New Study Planned for Bevacizumab to Treat AMD

Outlook Therapeutics plans to conduct a three-month non-inferiority study for its ophthalmic formulation of bevacizumab to treat patients with wet age-related macular degeneration (AMD). The company has submitted to the FDA a special protocol assessment for Lytenava (bevacizumab-vikg) and plans to begin the study in the first quarter of 2024.

Lytenava, also known as ONS-5010, is an ophthalmic formulation of bevacizumab for intravitreal injection. If approved, it would be the only bevacizumab product to specifically treat age-related macular degeneration. Currently, bevacizumab is used off-label to treat wet age-related macular degeneration and must be obtained from compounding pharmacies. These pharmacies repackage small quantities of bevacizumab into syringes for intravitreal injection, which is placed in the space in the back of the eye.

Bevacizumab is a recombinant humanized monoclonal antibody that is a vascular endothelial growth factor (VEGF) inhibitor, which blocks blood vessel growth. The product is available as Avastin to treat cancers such as colorectal, lung, glioblastoma, kidney, cervical and ovarian cancer. In age-related macular degeneration, bevacizumab is thought to prevent the interaction of VEGF with its receptors on the surface of endothelial cells, reducing new blood vessel formation in the retina.

The additional trial that Outlook Therapeutics is conducting, NORSE EIGHT, will be a controlled, masked study of neovascular age-related macular degeneration patients randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Patients will receive injections at day 0, week 4, and week 8 visits. About 400 patients are expected to be enrolled in the study.

Russell Trenary

“Based on our ongoing discussions with FDA, we believe we have agreement on a clinical trial protocol,” Russell Trenary, president and CEO Outlook Therapeutics, said in a press release.

Outlook Therapeutics expects to resubmit the biologics license application by the end of calendar year 2024 to include the results of NORSE EIGHT, as well as additional chemistry, manufacturing and control (CMC) to address issues the FDA had indicated in its complete response letter in August 2023.

Related: FDA Issues CRL for Bevacizumab to Treat Wet AMD

In its complete response letter, regulators indicated that there were issues related to quality, preapproval manufacturing inspections, and a lack of substantial evidence. Company officials met with the FDA to design a trial to meet the agency’s requirements and they have identified the CMC issues that need to be resolved.