FDA Announces Goal Date for Resubmitted Bevacizumab to Treat Wet AMD

The FDA has accepted the resubmission of Outlook Therapeutics’ biologics license application (BLA) for ONS-5010 (bevacizumab-vikg), an ophthalmic formulation of bevacizumab to treat patients with wet age-related macular degeneration (wet AMD). The FDA set a Prescription Drug User Fee Act (PDUFA) goal date of Aug. 27, 2025. If approved, the therapy would be branded as Lytenava and is expected to receive 12 years of regulatory exclusivity.

The FDA had issued a complete response letter (CRL) for ONS-5010 in August 2023. Regulators at the time had said there were issues related to quality, preapproval manufacturing inspections, and a lack of substantial evidence.

Outlook Therapeutics had resubmitted the application in February 2025. The company had said previously that in order to meet the FDA’s requirement for a second adequate and well-controlled clinical trial of ONS-5010, it could conduct a non-inferiority study evaluating ONS-5010 versus ranibizumab in a 12-week study of treatment-naïve patients with a primary efficacy endpoint at 8 weeks (the NORSE EIGHT study).

The ONS-5010 BLA resubmission was based on the efficacy and safety demonstrated in NORSE EIGHT, as well as additional chemistry, manufacturing, and controls (CMC) information requested by the FDA.

Company executives said they believe that the complete data set for NORSE EIGHT and the additional CMC information in the BLA resubmission, combined with the data from the other NORSE clinical trials, provides the required evidence to support approval of the ONS-5010 BLA in the United States.

NORSE EIGHT was a randomized, non-inferiority study of 400 newly diagnosed, wet AMD patients who received either 1.25 mg ONS-5010 or 0.5 mg Lucentis (ranibizumab) intravitreal injections. The primary endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 8.

In November 2024, Outlook Therapeutics reported that in NORSE EIGHT, ONS-5010 demonstrated a mean 4.2-letter improvement in best corrected visual acuity but that it did not meet the pre-specified non-inferiority endpoint at week 8 in the special protocol assessment with the FDA.

In January 2025, Outlook Therapeutics announced results from the completed analysis of the 12-week safety and efficacy results for NORSE EIGHT, which indicated that ONS-5010 demonstrated clinically meaningful anatomic and functional improvements at each study timepoint.

Results from the 12-week analysis demonstrated a mean improvement in BCVA of 3.3 to 5.5 letters in the ONS-5010 arm across the 4, 8, and 12-week timepoints, compared with a mean 4.5 to 6.5 letter improvement in the ranibizumab arm over the same timepoints. These data were presented at the Hawaiian Eye and Retina 2025 Meeting in January 2025.

Baruch D. Kuppermann, M.D., Ph.D.

“The NORSE EIGHT results provide additional evidence to the retina community that ONS-5010 meets the expectations for an ophthalmic formulation of bevacizumab, without the challenges that can arise from using repackaged, off-label formulations available today,” Baruch D. Kuppermann, M.D., Ph.D., of theGavin Herbert Eye Institute, University of California, said in a news release at the time.

Kuppermann said the reductions in central retinal thickness observed in the trial confirmed that ONS-5010 reduced fluid in the retina on par with ranibizumab. “I’ve been encouraged with the consistency of this treatment across all NORSE clinical studies,” he said.

Age-related macular degeneration occurs when the macula, part of the retina at the back of the eye, becomes damaged. About 10% of all cases become wet, which leads to vision loss as a result of excess blood vessel growth between two layers of cells in the retina. It is also called neovascular AMD.

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. It is used off-label to treat wet AMD. In addition, several Avastin biosimilars have been approved, including Mvasi, Zirabev, Alymsys, Vegzelma and Avzivi.

ONS-5010 is an ophthalmic formulation of bevacizumab for intravitreal injection, which is placed in the space in the back of the eye. If approved, it would be the only bevacizumab product to specifically treat AMD. Currently, bevacizumab must be obtained from compounding pharmacies to be used in the eye. These pharmacies repackage small quantities of bevacizumab into syringes for intravitreal injection.