REDWOOD CITY, Calif.—While the COVID-19 pandemic has slowed or halted many clinical trials, causing delays in enrollment or complicating patient treatments, some trials are still advancing. One such study is Adverum Biotechnologies Inc.’s OPTIC Phase 1 trial of ADVM-022, which recently reported new interim clinical data as well as an update on ongoing enrollment.
ADVM-022 is a gene therapy being developed as a treatment for wet age-related macular degeneration (AMD). It uses a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette.
The OPTIC Phase 1 trial is a multi-center, open-label, dose-ranging trial evaluating the safety and tolerability of a single intravitreal dose of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. Patients in Cohorts 1 and 4 will receive ADVM-022 at a dose of 6 x 10^11 vg/eye, though Cohort 4 will receive prophylactic steroid eye drops instead of the oral steroids in Cohort 1. Similarly, patients in Cohorts 2 and 3 receive ADVM-022 at a dose of 2 x 10^11 vg/eye, with patients in Cohort 3 receiving prophylactic eye drops and Cohort 1 receiving oral steroids. The primary endpoint is safety and tolerability after a single intravitreal injection, and enrollment is currently underway for Cohort 4.
The data presented were current as of the cutoff date of April 1. Adverum noted that ADVM-022 has demonstrated ongoing efficacy and durability, with no rescue injections needed in six of six patients in Cohort 1, and no rescue injections needed in eight of 11 patients in Cohort 2. The safety profile is favorable, with only mild-to-moderate adverse events and no evidence of vasculitis, retinitis or choroiditis. Inflammation has been observed, but it has responded to steroid eye drops, and a six-week course of eye drops has in fact led to fewer adverse events and less inflammation than a 13-day prophylactic regimen of oral steroids. Patients in Cohort 3 have presented with early anatomic and vision improvements, including a reduction in central retinal thickness and a mean best-corrected visual acuity gain of +6.8 letters.
“I am pleased to say that all of the OPTIC data continues to support what we have previously reported, including robust efficacy and evidence of a dose response from a single injection of ADVM-022; further evidence of long-term durability, with all Cohort 1 patients now out beyond one year and zero recuse injections; and lastly, and importantly, a favorable safety profile,” Leone Patterson, president and CEO of Adverum, remarked in a company webcast regarding the OPTIC results.
Dr. Arshad M. Khanani, director of clinical research at Sierra Eye Associates and a principal investigator in the OPTIC trial, said, “It’s impressive to see the long-term durability demonstrated at the higher dose of ADVM-022 in a patient population that previously required frequent injections to maintain their vision, and are now beyond one year of follow-up with no rescue injections. Additionally, preliminary evidence in Cohort 3 shows vision and anatomical improvements, and that the six-week prophylactic steroid eye drop regimen is effective at minimizing early ocular inflammation. These are very positive data, and it is exciting to see that this intravitreal gene therapy has the potential to completely change the treatment paradigm for patients with wet AMD.”
Intravitreal injections of anti-VEGF are the current standard-of-care treatment for wet AMD, but they come with a high treatment burden—injections are required every four to 12 weeks, and patient compliance can be difficult.
“We are encouraged by the robust efficacy signal and evidence of a dose response in the OPTIC trial with interim data from three cohorts. Also, momentum in OPTIC is strong, as we are currently enrolling patients in Cohort 4 at the higher dose of 6 x 10^11 vg/eye using the same steroid regimen as Cohort 3,” commented Aaron Osborne, chief medical officer of Adverum. “We look forward to reporting additional data in the second half of this year from OPTIC. Beyond wet AMD, we are on track with our plans to advance ADVM-022 in diabetic retinopathy, our second indication, and we continue to expect to begin enrolling patients in our planned clinical trial in the second half of this year.”