Adverum Biotechnologies’ eye disease gene therapy has traversed a rocky road of safety troubles, but the company — presenting new Phase 2 data in wet AMD — now believes it has a clear shot to a pivotal study early next year.
Its candidate, previously known as ADVM-022 and now called ixo-vec, is intended to reduce the frequency at which patients need to receive follow-up injections of Eylea after getting the gene therapy. Among 29 patients who received the dose Adverum intends to take into Phase 3, 76% were injection-free after 26 weeks.
Researchers presented the data at the American Society of Retina Specialists’ annual meeting in Stockholm. Another 29 patients received a higher dose, and 83% of these individuals remained injection-free after the same time period.
But Adverum is going with the lower dose because it can deliver similar efficacy to the high dose while provoking less inflammation, CEO Laurent Fischer told Endpoints News.
“We did a lot of work in the last several years to demonstrate in non-human primates that we could continue to lower the dose,” Fischer said. “We’ve achieved the goal of showing that we can lower the dose by three-to-10 fold from what we tested in the past, and that dose gives a similar level of efficacy.”
Adverum shares $ADVM were down about 4% premarket Wednesday and sank more than 16% in the hours after the opening bell.
Ixo-vec is designed to be injected directly into the eye, containing a gene that can prompt patients’ eyes to generate aflibercept (Eylea’s scientific name) on their own. The idea is that a one-time treatment will stop patients from having to receive continuous eye injections, as most find the process burdensome and uncomfortable.
It’s a similar concept to a program being developed by 4D Molecular Therapeutics, which also presented new data in Stockholm on Wednesday. Fischer said ixo-vec can separate itself from 4DMT’s program, called 4D-150, because ixo-vec can more reliably induce the cells to express aflibercept.
“We have more patients for longer that have been treated with ixo-vec with, I think, higher efficacy and a higher percentage of patients free of injection [than 4DMT’s drug],” Fischer said.
Adverum intends to present additional data later this year with longer follow-up, finalize the Phase 3 design in the fourth quarter and then launch the pivotal wet AMD trial in the first half of 2025. Right now, Fischer said he expects the study’s primary endpoint to measure visual acuity after 12 months in a non-inferiority setting compared to Eylea.
Ixo-vec is roughly five years removed from a safety scare that saw wet AMD patients taking a much higher dose suffer vision loss despite signs that the treatment improved retinal anatomy. The problems were followed by additional safety concerns that popped up in a diabetic macular edema trial in 2021, where five of 12 patients lost significant vision.
Three of those DME patients required surgery and all 12 were recommended to start “aggressive immunomodulatory treatments” to prevent further injury. The issues and subsequent stock collapse prompted Adverum to lay off 38% of its staff in early 2022. At the time, Adverum also scrapped its DME plans and moved forward only in a low dose for wet AMD.
Editor’s note: This story has been updated to include Adverum’s premarket stock movement, and again after the market opened.