- FDA issues Complete Response Letter (CRL) for resubmitted ONS-5010 BLA
- Outlook Therapeutics plans to work with FDA to address the Agency’s issues
Outlook Therapeutics, Inc., a biopharmaceutical company focused on enhancing the standard of care for bevacizumab for the treatment of retina diseases, announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) to its biologics license application (BLA) resubmission, indicating that the FDA cannot approve the application in its present form for the treatment of wet age-related macular degeneration (wet AMD).
The CRL included only one deficiency, for a lack of substantial evidence of effectiveness. In the CRL, the FDA advised that, because ONS-5010 did not meet the primary efficacy endpoint in NORSE EIGHT, it is recommended that confirmatory evidence of efficacy be submitted to support the application for ONS-5010. Additionally, the FDA reiterated that NORSE TWO met its primary endpoint for effectiveness.
“While we are very disappointed with this outcome, we intend to meet with the FDA to receive additional clarity on their requirements to potentially approve the first on-label bevacizumab product specifically formulated, manufactured, and packaged for intravitreal use in the United States. We remain committed to providing patients with a safe and effective alternative to compounded Avastin manufactured in the United States,” commented Bob Jahr, CEO of Outlook Therapeutics. “It is important to also note that the CRL identified no other outstanding deficiencies in our BLA.”
In addition to requesting a meeting with the FDA to explore pathways for potential approval in the U.S., Outlook Therapeutics intends to continue its efforts to expand into additional markets in Europe. As previously announced, LYTENAVA (bevacizumab gamma) was granted Marketing Authorization by the European Commission in the EU and Marketing Authorization by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD.
In June 2025, LYTENAVA (bevacizumab gamma) became commercially available in Germany and the UK for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the European Union and UK.
About wet AMD
Age-related macular degeneration, AMD, is a common eye condition and a leading cause of vision loss among people aged 50 and older. It causes damage to the macula, a small spot near the center of the retina and the part of the eye needed for sharp, central vision, which lets us see objects that are straight ahead. Wet AMD, a form of late-stage AMD, is also called neovascular AMD.
In wet AMD, abnormal blood vessels grow underneath the retina. These vessels leak fluid and blood, which may lead to swelling and damage to the macula, causing vision loss. Additionally, with wet AMD, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted in the eyes. VEGF is a protein that promotes the growth of new abnormal blood vessels; anti-VEGF injection therapy blocks this growth and has become the standard-of-care treatment for wet AMD and other retinal diseases, such as diabetic macular edema and branch retinal vein occlusion.
About ONS-5010/LYTENAVA (bevacizumab-vikg, bevacizumab gamma)
ONS-5010/LYTENAVA™ is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the EU and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD.
In the United States, ONS-5010/LYTENAVA (bevacizumab-vikg) is investigational. In certain European Union Member States ONS-5010/LYTENAVA™ must receive pricing and reimbursement approval before it can be sold.
Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.
About Outlook Therapeutics, Inc.
Outlook Therapeutics is a biopharmaceutical company focused on the development and commercialization of ONS-5010/LYTENAVA (bevacizumab-vikg, bevacizumab gamma) to enhance the standard of care for bevacizumab for the treatment of retina diseases. LYTENAVA (bevacizumab gamma) is the first ophthalmic formulation of bevacizumab to receive European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics commenced commercial launch of LYTENAVA (bevacizumab gamma) in Germany and the UK as a treatment for wet AMD.
In the United States, ONS-5010/LYTENAVA (bevacizumab-vikg) is investigational. If approved in the United States, ONS-5010/LYTENAVA, would be the first approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD.