Outlook Therapeutics resubmitted its Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for ONS-5010, an investigational ophthalmic product. If approved, it will be branded as LYTENAVA (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD), the company said in a press release. 

The ONS-5010 BLA resubmission is based on the efficacy and safety demonstrated in NORSE EIGHT, as well as additional chemistry, manufacturing and controls (CMC) information requested by the FDA, the company said. As previously announced, following Type A meetings with the FDA in Q4 CY2023 to address the ONS-5010 Complete Response Letter, the FDA informed Outlook Therapeutics 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 vs ranibizumab in a 12-week study of treatment naïve patients with a primary efficacy endpoint at 8 weeks (NORSE EIGHT).

Outlook Therapeutics said it believes 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. A decision from the FDA is expected within 6 months.

NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 / LYTENAVA or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint is 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 BCVA, which did not meet the pre-specified non-inferiority endpoint at week 8 set forth 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. BCVA data across all study timepoints demonstrated an improvement in vision, increasing over time, and the presence of biologic activity. 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 measured in the study, compared to a mean 4.5 to 6.5 letter improvement in the ranibizumab arm over the same timepoints.

Additionally, the complete NORSE EIGHT data set showed that anatomical response was similar between treatments, with a reduction in central retinal thickness of -123.9 microns for ONS-5010 treated eyes and -127.3 microns for the ranibizumab group, virtually no difference between the arms. 

“We remain committed to bringing an ophthalmic bevacizumab to market in the United States and providing retina patients suffering from wet AMD with a much needed treatment option that has the potential to address the problems associated with unapproved repackaged bevacizumab," said Lawrence Kenyon, chief financial officer and interim chief executive officer of Outlook Therapeutics, in the press release. "Our team has worked diligently to address the FDA’s requests and we believe this resubmission provides the necessary evidence to support approval of the ONS-5010 BLA in the United States. This resubmission marks a very significant milestone and puts us another step closer to a transformed Outlook Therapeutics.”