Wet AMD Gene Therapy Demonstrates Promising Safety and Efficacy in Phase 1 Trial


Among the trial’s high dose cohort, 80% of patients did not require supplemental injections for over 2 years.

Adverum Biotechnologies’ investigational gene therapy ixoberogene soroparvovec (Ixo-vec; ADVM-022) demonstrated promising safety and efficacy in people with wet age-related macular degeneration (AMD) in long-term follow-up data from the phase 1 OPTIC clinical trial (NCT03748784), recently announced at the Retina Society Annual Meeting held November 2-5 in Pasadena, California.1

Among the participants in the trial, there was an 81% to 98% decrease in annualized anti-VEGF injections, and for patients in the extension study (OPTIC-EXT; NCT04645212), aflibercept protein was shown to continuously remain at therapeutic levels through 3 years. Among the trial’s high dose (6x1011) cohort, 80% of participants did not require supplemental injections for over 2 years, and among the trial’s low dose (2x1011) cohort, 53% of participants did not require supplemental injections for over 2 years. Additionally, through at least 2 years and among both dose cohorts, best-corrected visual acuity (BCVA) and central subfield thickness (CST) were either maintained or improved. 

In terms of safety, ixo-vec was generally well-tolerated, and inflammation in the higher dose cohort was responsive to topical steroids. All patients in the lower dose cohort were free of inflammation. A phase 2 clinical trial (LUNA; NCT05536973) for ixo-vec is already underway, with the first patient having been dosed in September of this year.2

“We are pleased to present our final 2-year analysis from our OPTIC trial of Ixo-vec for the treatment of wet AMD,” Richard Beckman, MD, chief medical officer, Adverum Biotechnologies, said in a statement.1 “Ixo-vec demonstrated a robust treatment effect while maintaining a favorable safety profile, particularly at the 2x1011 dose which was advanced to our Phase 2 LUNA trial. We are particularly encouraged by the continuous and consistent aflibercept protein levels, through 3 years, as well as the maintenance to improvement in BCVA and CST from baseline while dramatically reducing the anti-VEGF treatment burden for patients. The longer-term follow-up data from OPTIC further strengthens our confidence in the design of the ongoing LUNA trial where we are evaluating the 2x1011 dose and a new, lower 6x1010 dose, along with enhanced prophylactic steroid regimens.”

Ixo-vec uses AAV.7m8, a proprietary vector capsid, and can be administered in a single-dose via intravitreal injection in a physician’s office setting.2 It was previously investigated in a phase 2 clinical trial (INFINITY; NCT04418427) for diabetic macular edema.3 However, the trial was halted after a serious dose-limiting toxicity was observed, resulting in Adverum no longer pursuing ixo-vec for that indication.

The multicenter, open-label OPTIC trial began on November 14, 2018, and enrolled 30 patients with wet AMD who at the time of enrollment were managing their disease with anti-VEGF injections.1 The trial’s participants were followed for 2 years after treatment with ixo-vec. They were also able to enroll in the ongoing 3-year OPTIC-EXT extension study which will bring the total follow-up for these participants to 5 years.

“The complete data set from the OPTIC trial affirms that Ixo-vec may offer a potentially transformational treatment for wet AMD,” Carl Regillo, MD, FACS, chief of retina services, Wills Eye Hospital, and presenter of the data at The Retina Society’s Annual Meeting, added to the statement.1 “A favorable benefit-risk profile resulting in an 81% reduction in annualized anti-VEGF injections was demonstrated in participants receiving the 2x1011 dose regardless of baseline neutralizing antibodies, 53% of whom were supplemental injection free over 2 years. That is very promising and meaningful to patients, physicians, and the overall healthcare system. I look forward to serving as a LUNA phase 2 investigator and gaining a further understanding of the safety and efficacy profile of Ixo-vec.”

1. Adverum Biotechnologies presents positive end of study results from the OPTIC trial in wet AMD including two-year outcomes following a single intravitreal injection of ixo-vec (ADVM-022). News release. Adverum Biotechnologies, Inc. November 4, 2022. https://investors.adverum.com/news/news-details/2022/Adverum-Biotechnologies-Presents-Positive-End-of-Study-Results-from-the-OPTIC-Trial-in-Wet-AMD-Including-Two-Year-Outcomes-Following-a-Single-Intravitreal-Injection-of-Ixo-vec-ADVM-022/default.aspx 
2. Adverum Biotechnologies announces first subject dosed with ixo-vec in the phase 2 LUNA trial for the treatment of wet age-related macular degeneration. News release. Adverum Biotechnologies, Inc. September 14, 2022. https://investors.adverum.com/news/news-details/2022/Adverum-Biotechnologies-Announces-First-Subject-Dosed-with-Ixo-vec-in-the-Phase-2-LUNA-Trial-for-the-Treatment-of-Wet-Age-Related-Macular-Degeneration/default.aspx
3. Adverum provides update on ADVM-022 and the INFINITY trial in patients with diabetic macular edema. News release. News release. Adverum Biotechnologies. July 22, 2021. https://investors.adverum.com/news/news-details/2021/Adverum-Provides-Update-on-ADVM-022-and-the-INFINITY-Trial-in-Patients-with-Diabetic-Macular-Edema/default.aspx 
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