On December 31 2025, the U.S. Food and Drug Administration issued a Complete Response Letter (CRL) to Outlook Therapeutics, Inc. for its biologics license application (BLA) for ONS‑5010, the company’s ophthalmic bevacizumab intended to treat wet age‑related macular degeneration (wet AMD). The CRL states that the data submitted in the resubmission do not alter the agency’s prior conclusion that confirmatory evidence of efficacy is required, meaning the drug will not receive U.S. approval in its current form and the company must submit additional evidence before a future review.
The CRL is the third such rejection for ONS‑5010. The first CRL in August 2023 cited chemistry, manufacturing, and controls (CMC) issues and a lack of substantial evidence, while the second in August 2025 highlighted insufficient evidence of effectiveness and called for more confirmatory efficacy data. The repeated pattern signals a persistent regulatory hurdle that could delay or derail the U.S. launch, a market Outlook estimates to be worth billions of dollars if the drug gains approval.
Outlook’s financial performance in the fiscal year ended September 30 2025 reflects the impact of these regulatory setbacks. The company reported a net loss of $62.4 million, an improvement from the $75.4 million loss in the prior year, and generated its first revenue of $1.4 million from sales of LYTENAVA in Germany and the United Kingdom. The modest revenue growth underscores the company’s reliance on its European launch while the loss margin highlights the high cost of development and the lack of U.S. sales revenue.
Following the CRL, Outlook’s market capitalization fell by approximately $169 million, and the stock price dropped between 62 % and 80 % in after‑hours trading. The sharp decline reflects investor concern that the repeated rejections will erode the company’s ability to secure the critical U.S. approval that underpins its long‑term revenue potential.
CEO Bob Jahr said, “Our goal has always been to provide patients with wet AMD and their physicians with a safe, consistent, FDA‑approved alternative to compounded Avastin manufactured in the United States. We are disappointed and disagree with this decision, but we remain fully committed to taking all necessary steps to receive approval in the United States.” The statement signals the company’s resolve but also acknowledges the setback.
Dr. David A. Eichenbaum, MD, FASRS, cautioned that the repeated CRLs make U.S. approval unlikely without a new, well‑designed trial such as NORSE EIGHT producing a positive outcome. His assessment highlights the high bar the FDA will set for confirmatory evidence and the potential need for additional investment in clinical development.
The CRL’s implications are twofold. First, the U.S. market is a key revenue driver for Outlook; without approval, the company’s growth prospects are severely constrained. Second, the company’s financial health is already fragile, with negative operating margins and a distressed Altman Z‑Score. The regulatory setback amplifies the risk profile, potentially limiting future funding opportunities and increasing the likelihood of a capital‑raising event or strategic partnership to shore up cash reserves.
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