ADVM-022 was also granted PRIME designation by the EMA on June 24, 2022.
ADVM-022, an investigational adeno-associated virus (AAV) vector gene therapy by Adverum Biotechnologies, improved anatomic outcomes in patients with wet age-related macular degeneration (AMD) treated in the phase 1 OPTIC trial (NCT03748784).1
Data from the OPTIC trial were presented at the 2022 Macula Society Annual Meeting, June 8-11, in Berlin, Germany. Investigators also presented evidence of consistent and continuous aflibercept protein expression at therapeutic levels.
“We are thrilled to highlight new data indicating that therapeutic levels of aflibercept expression, following a single administration of ADVM-022, are sustained out to 3-years, demonstrating its potential for continuous long-term clinical benefit. Additionally, we are pleased to present compelling data relating to patients’ baseline levels of neutralizing antibodies and treatment efficacy.,” Richard Beckman, MD, chief medical officer, Adverum Biotechnologies, said in a statement.1
Over 80% of patients screened in the OPTIC study had baseline NAbs titers of <1:125 against AAV.7m8, the proprietary AAV vector used. In these patients, the 2E11 dose yielded sustained therapeutic aflibercept levels comparable to the 6E11 dose. The mean annualized rate of anti-vascular endothelial growth factor (VEGF) injections was reduced by 81% in all participants treated at this dose and 93% in participants with low NAbs titers. The annual rate of central subfield thickness (CST) fluctuation also was reduced by 70% (± 50 µm) in participants treated at this dose level with low NAbs titers.
“Fluctuations in macular fluid as measured by CST are associated with the current treatment paradigm of frequent repeated bolus anti-VEGF injections. Recent literature has demonstrated that greater fluctuations are associated with poor long-term visual outcomes. These data suggest that by delivering continuous levels of aflibercept, ADVM-022 can dramatically reduce fluctuations in CST which may translate into better long-term vision,” Beckman added.1
The 3-year data presented also demonstrated that ADVM-022 was well tolerated, with no participants in the 2E11 dose group experiencing inflammation that required topical corticosteroids at the most recent follow up. There has been no evidence of correlation between baseline NAbs and inflammation or other adverse events.
“As a practicing physician with a deep understanding of the wet AMD patient population’s needs, the longer duration of efficacy from weeks to years, as well as the favorable safety profile of ADVM-022 warrants further development of the 2E11 dose, and given the NHP data showing similar aflibercept expression at 6E10 vg/eye, I am eager to see the efficacy and safety profile of the new, lower 6E10 dose in the upcoming phase 2 trial,” Szilárd Kiss, MD, Bob and Dolores Hope – Robert M. Ellsworth, M.D. Distinguished Associate Professor in Ophthalmology, Weill Cornell Medical College, added to the statement.1
Adverum is planning to initiate a phase 2 study investigating the 2E11 dose as well as a lower 6E10 vg/eye dose along with a modified prophylactic steroid regimen that includes local and systemic steroids. The company plans to dose the first patient in the third quarter of 2022.2 ADVM-022 was also granted Priority Medicines (PRIME) designation by the EMA for the treatment of wet AMD on June 24, 2022.
“Following the encouraging results seen in the OPTIC trial in wet AMD, our PRIME designation recognizes the broad potential of ADVM-022..." Laurent Fischer, MD, president and chief executive officer, Adverum, said in a separate statement.2 “The current standard of care in wet AMD, a highly prevalent disease, requires frequent anti-VEGF injections in the eye and is a lifelong burden for many patients and their caregivers. We believe ADVM-022 has the potential to provide a durable, safe and cost-effective in-office treatment option that addresses the needs of these patients, and their families, as well as retina specialists and health systems worldwide.”