Outlook Therapeutics® Announces Preliminary Topline Results of NORSE EIGHT Clinical Trial
Outlook Therapeutics announced preliminary topline results of NORSE EIGHT trial for ONS-5010 in wet AMD patients. The trial did not meet its pre-specified non-inferiority endpoint at week 8 compared to ranibizumab. The ONS-5010 arm showed +4.2 letter improvement in BCVA versus +6.3 letters for ranibizumab. Despite not meeting the endpoint, the drug demonstrated vision improvement, biologic activity, and favorable safety profile. Final efficacy data is expected in January 2025, with BLA resubmission planned for Q1 2025. The company maintains European and UK marketing authorization for LYTENAVA™, with potential launch in these markets in 2025.
Outlook Therapeutics ha annunciato i risultati preliminari della fase clinica NORSE EIGHT per ONS-5010 nei pazienti con AMD umida. Lo studio non ha raggiunto il suo obiettivo prestabilito di non inferiorità alla settimana 8 rispetto al ranibizumab. Il braccio ONS-5010 ha mostrato un miglioramento di +4,2 lettere nella BCVA rispetto a +6,3 lettere per il ranibizumab. Nonostante il mancato raggiungimento dell'obiettivo, il farmaco ha dimostrato un miglioramento della visione, attività biologica e un profilo di sicurezza favorevole. I dati finali di efficacia sono attesi per gennaio 2025, con una nuova presentazione della BLA pianificata per il primo trimestre del 2025. L'azienda mantiene l'autorizzazione al commercio in Europa e nel Regno Unito per LYTENAVA™, con un possibile lancio in questi mercati nel 2025.
Outlook Therapeutics anunció los resultados preliminares del ensayo NORSE EIGHT para ONS-5010 en pacientes con AMD húmeda. El ensayo no alcanzó su objetivo de no inferioridad especificado para la semana 8 en comparación con el ranibizumab. El grupo de ONS-5010 mostró una mejora de +4.2 letras en BCVA frente a +6.3 letras para el ranibizumab. A pesar de no cumplir con el objetivo, el fármaco demostró mejoría en la visión, actividad biológica y un perfil de seguridad favorable. Se esperan los datos finales de eficacia en enero de 2025, con una nueva presentación de BLA prevista para el primer trimestre de 2025. La empresa mantiene la autorización de comercialización en Europa y el Reino Unido para LYTENAVA™, con un posible lanzamiento en estos mercados en 2025.
Outlook Therapeutics는 습기 macular degeneration(AMD) 환자에 대한 ONS-5010의 NORSE EIGHT 시험의 초기 주요 결과를 발표했습니다. 이 시험은 주와 8주에서 ranibizumab에 비해 미리 정해진 비열등성 기준을 충족하지 못했습니다. ONS-5010 그룹은 BCVA에서 +4.2자의 개선을 보여주었고, ranibizumab은 +6.3자의 개선을 보여주었습니다. 기준에 도달하지 못했음에도 불구하고, 이 약물은 시력 개선, 생물학적 활성을 보여주었고 유리한 안전성 프로파일을 가지고 있습니다. 최종 효능 데이터는 2025년 1월에 예상되고, BLA의 재신청은 2025년 1분기에 계획되어 있습니다. 이 회사는 LYTENAVA™의 유럽 및 영국 마케팅 승인을 유지하고 있으며, 2025년에 이 시장에서의 출시 가능성이 있습니다.
Outlook Therapeutics a annoncé les résultats préliminaires de l'essai NORSE EIGHT pour ONS-5010 chez les patients atteints de DMLA humide. L'essai n'a pas atteint son objectif de non-infériorité prédéfini à la semaine 8 par rapport au ranibizumab. Le groupe ONS-5010 a montré une amélioration de +4,2 lettres en ACVA contre +6,3 lettres pour le ranibizumab. Malgré le non-atteinte de l'objectif, le médicament a démontré une amélioration de la vision, une activité biologique, et un profil de sécurité favorable. Les données finales d'efficacité sont attendues en janvier 2025, avec une nouvelle soumission de BLA prévue pour le premier trimestre 2025. L'entreprise maintient l'autorisation de mise sur le marché européenne et britannique pour LYTENAVA™, avec un lancement potentiel sur ces marchés en 2025.
Outlook Therapeutics gab die vorläufigen topline Ergebnisse der NORSE EIGHT Studie zu ONS-5010 bei Patienten mit feuchter AMD bekannt. Die Studie erreichte nicht den festgelegten Nicht-Unterlegungsendpunkt in der achten Woche im Vergleich zu Ranibizumab. Die ONS-5010 Gruppe zeigte eine Verbesserung von +4,2 Buchstaben in BCVA im Vergleich zu +6,3 Buchstaben für Ranibizumab. Obwohl der Endpunkt nicht erreicht wurde, zeigte das Medikament eine Verbesserung des Sehens, biologischen Aktivität und ein günstiges Sicherheitsprofil. Die endgültigen Wirksamkeitsdaten werden im Januar 2025 erwartet, mit einer Neuregulierung des BLA, die für das erste Quartal 2025 geplant ist. Das Unternehmen hält die Zulassung für den europäischen und britischen Markt für LYTENAVA™ aufrecht, mit einer möglichen Markteinführung in diesen Märkten im Jahr 2025.
- Maintained favorable safety profile consistent with previous trials
- Already secured marketing authorization in EU and UK
- Demonstrated +4.2 letter improvement in vision (BCVA)
- Completed remediation of CMC comments from previous CRL
- Failed to meet primary non-inferiority endpoint vs ranibizumab
- Lower efficacy compared to ranibizumab (+4.2 vs +6.3 letters)
- BLA resubmission delayed to Q1 2025
- European launch delayed to 2025
Insights
The Phase 3 NORSE EIGHT trial results represent a significant setback for Outlook Therapeutics' ONS-5010. The trial failed to meet its primary endpoint of non-inferiority compared to ranibizumab at week 8, with a
The safety profile remains favorable, consistent with previous NORSE trials, which is a positive aspect. However, the FDA approval pathway now becomes more challenging. The company plans to proceed with BLA resubmission in Q1 2025 after receiving 3-month data, but the failed primary endpoint significantly reduces chances of approval without additional clinical evidence.
The EU/UK approval provides some commercial opportunity, but U.S. market access remains important for the company's success. The competitive landscape in wet AMD treatment continues to favor established options like ranibizumab.
- Final efficacy data expected in January 2025
- Anticipate resubmission of BLA in calendar Q1 2025
ISELIN, N.J., Nov. 27, 2024 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union and the United Kingdom earlier this year for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), today announced preliminary topline results of NORSE EIGHT, the second of two adequate and well controlled clinical trials evaluating ONS-5010 in wet AMD patients. Upon the completion of analysis of the final results of NORSE EIGHT, Outlook Therapeutics plans to resubmit the Biologics License Application (BLA) application for ONS-5010 in the first quarter of calendar 2025.
In the NORSE EIGHT trial, ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the U.S. Food and Drug Administration (FDA). However, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010. Analysis of the data is ongoing as the month 3 data from NORSE EIGHT is being collected, which is expected to be available in January 2025. Upon receipt of the full month 3 efficacy and safety results for NORSE EIGHT, Outlook Therapeutics plans to resubmit the BLA application for ONS-5010 in the first quarter of calendar 2025. In addition, plans for a potential 2025 launch in the UK and Germany are ongoing, where LYTENAVA™ has received European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics remains confident that ONS-5010/ LYTENAVA™ is an important therapy for the treatment of wet AMD in place of off-label repackaged bevacizumab that has not received regulatory approval for use in ophthalmology.
The pre-specified non-inferiority endpoint at week 8 set forth in the SPA with the FDA was measured by mean change in best corrected visual acuity (BCVA) from baseline to week 8. The difference in the means between the ONS-5010 and ranibizumab in the NORSE EIGHT trial was -2.257 BCVA letters with a
| Mean change in BCVA at week 8 | Non-Inferiority | |
| ONS-5010 1.25 mg | +4.2 letters | P-value: 0.0863 |
| Ranibizumab 0.5mg | +6.3 letters |
In NORSE EIGHT, ONS-5010 was generally well-tolerated with overall ocular adverse event rates comparable to ranibizumab. The safety results demonstrated in NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials, with no cases of retinal vasculitis reported in either study arm. Additional safety and efficacy data from the NORSE EIGHT trial will be analyzed after all subjects complete their final visit at month 3.
Remediation of the Chemistry, Manufacturing and Controls (CMC) comments in the Complete Response Letter (CRL) is complete and has been closely aligned with the FDA in type C and type D meetings.
In the European Union and the United Kingdom, ONS-5010/LYTENAVA™ (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics intends to continue efforts to begin launching in Europe in 2025 either directly or with a licensing partner. Discussions with potential licensing partners for markets outside of the United States are ongoing.
About NORSE EIGHT
NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at day 0 (randomization), week 4, and week 8 visits. The primary endpoint was mean change in best corrected visual acuity (BCVA) from baseline to week 8. For more information about the NORSE EIGHT study, visit clinicaltrials.gov and reference identifier NCT06190093.
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 European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet age-related macular degeneration (wet AMD).
In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational and is being evaluated in an ongoing non-inferiority study for the treatment of wet AMD.
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), for the treatment of retina diseases, including wet AMD. 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 is working to initiate its commercial launch of LYTENAVA™ (bevacizumab gamma) in the EU and the UK as a treatment for wet AMD, expected in the first half of calendar 2025. In the United States, ONS-5010/LYTENAVA™ is investigational, is being evaluated in an ongoing non-inferiority study for the treatment of wet AMD, and the data may be sufficient for Outlook to resubmit a BLA to the FDA in the United States. 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,” “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, ONS-5010’s status as the first and only European Commission, MHRA approved ophthalmic formulation of bevacizumab for use in treating retinal diseases in the EU and UK, and plans to continue analyzing data for the NORSE EIGHT trial and the potential to resubmit the BLA for ONS-5010 and the timing thereof, expectations concerning Outlook Therapeutics’ ability to remediate or otherwise resolve deficiencies identified in the CRL issued by the FDA, including with respect to an additional clinical trial and CMC issues, expectations concerning decisions of regulatory bodies and the timing thereof, plans for commercial launch of ONS-5010 in the UK and EU and the timing thereof, including the potential to launch with a partner, expectations concerning the sufficiency of the Company’s cash resources 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 data from the NORSE EIGHT trial does not support the resubmission or subsequent filing by the FDA of the ONS-5010 BLA, 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, 2023, filed with the SEC on December 22, 2023, 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, high interest rates, 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
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