Outlook Therapeutics® Announces Presentation of Efficacy and Safety Results from NORSE EIGHT Clinical Trial Evaluating ONS-5010 for the Treatment of Wet AMD
Outlook Therapeutics (OTLK) presented data from its NORSE EIGHT clinical trial evaluating ONS-5010 for wet AMD treatment at the Hawaiian Eye and Retina 2025 Meeting. The trial compared ONS-5010 with ranibizumab in newly diagnosed wet AMD patients.
Key results showed ONS-5010 achieved mean BCVA improvements of +3.3, +4.2, and +5.5 letters at Months 1, 2, and 3 respectively. The treatment demonstrated non-inferiority to Lucentis at 4 and 12 weeks, though it didn't meet the pre-specified non-inferiority endpoint at week 8. Anatomical response showed similar results between treatments, with central retinal thickness reduction of -123.9 microns for ONS-5010 versus -127.3 microns for ranibizumab.
The company plans to resubmit its BLA in Q1 2025. ONS-5010 has already received Marketing Authorization in the EU and UK, with European launch planned for first half of 2025.
Outlook Therapeutics (OTLK) ha presentato i dati del suo studio clinico NORSE EIGHT che valuta ONS-5010 per il trattamento della AMD umida durante il Meeting Hawaiian Eye and Retina 2025. Lo studio ha confrontato ONS-5010 con ranibizumab in pazienti con AMD umida appena diagnosticata.
I risultati chiave hanno mostrato che ONS-5010 ha raggiunto miglioramenti medi della BCVA di +3.3, +4.2 e +5.5 lettere rispettivamente nei Mesi 1, 2 e 3. Il trattamento ha dimostrato non inferiorità rispetto a Lucentis a 4 e 12 settimane, anche se non ha soddisfatto l'obiettivo di non inferiorità predefinito alla settimana 8. La risposta anatomica ha mostrato risultati simili tra i trattamenti, con una riduzione dello spessore retinico centrale di -123.9 micron per ONS-5010 rispetto a -127.3 micron per ranibizumab.
L'azienda prevede di ri-sottoporre la sua BLA nel primo trimestre del 2025. ONS-5010 ha già ricevuto l'Autorizzazione alla Commercializzazione nell'UE e nel Regno Unito, con un lancio europeo previsto per la prima metà del 2025.
Outlook Therapeutics (OTLK) presentó datos de su ensayo clínico NORSE EIGHT que evalúa ONS-5010 para el tratamiento de la AMD húmeda en la Reunión Hawaiian Eye and Retina 2025. El ensayo comparó ONS-5010 con ranibizumab en pacientes recién diagnosticados con AMD húmeda.
Los resultados clave mostraron que ONS-5010 logró mejoras medias en BCVA de +3.3, +4.2 y +5.5 letras en los Meses 1, 2 y 3 respectivamente. El tratamiento demostró no inferioridad frente a Lucentis a las 4 y 12 semanas, aunque no cumplió con el objetivo de no inferioridad preestablecido a la semana 8. La respuesta anatómica mostró resultados similares entre los tratamientos, con una reducción del grosor retiniano central de -123.9 micrones para ONS-5010 frente a -127.3 micrones para ranibizumab.
La compañía planea volver a presentar su BLA en el primer trimestre de 2025. ONS-5010 ya ha recibido la Autorización de Comercialización en la UE y el Reino Unido, con un lanzamiento europeo previsto para la primera mitad de 2025.
Outlook Therapeutics (OTLK)가 하와이안 아이와 망막 2025 회의에서 습성 AMD 치료를 위한 ONS-5010에 대한 NORSE EIGHT 임상 시험 데이터를 발표하였습니다. 이 시험은 Newly diagnosed 습성 AMD 환자에서 ONS-5010과 라니비주맙을 비교했습니다.
주요 결과에 따르면 ONS-5010은 각각 1, 2, 3개월에 +3.3, +4.2, +5.5 글자의 평균 BCVA 개선을 달성했습니다. 이 치료는 4주와 12주에 Lucentis에 비해 비열등성을 보여주었으나, 8주 차에 사전 규정된 비열등성 기준을 충족하지는 못했습니다. 해부학적 반응은 두 치료 간에 유사한 결과를 보여주었고, ONS-5010은 -123.9 마이크론, 라니비주맙은 -127.3 마이크론의 중심 망막 두께 감소를 기록했습니다.
회사는 2025년 1분기에 BLA를 다시 제출할 계획입니다. ONS-5010은 이미 EU와 UK에서 판매 허가를 받았으며 2025년 상반기에 유럽 출시를 계획하고 있습니다.
Outlook Therapeutics (OTLK) a présenté des données de son essai clinique NORSE EIGHT évaluant ONS-5010 pour le traitement de l'AMD humide lors de la réunion Hawaiian Eye and Retina 2025. L'essai a comparé ONS-5010 avec le ranibizumab chez des patients récemment diagnostiqués avec une AMD humide.
Les résultats clés ont montré qu'ONS-5010 a atteint des améliorations moyennes de la BCVA de +3.3, +4.2 et +5.5 lettres aux mois 1, 2 et 3 respectivement. Le traitement a démontré une non-infériorité par rapport à Lucentis à 4 et 12 semaines, bien qu'il n'ait pas atteint le critère de non-infériorité prédéfini à la semaine 8. La réponse anatomique a montré des résultats similaires entre les traitements, avec une réduction de l'épaisseur rétinienne centrale de -123.9 microns pour ONS-5010 contre -127.3 microns pour le ranibizumab.
L'entreprise prévoit de redéposer sa BLA au premier trimestre de 2025. ONS-5010 a déjà reçu une autorisation de mise sur le marché dans l'UE et au Royaume-Uni, avec un lancement européen prévu pour la première moitié de 2025.
Outlook Therapeutics (OTLK) hat Daten aus seiner NORSE EIGHT-Studie präsentiert, die ONS-5010 zur Behandlung von feuchter AMD bewertet, während des Hawaiian Eye and Retina 2025 Meetings. Die Studie verglich ONS-5010 mit Ranibizumab bei neu diagnostizierten Patienten mit feuchter AMD.
Wichtige Ergebnisse zeigten, dass ONS-5010 mittlere BCVA-Verbesserungen von +3.3, +4.2 und +5.5 Buchstaben in den Monaten 1, 2 und 3 erreichte. Die Behandlung zeigte bei 4 und 12 Wochen eine Nichtunterlegenheit gegenüber Lucentis, erreichte jedoch das vorgegebene Nichtunterlegenheitsziel in Woche 8 nicht. Die anatomische Reaktion zeigte ähnliche Ergebnisse zwischen den Behandlungen, mit einer Reduktion der zentralen Netzhautdicke von -123.9 Mikrometern für ONS-5010 im Vergleich zu -127.3 Mikrometern für Ranibizumab.
Das Unternehmen plant, seine BLA erneut einzureichen im ersten Quartal 2025. ONS-5010 hat bereits eine Marktzulassung in der EU und Großbritannien erhalten, mit einer europäischen Markteinführung, die für die erste Hälfte von 2025 vorgesehen ist.
- Achieved Marketing Authorization in EU and UK for wet AMD treatment
- Demonstrated non-inferiority to Lucentis at 4 and 12 weeks
- Showed consistent safety profile across all NORSE clinical trials
- European launch planned for first half of 2025
- Failed to meet pre-specified non-inferiority endpoint at week 8
- Reported adverse events including conjunctival hemorrhage in 2.5% of participants
Insights
The NORSE EIGHT clinical trial results present a complex picture for Outlook Therapeutics' ONS-5010. The data reveals several critical insights that warrant careful analysis:
The efficacy profile shows progressive improvement over time:
- Month 1: +3.3 letters improvement
- Month 2: +4.2 letters improvement
- Month 3: +5.5 letters improvement
While missing the week 8 primary endpoint is concerning, the demonstration of non-inferiority at Month 3 (p=0.0043) provides a compelling argument for FDA consideration. The anatomical response data, showing comparable central retinal thickness reduction (-123.9 vs -127.3 microns), supports the drug's therapeutic effectiveness.
The safety profile is particularly encouraging, with no cases of retinal vasculitis and minimal adverse events to conjunctival hemorrhage in
The strategic positioning is notable: ONS-5010 has already secured EU and UK approval as LYTENAVA™, with planned European launch in H1 2025. This creates a unique market opportunity as the first authorized ophthalmic bevacizumab formulation, addressing the limitations of current off-label repackaged options.
For investors, three key factors merit attention:
- The planned Q1 2025 BLA resubmission timeline remains on track, suggesting management confidence in the comprehensive data package
- The established EU/UK regulatory success provides validation and potential revenue streams independent of FDA decision
- The safety and efficacy profile, while not superior to ranibizumab, demonstrates sufficient comparability to support market adoption
- Data presented at Hawaiian Eye and Retina 2025 Meeting
- Results confirmed that intravitreal ONS-5010 provided early and sustained anatomic improvements, with steady gains in BCVA and reliable, consistent safety
- ONS-5010 demonstrated to be non-inferior to Lucentis at 4 and 12 weeks
- Company on track for anticipated BLA resubmission in calendar Q1 2025
ISELIN, N.J., Jan. 23, 2025 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union (EU) and the United Kingdom (UK) for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), today announced the presentation of data from NORSE EIGHT at the Hawaiian Eye and Retina 2025 Meeting being held January 18-24, 2025 in Kauai, HI.
As part of the meeting, Baruch D. Kuppermann, MD, PhD, of Gavin Herbert Eye Institute, University of California, Irvine, CA presented the abstract titled, “ONS-5010 (bevacizumab-vikg) versus Ranibizumab for Neovascular Age-related Macular Degeneration: Results from the NORSE-EIGHT Noninferiority Randomized Trial,” highlighting the Company’s recently announced 12-week safety and efficacy results for the NORSE EIGHT clinical trial evaluating ONS-5010 in wet AMD patients.
The NORSE EIGHT clinical trial 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, and returned for a final study visit at week 12. The primary endpoint was mean change in BCVA from baseline to week 8.
“The NORSE EIGHT results provide additional evidence to the retina community that ONS-5010 meets the expectations for an ophthalmic formulation of bevacizumab, without the challenges that can arise from using repackaged, off-label formulations available today. The reductions in central retinal thickness observed in the trial confirmed that ONS-5010 reduced fluid in the retina on par with ranibizumab, and I’ve been encouraged with the consistency of this treatment across all NORSE clinical studies,” said Dr. Kuppermann.
Key Highlights
- Mean BCVA at baseline was 58.8 ETDRS letters for the ONS-5010 group and 59.9 letters for the ranibizumab group.
- ONS-5010 demonstrated mean BCVA improvements of +3.3, +4.2 and +5.5 letters at Months 1, 2, and 3 respectively.
- The difference in mean BCVA between ONS-5010 and ranibizumab was -1.009 letters (
95% confidence interval, -2.865, 0.848), meeting the noninferiority margin at Month 3 (p=0.0043) (applying the statistical parameters from the week 8 primary endpoint with the lower bound of the non-inferiority margin at -3.5 with a95% confidence interval). - As previously announced, 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 with the U.S. Food and Drug Administration (FDA).
- Anatomical response was similar between treatments, with a reduction in central retinal thickness of -123.9 microns for ONS-5010 treated eyes and -127.3 microns for the ranibizumab group.
- ONS-5010 was generally well-tolerated with overall ocular adverse event rates comparable to ranibizumab, with no cases of retinal vasculitis reported in either study arm. The most commonly reported adverse event (AE) was conjunctival hemorrhage, which occurred in 5 (
2.5% ) participants in each group. - Safety results demonstrated across the full duration of NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials.
“Based on the data seen to date, we continue to be encouraged by the potential of ONS-5010 for the treatment of wet AMD. We believe that the complete data set from all of our NORSE clinical trials supports the resubmission of our BLA in the United States for the treatment of wet AMD, which we remain on track to complete this quarter,” added Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics.
Based on the completed analysis of the 12-week results, Outlook Therapeutics plans to resubmit the Biologics License Application (BLA) application for ONS-5010 in the first quarter of calendar 2025.
For more information about the NORSE EIGHT study, visit clinicaltrials.gov and reference identifier NCT06190093.
In the EU and the UK, ONS-5010/LYTENAVA™ (bevacizumab gamma) has already been granted Marketing Authorization. Outlook Therapeutics intends to continue efforts to begin launching in Europe in the first half of calendar 2025.
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 AMD.
In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational.
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 if successful, 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,” “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, Outlook Therapeutics’ plans for commercial launch of LYTENAVA™ in the UK and EU and timing thereof, as well as the potential to launch with a partner, expectations concerning the therapeutic potential of LYTENAVA™ as a treatment of wet AMD, Outlook Therapeutics’ ability to remediate or otherwise resolve deficiencies identified in the CRL issued by the FDA, plans to resubmit the BLA for ONS-5010 and the timing thereof, Outlook Therapeutics’ commercialization strategy, expectations concerning decisions of regulatory bodies and the timing thereof, ONS-5010/LYTENAVA™’s potential as the first FDA-approved ophthalmic formulation of bevacizumab for use in treating retinal indications, including wet AMD, in the United States 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, 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 (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, and future quarterly 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
FAQ
What were the key efficacy results of OTLK's NORSE EIGHT trial for ONS-5010?
When will Outlook Therapeutics (OTLK) resubmit its BLA for ONS-5010?
What were the safety results of ONS-5010 in the NORSE EIGHT trial?
When does OTLK plan to launch ONS-5010 in Europe?
