Outlook Therapeutics resubmits BLA for ONS-5010 for treatment of wet AMD

Outlook Therapeutics has re-submitted its Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for ONS-5010 (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).

Bevacizumab-vikg 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. If approved, the drug will be branded as LYTENAVA.¹

Lawrence Kenyon, chief financial officer and interim CEO of Outlook Therapeutics commented on the resubmission in a press release from the company.¹

“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. 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,” said Kenyon. “This resubmission marks a very significant milestone and puts us another step closer to a transformed Outlook Therapeutics.”

In August of 2023, the FDA issued a complete response letter (CRL)² to Outlook for the company’s BLA of ONS-5010. According to the company, the FDA determined it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

The 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. During a Type A meeting with the FDA,³ the organization informed Outlook 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 (Norse Eight). The company stated that the data provided “provides the required evidence to support approval of the ONS-5010 BLA in the United States.”

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 or 0.5 mg ranibizumab intravitreal injections.The company reported that in the trial, ONS-5010 demonstrated a mean 4.2 letter improvement in best corrected visual acuity (BCVA), which did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the FDA.

However, in January 2025, Outlook Therapeutics announced results from the completed analysis of the 12-week safety and efficacy results for NORSE EIGHT,⁴ which indicated that ONS-5010 demonstrated clinically meaningful anatomic and functional improvements at each study timepoint. According to the company, 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.

A decision from the FDA on the newly resubmitted BLA is expected within 6 months.¹

Reference:

1. Outlook Therapeutics® re-submits biologics license application for ONS-5010 as a treatment for wet AMD to the U.S. Food and Drug Administration. Published February 28, 2025. Accessed February 28, 2025.https://www.globenewswire.com/news-release/2025/02/28/3034713/0/en/Outlook-Therapeutics-Re-Submits-Biologics-License-Application-for-ONS-5010-as-a-Treatment-for-Wet-AMD-to-the-U-S-Food-and-Drug-Administration.html

2. Hutton. D. FDA issues CRL for Outlook Therapeutics’ ONS-5010. Published August 30, 2023. Accessed February 28, 2025. https://www.ophthalmologytimes.com/view/fda-issues-crl-for-outlook-therapeutics-ons-5010

3. Hutton. D. Outlook Therapeutics requests Type A meeting with FDA. Published September 29, 2023. Accessed February 28, 2025. https://www.ophthalmologytimes.com/view/outlook-therapeutics-requests-type-a-meeting-with-fda

4. Harp. M. Outlook Therapeutics completes analysis of 12-week safety and efficacy results of NORSE EIGHT. Published January 16, 2025. Accessed February 28, 2025. https://www.ophthalmologytimes.com/view/outlook-therapeutics-completes-analysis-of-12-week-safety-and-efficacy-results-of-norse-eight