Adverum Biotechnologies Announces IND Active for ADVM-022, a Novel Gene Therapy

Adverum Biotechnologies, Inc. recently announced its Investigational New Drug (IND) application is active for the planned multi-center, open-label, Phase 1, dose-escalation study of ADVM-022, a novel gene therapy candidate for the treatment of wet age-related macular degeneration (wAMD).

“We are excited to have this IND active for ADVM-022, currently the only intravitreal gene therapy candidate entering the clinic for patients with wet AMD,” said Leone Patterson, interim President and Chief Executive Officer of Adverum Biotechnologies. “We have partnered with leading retinal specialists in the U.S. and look forward to initiating the new OPTIC clinical trial in the fourth quarter of this year.”

“We are pleased that we have been able to advance this unique, single-dose treatment into the clinic,” added Mehdi Gasmi, PhD, Chief Science and Technology Officer of Adverum Biotechnologies.“Based on our IND-enabling studies and animal data presented earlier this year at ASGCT, ADVM-022 has the potential to greatly improve the quality of life for patients living with wet AMD.”

The multi-center, open-label, Phase 1, dose-escalation trial is designed to assess the safety and tolerability of a single intravitreal (IVT) injection of ADVM-022 in patients with wAMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. Six leading retinal centers across the US are expected to participate in the Phase 1 trial. The trial is expected to enroll 18 patients and will evaluate three doses of ADVM-022; first dose: 6 x 10^11 vg/eye, second dose: 2 x 10^12 vg/eye, and third dose: 6 x 10^12 vg/eye. Patients will be administered a tapering prophylactic corticosteroid regimen. The primary endpoint of the trial is the safety and tolerability of ADVM-022 at 24 weeks after a single IVT injection. Secondary endpoints include changes in best-corrected visual acuity (BVCA) at 24 weeks, measurement of central retinal thickness (CRT), and number of rescue aflibercept injections. Each patient enrolled will be followed for a total of 2 years.

Adverum’s gene therapy candidate ADVM-022 utilizes a proprietary vector capsid (AAV.7m8) carrying an aflibercept coding sequence under the control of a proprietary expression cassette and is administered as a single intravitreal injection. Excess VEGF activity can lead to wAMD progression and vision loss and current anti-VEGF therapies need to be administered frequently to patients (every 4-12 weeks). Reduced compliance with the current approved regimen is associated with decreased efficacy. Treatment with ADVM-022 is designed to provide potentially sustained therapeutic levels of aflibercept and to minimize the burden of frequent anti-VEGF injections.

In May 2018, long-term preclinical efficacy data on ADVM-022 was presented at the American Society of Gene & Cell Therapy 21st Annual Meeting. In this preclinical study in non-human primate models of wAMD, the efficacy of ADVM-022 at 13 months post-administration was consistent with earlier reported data, demonstrating that single intravitreal injection of ADVM-022 was found to be safe and statistically significant (p<0.0001) in preventing the development of Grade IV lesions compared to the untreated vehicle control group. ADVM-022 induced long-term efficacy that was comparable to aflibercept, an anti- VEGF standard-of-care therapy. In this preclinical study, ADVM-022 was well-tolerated, with no serious adverse events.

In the same preclinical study, ADVM-022 induced sustained intraocular expression of aflibercept for up to 16 months following a single intravitreal injection. Robust levels of aflibercept protein were detected up to 16 months in aqueous and vitreous humor and, more importantly, in retina and choroid tissues, where neovascularization occurs in wAMD.

Adverum is a clinical-stage gene therapy company targeting unmet medical needs in serious rare and ocular diseases. Adverum has a robust pipeline that includes product candidates designed to treat rare diseases alpha-1 antitrypsin (A1AT) deficiency and hereditary angioedema (HAE) as well as wet age-related macular degeneration (wAMD). Leveraging a next-generation adeno-associated virus (AAV)-based directed evolution platform, Adverum generates product candidates designed to provide durable efficacy by inducing sustained expression of a therapeutic protein. Adverum has collaboration agreements with Regeneron Pharmaceuticals to research, develop, and commercialize gene therapy products for ophthalmic diseases and Editas Medicine to explore the delivery of genome editing medicines for the treatment of inherited retinal diseases. Adverum’s core capabilities include clinical development and in-house manufacturing expertise, specifically in process development and assay development. For more information, visit