MENLO PARK, Calif.—As 2019 wound to a close, Adverum Biotechnologies Inc. shared data from the first cohort of its Phase 1 OPTIC trial of ADVM-022 in wet age-related macular degeneration (AMD), showing that a single administration can help maintain vision for up to eight months. Adverum presented the data at the Retina Subspecialty Day Program of the American Academy of Ophthalmology (AAO) 2019 Annual Meeting.
ADVM-022 consists of a propriety vector capsid, AAV.7m8, which carries an aflibercept coding sequence under the control of a proprietary expression cassette. The therapy is meant to offer long-term efficacy, reduce frequent anti-VEGF injections, improve patient compliance, and to improve vision outcomes for patients with wet AMD and diabetic retinopathy.
Wet AMD is an aggressive form of age-related macular degeneration in which abnormal blood vessels grow underneath and into the retina, and then leak fluid and blood into and beneath the retina, leading to vision loss. At present, the standard of care for treating wet AMD is anti-VEGF intravitreal injections every four to eight weeks, and compliance with such a frequent regimen is burdensome for patients. An estimated 3 million individuals suffer from wet AMD globally.
“There’s a tremendous unmet need. I do remember during my training when Lucentis was approved, and it was revolutionary because patients no longer went blind,” remarked Dr. Szilárd Kiss, retinal specialist and presenter of the OPTIC data at AAO, in a webcast of a key opinion leader discussion of the first cohort data. “But it came at a cost, and that cost is frequent injections. So now when a patient comes in to me, they either know somebody who’s had injections or they’ve heard of injections, so the concept of a needle in the eye is not the biggest hurdle. The concept is ‘Doc, how many and for how long?’”
Dr. Dante Pieramici, co-director of the California Retina Research Foundation, managing partner of The California Retina Consultants and investigator in the OPTIC trial, said, “An intravitreal gene therapy that can significantly reduce the number of injections required to maintain vision would be welcomed by patients with wet AMD as well as their caregivers and physicians. I’m encouraged by the recently presented clinical data from the first cohort of the OPTIC trial showing that the therapy was safe and well tolerated with no rescue injections required in patients who previously required frequent anti-VEGF injections to control their wet AMD.”
The OPTIC Phase 1 trial is a multi-center, open-label trial evaluating the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. The primary endpoint of the trial is the safety and tolerability of this treatment regimen, with secondary endpoints including change in best-corrected visual acuity, change in central subfield thickness and macular volume, mean number of anti-VEGF rescue injections and percentage of patients needing anti-VEGF rescue injection. Each patient will be followed for two years.
The first and second cohorts consist of six patients each, with the third and fourth cohorts consisting of nine patients each. Adverum dosed the first patient in the third cohort in late October.
For this recently announced data, the median follow-up for patients in the first cohort was 34 weeks, with a range of 28 to 44 weeks. A single ADVM-022 injection proved sufficient to maintain vision in the treatment-experienced patients, with zero rescue injections required based on protocol-defined criteria. Additionally, retinal anatomy improvements seen on OCT scans were sustained, and vision acuity was maintained, with a stable best corrected visual acuity (BCVA) compared to baseline. The treatment was found to be safe and well tolerated, with no serious adverse events, no dose-limiting toxicities and no Grade 3 adverse events. As noted by Kiss in the webcast, inflammation was manageable with steroidal eye drops.
“The clinical profile of ADVM-022 demonstrates this gene therapy’s potential to be a significant advance for patients with wet AMD. It is very encouraging that there continues to be zero rescue injections in this cohort of treatment-experienced patients with more than six months follow-up on all patients … We look forward to being able to deliver this novel intravitreal gene therapy candidate as soon as possible to patients with wet AMD and diabetic retinopathy, our second indication for ADVM-022. We are grateful for all of the investigators, patients and caregivers who continue to participate in the OPTIC trial,” said Aaron Osborne, chief medical officer of Adverum.
In terms of upcoming milestones for the OPTIC trial, enrollment for the fourth cohort is slated to begin in Q1 2020, with 52-week data from the first cohort and 24-week data from the second cohort to be presented in the first half of 2020. Adverum also intends to submit an Investigational New Drug application for ADVM-022 for the treatment of diabetic retinopathy in H1 2020.