Following a significant adverse event in which a patient lost vision in an eye treated with ADVM-022, Adverum Biotechnologies has unveiled the details of its Phase 2 trial of this gene therapy for diabetic macular edema.
An overgrowth of blood vessels
Wet age-related macular degeneration (AMD) is caused when blood vessels from underneath the retina begin to grow into it. When these vessels leak fluid into the retina, it results in macular edema. This problem is also frequently associated with diabetes, as it causes damage to the small blood vessels within the retina; this problem is known as diabetic macular edema (DME).
The immediate cause of wet AMD is vascular endothelial growth factor (VEGF), which encourages the development of abnormal blood vessels within the retina. Therefore, it is no surprise that the current standard of care for wet AMD is a regular injection of anti-VEGF drugs, such as afilbercept, which binds to VEGF more tightly than natural receptors .
A gene therapy to replace regular injections
The purpose of ADVM-022 is to cause cells in the eye to express afilbercept themselves, obviating the need for injections of anti-VEGF drugs directly into the eyeball every four to twelve weeks. Ideally, this would solve problems with patient compliance and regular administration of expensive drugs, and it would require considerably fewer visits to the doctor’s office.
In a previous Phase 1 trial, ADVM-022 caused only mild and moderate side effects at both low and high doses. At the lower dose, inflammation was mild and responded well to steroid eyedrops.
This new Phase 2 trial has enrolled 36 patients, comparing low-dose and high-dose ADVM-022 against direct injections of afilbercept. In this study, an unexpected adverse event occurred; one patient lost fluid and vision in the treated eye while experiencing extreme inflammation. It is not yet known what role ADVM-022 played in this event.
Wet AMD is a serious, progressive age-related disease that afflicts millions of people, and while forcing the expression of a specific protein to stop blood vessel growth is a less-than-ideal solution for people who wish to see its root causes dealt with, the idea that we can use gene therapies to cure age-related diseases is certainly appealing. We hope that the adverse event reported in the Phase 2 trial was very rare or unrelated and that such a gene therapy is suitable for replacing simple afilbercept, or other anti-VEGF, injections as the standard of care.
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 Browning, D. J., Kaiser, P. K., Rosenfeld, P. J., & Stewart, M. W. (2012). Aflibercept for age-related macular degeneration: a game-changer or quiet addition?. American journal of ophthalmology, 154(2), 222-226.