attention by investigators and industry. However, until now, all prior trials of therapeutic interventions for GA have failed. Apellis Pharmaceuticals has changed that paradigm, finally giving us some hope for a treatment in this challenging disease.


According to a press release, Apellis tested APL-2 in a phase 2 trial for GA, and met the primary endpoint at 12 months. APL-2 binds to C3 and C3b and acts to functionally inhibit complement activation. The asset was injected intravitreally monthly, and was tested versus a sham control in a multicenter, randomized, single-masked trial design. Exposure to the experimental agent resulted in a statistically significantly reduction in the rate of GA lesion growth by 29% compared with sham (P = .008). In addition, when given in a q2 month dosing regimen, the rate of GA reduction was 20% (P = .067).

Interestingly, the drug was more effective in the second half of the trial, where during the second 6 months, the outcomes were superior to the data from the first 6 months. In the latter half of the trial, post hoc analyses demonstrated a 47% rate of GA reduction with monthly doing (< .001) and 33% with q2 month drug exposure.

The study was not without concerns. While the experimental molecule did reduce the rate of GA enlargement, treated eyes also demonstrated a higher incidence of conversion to neovascular AMD. While this is certainly an issue that needs to be carefully monitored in a larger study, the patients who developed this were treated with anti-VEGF therapy and did not lose vision as a result.

This sounds great, but we have been down this path before. There are a myriad of experimental assets that have looked promising in phase 2, but have failed when tested in a larger, powered investigation. Will APL-2 become a true game changer, or join the ranks of the defeated that have taken on GA before? Only time will tell, but the company should be praised for the excellent work and outcomes to date.

Jonathan Prenner, M.D.