At a Glance
- FDA issued a CRL citing lack of substantial evidence of effectiveness
- Outlook Therapeutics has requested a Type A meeting with the FDA
- NORSE TWO Phase 3 trial met primary visual acuity endpoint
- LYTENAVA™ already approved and launched in the EU and UK
Written By: Pharmacally Medical News Desk
Outlook Therapeutics, Inc. has submitted a Type A meeting request to the U.S. Food and Drug Administration (FDA) following receipt of a Complete Response Letter (CRL) dated December 30, 2025, concerning its Biologics License Application (BLA) for ONS-5010 / LYTENAVA™ (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).
CRL and Company Position
The CRL identified a single issue, citing a lack of substantial evidence of effectiveness and recommending the submission of additional confirmatory clinical data. Outlook Therapeutics stated that the agency’s conclusion was unexpected and inconsistent with the evidence included in its BLA.
The company emphasized that the application contains results from an adequate and well-controlled Phase 3 trial, along with supportive confirmatory data. Outlook also noted that prior discussions with the FDA in September 2025 had aligned on the requirements for resubmission, prompting the company to engage in informal meetings with the agency before requesting the Type A meeting.
Clinical Evidence Base
The BLA is primarily supported by data from the NORSE TWO trial (NCT03834753), a Phase 3 study that met its primary endpoint, demonstrating a three-line (15-letter) gain in visual acuity at 12 months. Key secondary endpoints, including mean change in visual acuity, were also achieved.
Additional evidence was generated from NORSE EIGHT (NCT06190093), a study conducted at the FDA’s request. While the trial did not meet its primary endpoint at eight weeks, the study demonstrated positive trends in visual acuity through 12 weeks, with outcomes considered consistent with the known anti-VEGF mechanism of action.
Outlook further highlighted supporting data related to VEGF inhibition, pharmacodynamic effects, and comparisons with the natural history of untreated wet AMD, all of which indicated clinically meaningful benefits.
Safety Profile and Clinical Rationale
ONS-5010 demonstrated a safety profile consistent with ranibizumab controls and the broader class of intravitreal anti-VEGF therapies. The company stated that no safety concerns were raised in the CRL or during prior regulatory interactions.
Outlook Therapeutics also positioned LYTENAVA™ as a standardized, FDA-approved alternative to off-label repackaged bevacizumab, supported by U.S.-based manufacturing intended to enhance product quality and supply reliability.
Regulatory and Commercial Context
LYTENAVA™ has already secured regulatory approvals in the European Union and the United Kingdom. The therapy has been commercially available in Germany and the UK since June 2025, with broader European expansion plans underway.
Next Steps
Chief Executive Officer Bob Jahr reiterated the company’s confidence in the clinical data package and its belief that the evidence meets FDA standards for effectiveness. The upcoming Type A meeting is expected to focus on clarifying potential regulatory pathways, including whether the existing dataset may be sufficient to support approval without additional large-scale trials.
A favorable resolution could position ONS-5010 / LYTENAVA™ as a differentiated, approved bevacizumab option for retina specialists in the United States.
Reference
Outlook Therapeutics Submits Type A Meeting Request to FDA Following Complete Response Letter, 11 February 2026, Outlook Therapeutics Submits Type A Meeting Request to FDA Following Complete Response Letter – Outlook Therapeutics, Inc.
FDA Issues Third CRL for Outlook Therapeutics’ ONS-5010/LYTENAVA in Wet AMD – What It Means, 01 January 2026, https://pharmacally.com/fda-issues-third-crl-for-outlook-therapeutics-ons-5010-lytenava-in-wet-amd-what-it-means/
A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects with Neovascular Age-related Macular Degeneration (AMD), ClinicalTrials.gov ID NCT03834753, https://clinicaltrials.gov/study/NCT03834753
A 3-month Study to Assess the Safety and Effectiveness of ONS-5010 in Subjects with Neovascular Age-related Macular Degeneration (AMD), ClinicalTrials.gov ID NCT06190093, https://clinicaltrials.gov/study/NCT06190093