Adverum Biotechnologies disclosed in late April that a patient treated with experimental gene therapy for diabetic macular edema (DME) experienced an unexpected drop in intraocular pressure, inflammation, and decreased vision. The patient has been treated and is getting better, but monitoring of the remaining patients revealed that four other patients have similar problems-two of them require surgery.
CEO Laurent Fischer said that Adverum, based in Redwood, California, does not yet know the cause of eye problems, and DME patients may have a variety of underlying diseases that may affect the eyes.But based on the toxicity that appears to be associated with high-dose gene therapy, Adverum will No longer develop Gene therapy for the treatment of DME.
“Gene therapy drug development is a relatively new field,” Fisher said on a July 22 conference call. “We are pushing boundaries, and as we all know, finding a dose in many projects has always been a challenge.”
The second phase of the study aimed to evaluate two doses of Adverum gene therapy ADVM-022. Eye problems reported in April were observed in the 30th week of the clinical trialAfter learning of the problem, the company lifted the veil of research and began investigating to find out the cause.
Chief Medical Officer Julie Clark said that after treatment, some of the intraocular pressure and vision can be restored in the treated eyes. She added that it is too early to speculate on the patient’s recovery. But the other four patients whose intraocular pressure dropped rapidly did not respond to steroids and needed additional treatment. These problems occurred between 16 and 36 weeks after receiving the high dose. No similar problems have been reported among people receiving lost doses of gene therapy.
Although Adverum no longer plans to develop ADVM-022 for DME, the research continues to follow patients and review incoming data. Clark said that all patients in the study are expected to pass the 36th week of the study by the end of September. In order to reduce the risk, the company now recommends the use of systemic immunomodulatory drugs for gene therapy. Adverum plans to present more data at the annual meeting of the American Association of Retinal Experts, which is scheduled to be held from October 8th to 12th.
DME is the fluid that accumulates in the macula of the retina, which can cause vision problems and even blindness. This condition can be treated with the FDA-approved Regeneron Pharmaceuticals drug Aflibercept (Eylea). The drug, which is injected once a month, is a fusion protein that can block VEGF, a signaling protein that promotes the growth of new blood vessels. Adverum gene therapy uses adeno-associated virus vectors to deliver the coding sequence of aflibercept to eye cells. This is a one-time treatment designed to enable the eye to maintain the production of therapeutic proteins.
In addition to DME, Adverum is also testing ADVM-022 in a separate study for wet age-related macular degeneration, which is caused by blood vessels leaking fluid or blood into the macula. This liquid can blur vision or cause blind spots. Aflibercept injection is also approved for the treatment of wet AMD.
The intraocular pressure and inflammation observed in the DME study were not reported in the phase 1 test of gene therapy for wet AMD, either in low or high doses. Adverum said that long-term data from 30 patients in the wet AMD study show that the therapy has long-term durability and the efficacy is maintained.According to the result came up with At the Vision and Ophthalmology Research Association in April, 60% of patients had no injections for more than a year, and after a single low-dose injection, the patient’s annual injection frequency was reduced by 85%. The company plans to evaluate low-dose ADVM-022 in a future phase 2 study of wet AMD.
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