Adverum Biotechnologies Announces Positive Interim Data From OPTIC Phase 1 Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMD

Adverum Biotechnologies announced positive new interim data from Cohorts 1-4 of the OPTIC phase 1 clinical trial of ADVM-022 intravitreal (IVT) injection gene therapy in patients requiring frequent anti-VEGF injections for their wet age-related macular degeneration (AMD).

“With these impressive OPTIC data and the removal of the partial clinical hold on ADVM-022 by the FDA, our goal is to continue to advance into pivotal trials to demonstrate the transformative potential of our gene therapy,” Laurent Fischer, MD, chief executive officer of Adverum, said in a company news release. “We are excited that ADVM-022 has the potential to be a “one and done” IVT injection that may dramatically reduce the treatment burden for the millions of patients with wet AMD and DME worldwide. Particularly during COVID-19, we are reminded of the benefits that ADVM-022, a novel gene therapy that has demonstrated long-term treatment benefit after one in-office IVT injection, could deliver to patients. Our Adverum team is laser-focused on accelerating the development and future commercial launch plans for ADVM-022. I am humbled by the dedication of the retina specialists and their staff, and our employees, to help progress our clinical trials which generate the data necessary to drive our mission of helping patients with severe ocular diseases.”

Adverum reported new interim data from the OPTIC trial (October 15, 2020 cutoff date) that further demonstrate the transformative potential of ADVM-022 to greatly reduce the anti-VEGF injection burden for patients with wet AMD:

• ADVM-022 continues to maintain efficacy at both high and low doses (n=30)
  • Mean BCVA¹ maintained
  • Mean CRT² maintained to improved
• Durability out to 92 weeks from a single IVT injection with zero supplemental injections in Cohort 1 (high dose)
• Robust preliminary aqueous anti-VEGF protein expression observed at 18 months in Cohort 1 (high dose)
  • Mean aqueous anti-VEGF protein level 1840 ng/mL
• Substantial reduction in annualized anti-VEGF injection frequency³ following ADVM-022 in patients who previously required frequent injections:
  • High dose: 99% reduction
  • Low dose: 85% reduction
• Most patients are supplemental anti-VEGF injection free in OPTIC:
  • High dose: 14/15⁴ patients injection free
  • Low dose: 10/15⁵ patients injection free
• ADVM-022 continues to be well tolerated with a favorable safety profile at both high and low doses
  • All ADVM-022-related ocular adverse events (AE) were mild (78%) to moderate (22%)
  • Ocular inflammation, when observed, has been responsive to steroid eye drops and overall is decreasing over time
  • No clinical or fluorescein evidence of posterior inflammation
    • No vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis

OPTIC Phase 1 Clinical Trial Data:

1 Best corrected visual acuity (BCVA)
2 Central retinal thickness (CRT)
3 Annualized rate (Before) = (number of IVTs in 12 months prior to ADVM-022) / (days from the first IVT in the past 12 months to ADVM-022 / 365.25)
Annualized rate (After) = (number of aflibercept IVTs since ADVM-022) / (days from ADVM-022 to the last study follow-up / 365.25)
4 All patients from Cohort 1 (n=6) and Cohort 4 (n=9)
5 All patients from Cohort 2 (n=6) and Cohort 3 (n=9)
6 Average calculated across entire cohort at their last follow up visit

Carl D. Regillo, MD, FACS, director of the Wills Eye Hospital Retina Service said, “The sustained anatomical response observed in OPTIC in my experience is unprecedented, extending out beyond 18 months following a single intravitreal injection of ADVM-022. In addition, ADVM-022 has been well tolerated, and ocular inflammation, when observed, is responsive to steroid eye drops and decreases over time. ADVM-022 is a novel gene therapy that has demonstrated the potential to transform the treatment of patients living with wet AMD.”

Aaron Osborne, MBBS, chief medical officer of Adverum, added, “In OPTIC, we have enrolled the wet AMD patients requiring frequent injections to manage their condition, so we are very pleased with the significant reduction in anti-VEGF treatment burden demonstrated in both the high and low dose of ADVM-022. Additionally, the robust ocular anti-VEGF levels are a clear indication of ADVM-022’s stable, continuous therapeutic protein expression out to 18 months. We will continue to monitor our 30 patients and plan to present longer-term data, including additional anti-VEGF protein expression data from patients who consent to aqueous taps, in the first half of 2021. We are planning for our end-of-Phase 1 meeting with the U.S. FDA on our development program, including the initiation of our first pivotal clinical trial in wet AMD in mid-2021. With these continued impressive data, we believe that both doses warrant further investigation.”

Future Plans
ADVM-022 in wet AMD

• Present longer-term data from OPTIC phase 1 trial, including additional anti-VEGF protein expression data, in the first half of 2021
• Initiate a pivotal trial mid-2021

ADVM-022 in DME

• Present clinical data from INFINITY phase 2 trial in the second half of 2021