Outlook Therapeutics, Inc. (NASDAQ: OTLK) experienced a steep decline in its stock price on Friday, reaching a fresh 52-week low following the U.S. Food and Drug Administration’s (FDA) issuance of another complete response letter (CRL) concerning its drug application for wet age-related macular degeneration (wet AMD).
The regulatory setback centers on Outlook's biologics license application (BLA) resubmission for ONS-5010, marketed as Lytenava (bevacizumab-vikg). The FDA has determined that the data presented are insufficient to approve the treatment for wet AMD in its present form.
Wet AMD is a serious ocular condition characterized by the abnormal proliferation of blood vessels beneath the retina, leading to leakage of blood and fluid, which results in accelerated central vision loss. Patients often experience distorted vision manifested by wavy lines, dark spots, or blurred areas within their central field of view.
Looking back at the regulatory history, in August 2025, the FDA previously issued a complete response letter to Outlook Therapeutics’ resubmission of the ONS-5010 application. The deficiency cited was primarily related to the lack of substantial evidence supporting the medication’s effectiveness.
Similarly, in August 2023, Outlook Therapeutics first received a CRL from the FDA, with the agency underscoring that the additional mechanistic and natural history data supplied in the BLA resubmission did not change the prior conclusion from their initial review.
The recent CRL reaffirms the FDA’s standing position that, despite the presence of at least one well-controlled study demonstrating some efficacy, there remains a need for confirmatory evidence before approval can be granted. The FDA has not, however, provided specific guidance on the nature or type of confirmatory evidence that would meet their standards.
The resubmitted application made use of the comprehensive data collected from the NORSE clinical trial program, which assessed ONS-5010’s safety and efficacy. Nonetheless, this was insufficient to sway regulatory acceptance.
In response to these regulatory hurdles, Outlook Therapeutics has indicated that it is actively evaluating all potential pathways to secure approval within the United States market. Concurrently, the company plans to pursue expansion efforts targeting markets in Europe and other international regions.
Within the wider industry context, other biopharmaceutical companies have encountered similar obstacles. For instance, in March 2025, Opthea Limited (NASDAQ: OPT) reported that its global Phase 3 COAST trial for wet AMD did not achieve the primary endpoint evaluating mean change in best corrected visual acuity (BCVA) from baseline to week 52. This trial investigated intravitreal administration of 2 mg sozinibercept every four to eight weeks in combination with 2 mg doses of Regeneron Pharmaceuticals Inc.’s (NASDAQ: REGN) Eylea (aflibercept) given every eight weeks after a loading period.
Reflecting market reaction, Outlook Therapeutics shares were off sharply during premarket trading on Friday, declining approximately 60.82% to a price near $0.61, according to financial data aggregator Benzinga Pro. This drop marks the stock’s lowest trading level for the past year.
As Outlook Therapeutics confronts significant regulatory challenges with its Lytenava application, the uncertainty surrounding approval timelines and evidence requirements remains elevated. The company’s commitment to exploring alternative approval routes and global market opportunities may provide some diversification, but immediate U.S. prospects appear constrained.