Benzinga | Nov 14, 2020 10:08AM EST

Adverum Biotechnologies Announced Positive Interim Data from Cohorts 1-4 from OPTIC Phase 1 Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMD

Adverum Biotechnologies, Inc. (NASDAQ:ADVM) today 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," said Laurent Fischer, M.D., chief executive officer of Adverum. "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 maintainedMean CRT2 maintained to improvedDurability 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/mLSubstantial reduction in annualized anti-VEGF injection frequency3 following ADVM-022in patients who previously required frequent injections:High dose: 99% reductionLow dose: 85% reductionMost patients are supplemental anti-VEGF injection free in OPTIC:High dose: 14/154patients injection freeLow dose: 10/155patients injection freeADVM-022 continues to be well tolerated with a favorable safety profile at both high and low dosesAll 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 timeNo clinical or fluorescein evidence of posterior inflammationNo vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitisOPTIC Phase 1 Clinical Trial Data:

Results Following a Single ADVM-022 Dose: Cohort 1Cohort 2Cohort 3 Cohort 4Patients n=6 n=6 n=9 n=9Median (Range) Follow-up Visit (Weeks) 86(64 to 92) 64(64 to 68) 48(32 to 48) 16(12 to 24)ADVM-022 DoseHigh dose6 x 10^11 vg/eye Low dose2 x 10^11 vg/eye Low dose2 x 10^11 vg/eye High dose6 x 10^11 vg/eyeProphylactic Steroid Regimen13-day oral 13-day oral 6-week eye drops 6-week eye dropsSupplemental Anti-VEGF Injection Use: Number of patients supplemental injection free 6/6 patients 3/6 patients 7/9 patients 8/9 patientsTotal supplemental anti-VEGF injections 0 injections 17 injections in 3 patients 8 injections in 2 patients 1 injection in 1 patientFollow-up BCVA1 and CRT2: All Patients All Patients Supp. IVT-free Patients 50% (3/6) All Patients

Supp. IVT-free Patients 78% (7/9) N/ABCVA mean change from baseline (letters) -2.5 +0.2 +1.0 -0.9 +4.1 N/ACRT mean change from baseline (m) -19.7 m -1.0 m -23.7 m -113.4 m -132.7 m N/AOcular Inflammation and Management: % patients with any cellular inflammation at most recent visit 33% 0% 11% 22%Average # of daily steroid eye drops6 1.2 0.5 0.8 1.91 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) = (numberof 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, M.D., F.A.C.S, 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 PlansADVM-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 2021Initiate a pivotal trial mid-2021ADVM-022 in DME

Present clinical data from INFINITY Phase 2 trial in the second half of 2021Adverum Webcast:Date: November 14, 2020Time: 7:30 9:00 am PT (10:30 am 12:00 pm ET)Presenters:

Carl D. Regillo, M.D., F.A.C.S, director of the Wills Eye Hospital Retina Service and investigator in the OPTIC Phase 1 trialSteven Yeh, M.D., associate professor, director, section of uveitis and ocular immunology, Emory Eye CenterDavid S. Boyer, M.D., senior partner, Retina-Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology, University of Southern California/ Keck School of Medicine, Los Angeles, investigator in the OPTIC Phase 1 trial