Adverum Biotechnologies announced new interim clinical data from the OPTIC phase 1 dose-ranging clinical trial of ADVM-022 intravitreal injection gene therapy. OPTIC includes treatment-experienced patients with wet age-related macular degeneration (AMD).
The data were being presented by David S. Boyer, M.D., senior partner, Retina-Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology with the University of Southern California/Keck School of Medicine in Los Angeles, at the Angiogenesis, Exudation, and Degeneration 2020 Annual Meeting in Miami.
A copy of the presentation is available on the Adverum corporate website under Events and Presentations in the Investors section.
For the first time, data are being presented from patients in cohort 2 (n=6) at 24 weeks following treatment with a single intravitreal injection of a three-fold lower dose of ADVM-022 (2 x 10^11 vg/eye) compared to the cohort 1 dose (6 x 10^11 vg/eye). New data as detailed in the table below include:
- ADVM-022 demonstrated a robust efficacy signal and evidence of a dose response:
- Cohort 1: 6 of 6 patients remain rescue-injection-free at a median follow up of 50 weeks, with 3 patients at 52 weeks.
- Cohort 2: 4 of 6 patients remain rescue-injection-free at 24 weeks at the lower dose.
- In both cohorts combined, 10 of 12 (83%) patients remain rescue-injection-free. For these patients:
- Vision was generally maintained as demonstrated by stable mean best corrected visual acuity (BCVA) compared to baseline.
- Retinal anatomy improvements were achieved and maintained as demonstrated by mean central subfield thickness (CST) compared to baseline.
- ADVM-022 continues to demonstrate a favorable safety profile and be well tolerated with no drug-related or procedure-related serious adverse events (SAEs), no drug-related systemic adverse events, and no adverse events meeting the criteria for dose-limiting toxicities (DLTs).
- ADVM-022-related adverse events (AEs) have been mild (71%) to moderate (29%).
- Low-grade ocular inflammation was commonly reported and was responsive to steroid eye drops.
OPTIC Phase 1 Clinical Trial Data:
|Results Following a Single ADVM-022 Dose:||Cohort 1
|Dose ADVM-022||Higher Dose
6 x 10^11 vg/eye
2 x 10^11 vg/eye
|Follow-up (median)||50 weeks||24 weeks|
|Number of patients requiring anti-VEGF rescue injections||0/6 patients||2/6 patients|
|Total anti-VEGF rescue injections||0 injections||6 injections|
|Systemic adverse events||0||0|
|Dose-limiting toxicities (DLTs)||0||0|
|Serious adverse events (SAEs)1||1||0|
|Drug/procedure related SAEs||0||0|
|Follow-up||44 weeks (median)||24 weeks|
|Change in BCVA2:||Full cohort||Rescue-free patients|
|Mean (ETDRS letters)3||-1.0||-4.8||-0.8|
|Range (ETDRS letters)||-7 / +7||-19 / +16||-14 / +16|
|Change in CRT3:|
|Range (mm)4||-117 / +32||-61 / -8||-61 / -8|
|1||This event (retinal detachment) was deemed unrelated to ADVM-022 or any study procedure.|
|2||Best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) (i.e., sight charts). Data through December 1, 2019 (Cohort 1).|
|3||Central retinal thickness (CRT), also referred to as central subfield thickness (CST) assessed using Optical Coherence Tomography (OCT) imaging and measured by an independent Central Reading Center Data through December 1, 2019 (Cohort 1).|
|4||BCVA and CST values for patient with retinal detachment (unrelated to study treatment) used last observations prior to detachment.|
“I am very encouraged that this difficult-to-treat patient population enrolled in OPTIC is maintaining vision and anatomical improvements for an extended period of time,” David S. Boyer, MD, senior partner, Retina-Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology with the University of Southern California/Keck School of Medicine in Los Angeles, California, said in a company news release. “Additionally, ADVM-022 continues to be safe and well tolerated, with ocular inflammation that is manageable with steroid eye drops. Patients with wet AMD and their caregivers carry a significant treatment burden from the current standard-of-care anti-VEGF injections, and real-world vision outcomes are suboptimal due to undertreatment. ADVM-022 as a one-time intravitreal injection therapy could transform the treatment paradigm for patients and their caregivers.”
Aaron Osborne, MBBS, chief medical officer of Adverum, added, “ADVM-022 has demonstrated a robust efficacy signal and evidence of a dose response in the OPTIC phase 1 trial with data from 12 patients and two doses now available. Patients in cohort 2 received a three-fold lower dose of ADVM-022 than in cohort 1, and 4 of 6 of these patients are rescue injection-free through 24 weeks, whilst all 6 patients in cohort 1 remain rescue free with a median follow up of 50 weeks. OPTIC is progressing well, with the key objectives for cohorts 3 and 4 being to further evaluate dose response and to assess a 6-week prophylactic course of steroid eye drops instead of the 13-day oral steroid prophylaxis used in cohorts 1 and 2. We look forward to presenting clinical data from all four cohorts of OPTIC during this important year in the clinic for our novel gene therapy, ADVM-022.”