Outlook Therapeutics Provides Regulatory Update on U.S. Food and Drug Administration Review of ONS-5010/LYTENAVA™ (bevacizumab-vikg) for the Treatment of Wet AMD

Rhea-AI Summary

Outlook Therapeutics (Nasdaq: OTLK) said the U.S. Food and Drug Administration issued a Complete Response Letter (CRL) for the resubmitted biologics license application for ONS-5010/LYTENAVA (bevacizumab-vikg) for wet age-related macular degeneration (wet AMD), indicating the application cannot be approved in its present form.

The FDA noted one adequate and well-controlled study demonstrated efficacy but again requested confirmatory evidence of efficacy and did not specify what evidence would be acceptable. The resubmission was based on the NORSE clinical program (including NORSE TWO and NORSE EIGHT).

Outlook said it is exploring U.S. approval pathways and continuing commercial expansion in Europe, where LYTENAVA received European Commission and MHRA marketing authorizations and became commercially available in Germany and the UK in June 2025.

Positive

• NORSE TWO pivotal study demonstrated efficacy
• European Commission granted marketing authorization for LYTENAVA
• MHRA granted marketing authorization for LYTENAVA
• Commercial availability in Germany and UK from June 2025

Negative

• FDA issued a CRL and will not approve the BLA in its present form
• FDA requested confirmatory evidence of efficacy and did not specify acceptable evidence

Key Figures

NORSE EIGHT duration: 12-week study Primary endpoint timing: 8 weeks CRL status: Complete Response Letter +1 more

4 metrics

NORSE EIGHT duration 12-week study Adequate and well-controlled non-inferiority trial of ONS-5010 vs ranibizumab

Primary endpoint timing 8 weeks Primary efficacy endpoint in NORSE EIGHT treatment-naïve patients

CRL status Complete Response Letter FDA could not approve current ONS-5010 BLA resubmission for wet AMD

Price move -5.81% Move against prior close before publication of this CRL update

Market Reality Check

Vol: Volume 5,705,336 is 1.58x...

high vol

Volume Volume 5,705,336 is 1.58x the 20-day average of 3,613,816, indicating elevated trading interest ahead of this update. high

Technical Price at $1.87 is trading above the 200-day moving average at $1.63, despite the negative regulatory outcome.

Peers on Argus

OTLK was down 5.81% while close peers showed mixed, smaller moves (some modest g...

OTLK was down 5.81% while close peers showed mixed, smaller moves (some modest gains, others declines), indicating today’s move was largely stock-specific rather than a broad biotech reaction.

Historical Context

5 past events · Latest: Dec 26 (Neutral)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 26	Inducement grants	Neutral	+8.8%	Stock options granted to new employees as inducement awards.
Dec 19	Full-year earnings	Negative	-2.9%	Reported sizeable net loss with modest initial LYTENAVA revenue and low cash.
Nov 24	Conference appearance	Neutral	-4.3%	Participation in a healthcare conference and investor meetings.
Nov 13	FDA acceptance	Positive	+14.8%	FDA accepted ONS-5010 BLA resubmission and set a PDUFA date.
Nov 03	BLA resubmission	Positive	+3.2%	Re-submission of ONS-5010 BLA after addressing prior CRL issues.

Pattern Detected

Recent FDA milestones for ONS-5010 had generally drawn positive share-price reactions, while earnings and corporate updates saw smaller, mixed moves. Today’s negative CRL contrasts with the earlier favorable sentiment around the resubmission and acceptance of the BLA.

Recent Company History

Over the last two months, Outlook Therapeutics has focused on regulatory progress for ONS-5010 and building its European commercial presence. The BLA resubmission on Nov 3, 2025 and subsequent FDA acceptance with a Dec 31, 2025 PDUFA date were key milestones that previously coincided with positive stock reactions. An earnings update highlighted a $62.4M net loss and initial European LYTENAVA revenue. Today’s Complete Response Letter reverses the prior constructive U.S. regulatory narrative and shifts near-term focus back to alternative approval pathways and ex-U.S. markets.

Market Pulse Summary

This announcement details the FDA’s Complete Response Letter for the ONS-5010 BLA resubmission, sign...

Analysis

This announcement details the FDA’s Complete Response Letter for the ONS-5010 BLA resubmission, signaling that current data are insufficient for U.S. approval in wet AMD. The FDA requested confirmatory efficacy evidence but has not defined a preferred approach. In contrast, LYTENAVA already holds Marketing Authorizations in the EU and UK and launched in June 2025. Investors may focus on how Outlook Therapeutics pursues additional U.S. data, progresses ex-U.S. launches, and communicates any updated clinical or regulatory plans.

Key Terms

complete response letter, biologics license application, wet age-related macular degeneration, non-inferiority study, +2 more

6 terms

complete response letter regulatory

"FDA has issued a complete response letter (CRL) to the ONS-5010..."

A complete response letter is an official communication from a drug or medical-device regulator, such as the U.S. Food and Drug Administration (FDA), telling a company that a marketing application cannot be approved in its current form and listing the specific deficiencies to be fixed. For investors it matters because it pauses or delays a product’s path to market—like a building inspector issuing a list of repairs before a certificate of occupancy—affecting revenue timing, costs and stock value.

biologics license application regulatory

"biologics license application (BLA) resubmission, indicating that the FDA..."

A biologics license application is a formal request submitted to regulatory authorities seeking approval to market a new biological medicine, such as vaccines or treatments made from living organisms. It is a comprehensive review process that evaluates the safety, effectiveness, and manufacturing quality of the product. For investors, receiving approval signals that a biological therapy can be sold to the public, potentially leading to revenue growth and market success.

wet age-related macular degeneration medical

"for the treatment of wet age-related macular degeneration (wet AMD)."

A severe eye condition in which abnormal, fragile blood vessels grow beneath the macula — the small central part of the retina responsible for sharp, detailed vision — and leak fluid or blood, causing rapid loss of central sight. Investors care because the condition drives demand for high-cost therapies, medical devices and ongoing care; successful treatments can create sizable markets, affect healthcare spending and influence regulatory and reimbursement decisions, much like fixing a leaking camera lens restores image quality and value.

non-inferiority study medical

"NORSE EIGHT, an adequate and well-controlled non-inferiority study evaluating..."

A non-inferiority study is a clinical trial designed to show a new drug or medical treatment is not meaningfully worse than an existing standard treatment on a key outcome. Think of it like proving a new smartphone model has battery life close enough to the current leader so most users wouldn’t notice a loss; success can be enough for regulators to approve and for doctors to adopt it. For investors, positive results reduce regulatory and commercial risk, support market access and pricing strategies, and can unlock revenue growth without needing to beat established therapies outright.

intravitreal use medical

"specifically formulated, manufactured, and packaged for intravitreal use,” commented..."

Intravitreal use means delivering a medicine directly into the eye’s vitreous — the clear, gel-like center — usually by a small injection into the eyeball. For investors this matters because the route affects how well a drug reaches its target, its safety profile, regulatory requirements, administration setting (clinic versus at-home), and the likely frequency of treatment, all of which influence clinical success, cost and commercial potential.

marketing authorization regulatory

"was granted Marketing Authorization by the European Commission in the EU..."

An official government approval that allows a drug, vaccine, or medical device to be sold and promoted in a specific country or region. Think of it as a safety and effectiveness passport issued after regulators review the product’s tests and manufacturing; for investors, receiving this authorization typically unlocks sales, revenue potential, and lower regulatory risk, while delays or denials can substantially affect a company’s value and timeline.

AI-generated analysis. Not financial advice.

FDA issues Complete Response Letter (CRL) for resubmitted ONS-5010 BLA

ISELIN, N.J., Dec. 31, 2025 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on enhancing the standard of care for bevacizumab for the treatment of retina diseases, today announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) to the ONS-5010/LYTENAVA™ (bevacizumab-vikg) biologics license application (BLA) resubmission, indicating that the FDA cannot approve the application in its present form for the treatment of wet age-related macular degeneration (wet AMD).

In the CRL, the FDA noted that the additional mechanistic and natural history data information provided in the BLA resubmission does not alter the previous review conclusion that while the one adequate and well-controlled study demonstrated efficacy, the FDA has again recommended that confirmatory evidence of efficacy be submitted to support the application, however the FDA has not indicated what type of confirmatory evidence would be acceptable.

“Our goal has always been to provide wet AMD patients and their physicians with a safe, consistent, FDA-approved alternative to compounded Avastin manufactured in the United States, and that goal has not changed. 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. We continue to believe strongly in the clinical need and commercial potential of the first on-label bevacizumab product for patients in the United States that is specifically formulated, manufactured, and packaged for intravitreal use,” commented Bob Jahr, Chief Executive Officer of Outlook Therapeutics.

The ONS-5010 BLA resubmission was based on the complete data set from the NORSE clinical trial program, which included the successful NORSE TWO adequate and well-controlled pivotal clinical trial as well as confirmatory safety and efficacy data from all other NORSE trials, including NORSE EIGHT, an adequate and well-controlled 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. Outlook Therapeutics continues to believe that the complete data set for NORSE TWO, 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.

Outlook Therapeutics is currently exploring all available pathways for potential approval in the U.S. and intends to continue its efforts to expand into additional markets in Europe and other regions. As previously announced, LYTENAVA™ (bevacizumab gamma) was granted Marketing Authorization by the European Commission in the EU and Marketing Authorization by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD. In June 2025, LYTENAVA™ (bevacizumab gamma) became commercially available in Germany and the UK for the treatment of wet AMD. In addition to current plans to expand its commercial presence in select countries in Europe, Outlook Therapeutics continues to speak with and explore collaborations with potential commercial and distribution partners in additional European countries, as well as outside of Europe. LYTENAVA™ (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the European Union and UK.

About Wet AMD

Age-related macular degeneration, AMD, is a common eye condition and a leading cause of vision loss among people aged 50 and older. It causes damage to the macula, a small spot near the center of the retina and the part of the eye needed for sharp, central vision, which lets us see objects that are straight ahead. Wet AMD, a form of late-stage AMD, is also called neovascular AMD.

In wet AMD, abnormal blood vessels grow underneath the retina. These vessels leak fluid and blood, which may lead to swelling and damage to the macula, causing vision loss. Additionally, with wet AMD, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted in the eyes. VEGF is a protein that promotes the growth of new abnormal blood vessels; anti-VEGF injection therapy blocks this growth and has become the standard-of-care treatment for wet AMD and other retinal diseases, such as diabetic macular edema and branch retinal vein occlusion.

About ONS-5010 / LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma)

ONS-5010/LYTENAVA™ is an ophthalmic formulation of bevacizumab produced in the United States for the treatment of wet AMD. LYTENAVA™ (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the EU and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD.

In the United States, ONS-5010/LYTENAVA ™ (bevacizumab-vikg) is investigational. In certain European Union Member States ONS-5010/LYTENAVA™ must receive pricing and reimbursement approval before it can be sold.

Bevacizumab-vikg (bevacizumab gamma in the EU and UK) 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. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

About Outlook Therapeutics, Inc.

Outlook Therapeutics is a biopharmaceutical company focused on the development and commercialization of ONS-5010/LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma) to enhance the standard of care for bevacizumab for the treatment of retina diseases. LYTENAVA™ (bevacizumab gamma) is the first ophthalmic formulation of bevacizumab to receive European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics commenced commercial launch of LYTENAVA™ (bevacizumab gamma) in Germany and the UK as a treatment for wet AMD.

In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational. If approved in the United States, ONS-5010/LYTENAVA™, would be the first approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD.

Forward-Looking Statements

This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “expect,” “may,” “on track,” “plan,” “potential,” “target,” “will,” or “would” the negative of terms like these or other comparable terminology, and other words or terms of similar meaning. These include, among others, plans for commercial launch of LYTENAVA™ in additional markets and the timing thereof, expectations concerning decisions of regulatory bodies and the timing thereof, including market exclusivity, the future potential to receive approval from the FDA and the timing thereof, the potential of ONS-5010/LYTENAVA™ as a treatment for wet AMD, the market opportunity for LYTENAVA™ in Europe, the United States and other countries, the ability to successfully launch directly or via partnerships with other companies, and other statements that are not historical fact. Although Outlook Therapeutics believes that it has a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting Outlook Therapeutics and are subject to risks, uncertainties, and factors relating to its operations and business environment, all of which are difficult to predict and many of which are beyond its control. These risk factors include those risks associated with developing and commercializing pharmaceutical product candidates, including the risk that the data from the NORSE EIGHT trial does not support the approval by the FDA of the ONS-5010 BLA, the content and timing of decisions by regulatory bodies, the acceptance of Outlook Therapeutics’ products by healthcare professionals and patients as safe, effective, and cost-effective, the impact of governmental and semi-governmental laws, regulations and guidelines, reliance on third-party service providers, suppliers, and manufacturers, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals, the content and timing of decisions by regulatory bodies, the sufficiency of Outlook Therapeutics’ resources, as well as those risks detailed in Outlook Therapeutics’ filings with the Securities and Exchange Commission (the SEC), including the Annual Report on Form 10-K for the fiscal year ended September 30, 2025, filed with the SEC on December 19, 2025, as supplemented by future reports Outlook Therapeutics files with the SEC, which include uncertainty of market conditions and future impacts related to macroeconomic factors, including as a result of the ongoing overseas conflicts, tariffs and trade tensions, fluctuations in interest rates and inflation and potential future bank failures on the global business environment. These risks may cause actual results to differ materially from those expressed or implied by forward-looking statements in this press release. All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Outlook Therapeutics does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law.

Investor Inquiries:
Jenene Thomas
Chief Executive Officer
JTC Team, LLC
T: 908.824.0775
OTLK@jtcir.com

FAQ

What did Outlook Therapeutics announce about ONS-5010/LYTENAVA and the FDA on December 31, 2025?

The company announced the FDA issued a Complete Response Letter saying the BLA cannot be approved in its present form and requested confirmatory efficacy evidence.

Does the FDA say any trial showed efficacy for ONS-5010 (OTLK)?

The FDA noted that one adequate and well-controlled study demonstrated efficacy, per the CRL.

What clinical data supported the ONS-5010 BLA resubmission for OTLK?

The resubmission relied on the complete NORSE clinical program, including the pivotal NORSE TWO trial and NORSE EIGHT confirmatory data.

Is LYTENAVA approved or available in Europe for wet AMD?

Yes; LYTENAVA received European Commission and MHRA authorizations and was commercially available in Germany and the UK in June 2025.

What next steps did Outlook Therapeutics (OTLK) say it will pursue after the CRL?

The company said it is exploring all available U.S. approval pathways and continuing to expand commercial efforts and partner discussions in Europe and other regions.