Advancing Novel Gene Therapies

We are advancing a pipeline of gene therapy product candidates targeting the treatment of ocular diseases.

Programs

Wet AMD

ADVM-022 for Wet AMD

For wet AMD, we are advancing our gene therapy candidate ADVM-022 (AAV.7m8-aflibercept) in the OPTIC Phase 1 clinical trial. The multi-center, open-label, Phase 1, dose-ranging trial is designed to assess the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in treatment-experienced patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. For more information on this trial, please visit www.clinicaltrials.gov.

ADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance and improve vision outcomes for wet AMD patients.

In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for ADVM-022 for the treatment of wet AMD.

About Wet AMD

Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the region of the retina at the back of the eye responsible for central vision. In patients with wet AMD, an aggressive form of AMD, abnormal blood vessels grow underneath and into the retina. These abnormal blood vessels leak fluid and blood into and beneath the retina, causing vision loss.

Wet AMD is a leading cause of vision loss in patients over 60 years of age, with a prevalence of approximately 1.2 million individuals in the U.S. and 3 million worldwide1. The incidence of new cases of wet AMD in the U.S. is approximately 150,000 to 200,000 annually, and this number is expected to grow significantly as the country’s population ages2,3.

Although the underlying molecular causes of wet AMD are not completely known, VEGF is known to play a central role in the growth of new blood vessels in wet AMD.

The current standard-of-care therapies for wet AMD are proteins that bind VEGF and neutralize its activity. These therapies can be burdensome, as patients generally require chronic intravitreal injection of anti-VEGF protein every 4-12 weeks. Compliance with this regimen can be difficult for patients and their caregivers, leading to compliance deficiencies and loss of vision from underdosing. It is estimated that these standard-of-care branded anti-VEGF therapies used for the treatment of wet AMD, DR, retinal vein occlusion, and other ocular diseases generated in excess of $11 billion in sales worldwide in 20194.

ADVM-022 gene therapy candidate utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. The OPTIC Phase 1 clinical trial of ADVM-022 in treatment-experienced patients with wet AMD is ongoing.

Resources for wAMD

References:

  1. Arch Ophthalmol. 2004;122(4):564-572. doi:10.1001/archopht.122.4.564.
  2. Brown GC, Brown MM, Sharma S, et al. The Burden of Age-Related Macular Degeneration: A Value-Based Medicine Analysis. Transactions of the American Ophthalmological Society. 2005.
  3. California Retina Consultants. Advances in Wet AMD. Available at: https://www.californiaretina.com/advances-in-wet-amd/
  4. Year-end 2019 financial statements from Regeneron, Roche, and Novartis.

Diabetic Macular Edema (DME)

ADVM-022 for DME

Based on the promising results from the OPTIC Phase 1 clinical trial of ADVM-022 in patients with wet AMD, we advancing our novel gene therapy for the treatment of diabetic macular edema (DME), an ocular disease that also is driven by vascular endothelial growth factor. We are conducting INFINITY, which is a Phase 2, multi-center, randomized, double-masked, active comparator-controlled trial designed to assess a single intravitreal (IVT) injection of ADVM-022 in patients with diabetic macular edema (DME), the most common cause of vision loss in patients with DR.

The INFINITY trial will enroll approximately 33 patients and is designed to demonstrate superior control of disease activity following a single IVT injection of ADVM-022 compared to a single aflibercept injection, as measured by time to worsening of DME disease activity. Additional objectives include assessments of treatment burden, visual acuity, retinal anatomy and safety outcomes.

Across the United States, leading retinal clinical trial sites will participate in the INFINITY trial. For additional information, please visit www.clinicaltrials.gov or www.INFINITYclinicaltrial.com.

ADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance and improve vision outcomes for patients with DME.

About Diabetic Macular Edema (DME)

Over 30 million people are impacted by diabetes in the United States1. Diabetic retinopathy (DR) affects approximately one in three adults with diabetes and can put patients at risk of vision loss. DR can be diagnosed at different severity levels, and is the most common cause of blindness in working-age adults in the U.S.

Diabetic macular edema (DME) is a vision-threatening complication of DR that can occur at any severity stage of DR. DME is characterized by retinal thickening in the area of the macula, and the risk of DME increases with the worsening of the DR severity score (DRSS). DME affects approximately 5% of people with diabetes and is the leading cause of vision loss in patients with DR.

The current standard-of-care therapy for DME is anti-VEGF intravitreal injections. These are effective but typically require frequent and long-term injections for patients to maintain good vision. Compliance with these regimens can be difficult for patients, leading to undertreatment and vision loss. Real-world outcomes in DME with anti-VEGF therapy are meaningfully worse than in clinical trials.

Resources for Diabetic Retinopathy