Results of the phase 1 OPTIC trial reveal ADVM-022 was effective at maintaining visual acuity in patients with wet AMD with a favorable safety profile.
Results of a phase 1 trial presented at the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco, suggest a gene therapy treatment for wet age-related macular degeneration(AMD) could be on the horizon within 3 to 5 years.
Presented by Szilard Kiss, MD, results of the phase 1 OPTIC trial revealed the intravtireal gene therapy ADVM-022 had the ability to maintain vision with a one-time injection and was well-tolerated, with no serious adverse events (SAEs), no dose limiting toxicities (DLTs), and no Grade 3 adverse events.
OPTIC, which is a 2-year, multicenter, prospective clinical trial, examined the use of ADVM-022 in a group of 6 patients who had previously required frequent anti-VEGF injections to maintain vision. Mean age of the study cohort 79 years, mean time since diagnosis was 3.3 years, and mean number of injections in 8 months prior to screening was 6.2. Additionally, investigators noted the range of prior anti-VEGF injections was from 7 to 109.
While information on the prespecified 24-week results have been previously presented, the presentation at AAO 2019 featured additional data with median follow-up of 34 weeks—investigators pointed out that follow-up ranged from 28 to 44 weeks.
In terms of safety, zero rescue injections were required for any patient based upon-protocol defined criteria. Criteria included the loss of 10 or more letters in BCVA from baseline and intraretinal or subretinal fluid observed through SD-OCT, an increase in central subfield thickness greater than 75 µm from baseline, or the presence of vision-threatening hemorrhage due to macular degeneration.
Additional data presented included retinal anatomy improvements observed on OCT scans were sustained, BCVA remained stable compared to baseline, and ADVM-022 was not associated with any SAEs, DLTs, and no Grade 3 AEs. Investigators noted the mean change in BCVA was -1.5—the minimum change was -9 and maximum change was +5.
Kiss, director of clinical research and associate professor at Weill Cornell Medical College, sat down with MD Magazine® at AAO 2019 to discuss the potential for ADVM-022.
MD Mag: What is ADVM-022 and what do trial results indicate about its efficacy as treatment for wet AMD?
Kiss: Patients with age-related macular degeneration require frequent injections in order to maintain their vision. The injections of anti-VEGF therapy work very well, but patients have to come in 8, 9, 10 times per year indefinitely. So the unmet need is really to transform those 8 to 10 visits into perhaps a one and you're done. It would be nice if that one and you're done was done in the office and that's where ADVM-022 comes in.
ADVM-022 is a gene therapy that delivers aflibercept. Aflibercept is a medication that we use routinely in our patients with macular degeneration. With ADVM-022, we inject the medication into the eye and the gene therapy allows the eye itself to make the aflibercept protein. With the aflibercept protein being made in the eye, there is really no need for intravitreal injections.
In the OPTIC trial, which is a phase 1, 2-year, multicenter, prospective clinical trial, we injected ADVM-022in patients who required injections for wet AMD. In those patients, on average they needed about 35 injections prior to enrolling in OPTIC. These patients were also not treatment-naive—on average, about 3 and half years of diagnosis of wet AMD before they enrolled. In the first 6 subjects that were enrolled in cohort 1, we reported the 24 week data. With robust anatomical response and maintaining visual acuity patients did not require any rescue injections.
Here, we report even newer data. The follow-up out to October 1. The follow-up to October 1st was on average, about 8 months. One of the patients in the study was followed for over 10 months. The anatomical responses that we saw in the 6-month data continued out to the last follow-up. Patients did not require any injections and they maintained their vision, they also maintained the improvements on OCT.
So, when you think about how gene therapy, specifically gene therapy of ADVM-022, can transform this landscape—it can take patients who require frequent injections and turn it into a one-and-done therapy. One of the patients in the trial, more interestingly, required 109 injections prior to enrollment. Since receiving the gene therapies, this particular patients has not required any rescue injections with nearly 9 months of follow-up.
Now, these are 6 patients in the first cohort of the OPTIC trial. More definitely needs to be done, but with a safety profile that we are seeing, which is favorable, and with the efficacy profile that we're seeing, I think within the next 3 to 5 years we can expect gene therapy with anti-VEGF in the office treating our patients who now require frequent injections.