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
Outlook Therapeutics (NASDAQ: OTLK) announced that the FDA has issued a Complete Response Letter (CRL) for ONS-5010/LYTENAVA™ (bevacizumab-vikg), their wet AMD treatment candidate. The FDA cannot approve the application in its current form due to lack of substantial evidence of effectiveness.
The CRL highlighted that while the NORSE TWO trial met its primary endpoint, the NORSE EIGHT trial did not, leading to the FDA's recommendation for additional confirmatory efficacy evidence. Despite this setback in the U.S., LYTENAVA™ has already received Marketing Authorization in the European Union and UK, and has been commercially available in Germany and UK since June 2025 as the first authorized ophthalmic formulation of bevacizumab for wet AMD treatment.
Outlook Therapeutics (NASDAQ: OTLK) ha comunicato che la FDA ha emesso una Complete Response Letter (CRL) per ONS-5010/LYTENAVA™ (bevacizumab-vikg), il loro candidato terapeutico per la degenerazione maculare umida. La FDA non può approvare la domanda nella forma attuale a causa della mancanza di prove sostanziali di efficacia.
La CRL evidenzia che, sebbene lo studio NORSE TWO abbia raggiunto l'endpoint primario, lo studio NORSE EIGHT non lo ha fatto, e pertanto la FDA richiede ulteriori conferme dell'efficacia. Nonostante questo ostacolo negli USA, LYTENAVA™ ha già ottenuto la autorizzazione alla commercializzazione nell'Unione Europea e nel Regno Unito ed è in vendita in Germania e nel Regno Unito dal giugno 2025 come prima formulazione oftalmica autorizzata di bevacizumab per il trattamento della AMD umida.
Outlook Therapeutics (NASDAQ: OTLK) anunció que la FDA ha emitido una Complete Response Letter (CRL) para ONS-5010/LYTENAVA™ (bevacizumab-vikg), su candidato para la DMAe húmeda. La FDA no puede aprobar la solicitud en su forma actual debido a la falta de evidencia sustancial de eficacia.
La CRL subraya que, aunque el ensayo NORSE TWO cumplió su criterio primario, el NORSE EIGHT no lo hizo, por lo que la FDA recomienda pruebas confirmatorias adicionales de eficacia. A pesar de este revés en EE. UU., LYTENAVA™ ya ha recibido la autorización de comercialización en la Unión Europea y el Reino Unido, y está disponible comercialmente en Alemania y Reino Unido desde junio de 2025 como la primera formulación oftálmica autorizada de bevacizumab para el tratamiento de la DMAe húmeda.
Outlook Therapeutics (NASDAQ: OTLK)는 ONS-5010/LYTENAVA™(bevacizumab-vikg) 건성 아닌 습성 황반변성 치료 후보에 대해 FDA가 Complete Response Letter(CRL)을 발행했다고 발표했습니다. FDA는 효과에 대한 실질적 증거 부족으로 현재 제출된 형태로는 승인할 수 없다고 밝혔습니다.
CRL은 NORSE TWO 시험은 주요 평가변수를 충족했지만 NORSE EIGHT 시험은 충족하지 못해 추가적인 효능 확인 근거를 제시할 것을 권고한다고 지적했습니다. 미국에서의 이 같은 차질에도 불구하고, LYTENAVA™는 이미 유럽연합 및 영국에서 품목허가를 받았으며, 2025년 6월부터 독일과 영국에서 습성 황반변성 치료용 베바시주맙의 최초 허가된 안과용 제형으로 상업적으로 공급되고 있습니다.
Outlook Therapeutics (NASDAQ: OTLK) a annoncé que la FDA a émis une Complete Response Letter (CRL) concernant ONS-5010/LYTENAVA™ (bevacizumab-vikg), son candidat pour la DMLA humide. La FDA ne peut pas approuver la demande sous sa forme actuelle en raison du manque de preuves substantielles d'efficacité.
La CRL précise que, si l'essai NORSE TWO a atteint son critère principal, l'essai NORSE EIGHT ne l'a pas fait, conduisant la FDA à demander des preuves supplémentaires confirmant l'efficacité. Malgré ce revers aux États-Unis, LYTENAVA™ a déjà obtenu la autorisation de mise sur le marché dans l'Union européenne et au Royaume-Uni et est commercialisée en Allemagne et au Royaume-Uni depuis juin 2025 comme la première formulation ophtalmique autorisée de bevacizumab pour le traitement de la DMLA humide.
Outlook Therapeutics (NASDAQ: OTLK) gab bekannt, dass die FDA ein Complete Response Letter (CRL) für ONS-5010/LYTENAVA™ (bevacizumab-vikg), ihren Wirkstoffkandidaten gegen feuchte AMD, ausgestellt hat. Die FDA kann den Antrag in der derzeitigen Form aufgrund des Mangels an substanziellen Wirksamkeitsnachweisen nicht genehmigen.
Das CRL hebt hervor, dass zwar die NORSE TWO-Studie ihren primären Endpunkt erreicht hat, die NORSE EIGHT-Studie diesen jedoch verfehlt hat, weshalb die FDA zusätzliche bestätigende Wirksamkeitsdaten empfiehlt. Trotz dieses Rückschlags in den USA hat LYTENAVA™ bereits die Marktzulassung in der Europäischen Union und im Vereinigten Königreich erhalten und ist seit Juni 2025 in Deutschland und Großbritannien kommerziell erhältlich – als die erste zugelassene ophthalmische Darreichungsform von Bevacizumab zur Behandlung der feuchten AMD.
- Marketing Authorization already granted in EU and UK markets
- Commercial availability established in Germany and UK since June 2025
- NORSE TWO trial successfully met its primary endpoint
- First authorized ophthalmic formulation of bevacizumab for wet AMD in EU and UK
- FDA rejected the BLA due to lack of substantial evidence of effectiveness
- NORSE EIGHT trial failed to meet primary efficacy endpoint
- Additional confirmatory efficacy evidence required for U.S. approval
- Significant delay expected in U.S. market entry
Insights
FDA rejection of Outlook's wet AMD treatment is a significant setback that likely requires additional clinical trials before potential approval.
The FDA's Complete Response Letter (CRL) for Outlook Therapeutics' ONS-5010 (bevacizumab-vikg) represents a significant regulatory setback for the company. The rejection hinges on a lack of substantial evidence of effectiveness, specifically citing the failure of the NORSE EIGHT study to meet its primary endpoint. While the FDA acknowledged that the earlier NORSE TWO trial did meet its efficacy endpoint, the agency is requesting confirmatory evidence before considering approval.
This regulatory outcome presents a substantial challenge for Outlook Therapeutics. Generating additional confirmatory efficacy data typically requires conducting new clinical trials, which would involve significant time (likely 1-2+ years) and capital investment. For a smaller biopharmaceutical company like Outlook, this represents both a financial and strategic hurdle.
The company does have some positive developments to balance this setback. Outlook has secured Marketing Authorization for LYTENAVA™ (bevacizumab gamma) in both the European Union and United Kingdom, with commercial availability already established in Germany and the UK. This European commercialization provides a potential revenue stream while the company addresses the FDA's concerns.
For context, ONS-5010 is positioned as the first purpose-formulated bevacizumab for intravitreal use in wet AMD, aiming to provide a regulated alternative to compounded Avastin. While the regulatory pathway in the US remains challenging, the company's European authorization strengthens its overall market position and potentially provides financial resources to pursue additional clinical development required by the FDA.
- FDA issues Complete Response Letter (CRL) for resubmitted ONS-5010 BLA
- Outlook Therapeutics plans to work with FDA to address the Agency’s issues
- Company to host a conference call and webcast today, August 28th at 8:30 AM ET
ISELIN, N.J., Aug. 28, 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 its 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).
The CRL included only one deficiency, for a lack of substantial evidence of effectiveness. In the CRL, the FDA advised that, because ONS-5010 did not meet the primary efficacy endpoint in NORSE EIGHT, it is recommended that confirmatory evidence of efficacy be submitted to support the application for ONS-5010. Additionally, the FDA reiterated that NORSE TWO met its primary endpoint for effectiveness.
“While we are very disappointed with this outcome, we intend to meet with the FDA to receive additional clarity on their requirements to potentially approve the first on-label bevacizumab product specifically formulated, manufactured, and packaged for intravitreal use in the United States. We remain committed to providing patients with a safe and effective alternative to compounded Avastin manufactured in the United States,” commented Bob Jahr, Chief Executive Officer of Outlook Therapeutics. “It is important to also note that the CRL identified no other outstanding deficiencies in our BLA.”
In addition to requesting a meeting with the FDA to explore pathways for potential approval in the U.S., Outlook Therapeutics intends to continue its efforts to expand into additional markets in Europe. 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. 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.
Investor Conference Call and Webcast
Outlook Therapeutics management will host a corporate update conference call and webcast today, August 28, 2025 at 8:30 AM ET.
Interested participants and investors may access the conference call by dialing (877) 407-8291 (domestic) or (201) 689-8345 (international). The live webcast will be accessible on the Events page of the Investors section of the Outlook Therapeutics website, outlooktherapeutics.com, and will be archived there for 90 days.
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 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,” “intend,” “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 to meet with the FDA and to work to address the deficiency identified in the CRL, the potential to obtain FDA approval for ONS-5020, plans to expand the commercial availability of LYTENAVA in other markets in Europe, the potential of ONS-5010/LYTENAVA™ as a treatment for wet AMD and to mitigate certain risks associated with the current off-label use of repackaged bevacizumab, 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, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals, including the risk that the Outlook Therapeutics is unable to address the issues identified in the CRL and ultimately obtain FDA approval, 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, 2024, filed with the SEC on December 27, 2024, as supplemented by the Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2025 and 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
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