Raj Maturi: Sirolimus in Conjunction With Aflibercept

Raj Maturi, MD: As you know, ant-VEGF agents are the best treatments for macular degeneration at new onset. Well, about 30 or 40% of these patients continue to have fluid in the retina, and fluid in the retina is often associated with vision loss, especially something in the layer called intraretinal fluid. Not subretinal fluid and not fluid elsewhere, but intraretinal fluid. I wanted to see if, in my patients, there were other things we could do besides anti-VEGF agents to try and improve that. So we looked at this other agent called sirolimus.

I wanted to see if the mTOR function, as well as the anti-inflammatory and anti-VEGF function, that it already had, would be beneficial in patients who had chronic macular degeneration that was not responsive. So we took about 20 subjects, and half of them we were treated with standard of care aflibercept (Eylea) every 8 weeks over the 36-week trial, and in the other half, we also gave them sirolimus. We gave sirolimus at baseline, week 4, and then every 8 weeks.

About half the patients in the sirolimus combination group with anti-VEGF did not need anti-VEGF agents at the last visit. So the edema reduced markedly in this group and almost went to 0 compared to the other group where they continued to have edema, although it improved there as well. Visual acuity was similar in both groups, although numerically the combination group did a little bit better.

The drug, obviously, is not FDA approved for this indication but may be by the end of the year for uveitis. If that's the case, this may be a place to look at sirolimus, as well as a few other drugs that are in the pipeline, for treatment for chronic AMD. We all have boatloads of patients who just are at maximum AMD therapy, at full label, full time point, and they just don't get better. It might be a place to try.