Outlook Therapeutics® Re-Submits Biologics License Application for ONS-5010 as a Treatment for Wet AMD to the U.S. Food and Drug Administration
Outlook Therapeutics (OTLK) has re-submitted its Biologics License Application (BLA) to the FDA for ONS-5010, branded as LYTENAVA™ (bevacizumab-vikg), for treating wet age-related macular degeneration (wet AMD). The resubmission follows the company's recent regulatory approvals in the EU and UK.
The BLA includes data from the NORSE EIGHT trial, a randomized study of 400 wet AMD patients comparing ONS-5010 to ranibizumab. While ONS-5010 showed clinical improvements with 3.3 to 5.5 letter improvement in vision across timepoints, it did not meet the pre-specified non-inferiority endpoint at week 8. However, anatomical response was comparable between treatments, with ONS-5010 achieving a -123.9 micron reduction in central retinal thickness versus -127.3 microns for ranibizumab.
An FDA decision is expected within six months.
Outlook Therapeutics (OTLK) ha ripresentato la sua Domanda di Licenza Biologica (BLA) alla FDA per ONS-5010, commercializzato come LYTENAVA™ (bevacizumab-vikg), per il trattamento della degenerazione maculare senile umida (wet AMD). La nuova presentazione segue le recenti approvazioni normative dell'azienda nell'UE e nel Regno Unito.
La BLA include dati dal trial NORSE EIGHT, uno studio randomizzato su 400 pazienti con wet AMD che confronta ONS-5010 con ranibizumab. Sebbene ONS-5010 abbia mostrato miglioramenti clinici con un miglioramento della visione da 3.3 a 5.5 lettere nel tempo, non ha raggiunto il punto di non inferiorità predefinito alla settimana 8. Tuttavia, la risposta anatomica è stata comparabile tra i trattamenti, con ONS-5010 che ha ottenuto una riduzione di -123.9 micron nello spessore retinico centrale rispetto a -127.3 micron per ranibizumab.
Una decisione della FDA è attesa entro sei mesi.
Outlook Therapeutics (OTLK) ha vuelto a presentar su Solicitud de Licencia Biológica (BLA) a la FDA para ONS-5010, comercializado como LYTENAVA™ (bevacizumab-vikg), para el tratamiento de la degeneración macular relacionada con la edad húmeda (wet AMD). La nueva presentación sigue a las recientes aprobaciones regulatorias de la empresa en la UE y el Reino Unido.
La BLA incluye datos del ensayo NORSE EIGHT, un estudio aleatorizado de 400 pacientes con wet AMD que compara ONS-5010 con ranibizumab. Aunque ONS-5010 mostró mejoras clínicas con un aumento de visión de 3.3 a 5.5 letras a lo largo del tiempo, no cumplió con el punto de no inferioridad predefinido en la semana 8. Sin embargo, la respuesta anatómica fue comparable entre los tratamientos, con ONS-5010 logrando una reducción de -123.9 micrones en el grosor retiniano central frente a -127.3 micrones para ranibizumab.
Se espera una decisión de la FDA en un plazo de seis meses.
Outlook Therapeutics (OTLK)는 습성 노인성 황반변성(wet AMD) 치료를 위한 ONS-5010(브랜드명: LYTENAVA™)에 대한 생물학적 제품 면허 신청(BLA)을 FDA에 재제출했습니다. 이번 재제출은 유럽연합(EU) 및 영국에서의 최근 규제 승인에 따른 것입니다.
BLA에는 ONS-5010과 라니비주맙을 비교한 400명의 습성 AMD 환자를 대상으로 한 무작위 연구인 NORSE EIGHT 시험의 데이터가 포함되어 있습니다. ONS-5010은 시간에 따라 3.3에서 5.5 글자의 시력 개선을 보였지만, 8주 차에 사전 정의된 비열등성 기준을 충족하지 못했습니다. 그러나 해부학적 반응은 두 치료법 간에 유사했으며, ONS-5010은 중심 망막 두께를 -123.9 마이크론 줄인 반면, 라니비주맙은 -127.3 마이크론 줄였습니다.
FDA의 결정은 6개월 이내에 예상됩니다.
Outlook Therapeutics (OTLK) a soumis à nouveau sa Demande de Licence Biologique (BLA) à la FDA pour ONS-5010, commercialisé sous le nom de LYTENAVA™ (bevacizumab-vikg), pour le traitement de la dégénérescence maculaire liée à l'âge humide (wet AMD). Cette nouvelle soumission fait suite aux récentes approbations réglementaires de l'entreprise dans l'UE et au Royaume-Uni.
La BLA comprend des données de l'
Une décision de la FDA est attendue dans un délai de six mois.
Outlook Therapeutics (OTLK) hat seinen Antrag auf Biologisches Lizenzverfahren (BLA) bei der FDA für ONS-5010, das unter dem Markennamen LYTENAVA™ (bevacizumab-vikg) läuft, zur Behandlung der feuchten altersbedingten Makuladegeneration (feuchte AMD) erneut eingereicht. Die erneute Einreichung folgt den jüngsten behördlichen Genehmigungen des Unternehmens in der EU und im Vereinigten Königreich.
Die BLA umfasst Daten aus der NORSE EIGHT-Studie, einer randomisierten Studie mit 400 Patienten mit feuchter AMD, die ONS-5010 mit Ranibizumab vergleicht. Während ONS-5010 klinische Verbesserungen mit einer Verbesserung der Sehschärfe von 3,3 bis 5,5 Buchstaben über die Zeit zeigte, erreichte es nicht den vorab festgelegten Nichtunterlegenheitsendpunkt in Woche 8. Die anatomische Reaktion war jedoch zwischen den Behandlungen vergleichbar, wobei ONS-5010 eine Reduktion der zentralen Netzhautdicke um -123,9 Mikrometer im Vergleich zu -127,3 Mikrometern für Ranibizumab erzielte.
Eine Entscheidung der FDA wird innerhalb von sechs Monaten erwartet.
- Recent regulatory approvals secured in EU and UK markets
- Comparable anatomical response to existing treatment (ONS-5010: -123.9μm vs ranibizumab: -127.3μm)
- Clinical improvements shown with 3.3 to 5.5 letter vision improvement
- Failed to meet primary non-inferiority endpoint at week 8
- Lower efficacy vs ranibizumab (3.3-5.5 vs 4.5-6.5 letter improvement)
Insights
Outlook Therapeutics' BLA resubmission for ONS-5010 represents a critical regulatory milestone following their previous Complete Response Letter from the FDA. This second attempt includes data from the NORSE EIGHT trial comparing ONS-5010 to ranibizumab in wet AMD patients.
The resubmission carries mixed clinical evidence. While ONS-5010 failed to meet its pre-specified non-inferiority endpoint at week 8, the complete 12-week analysis showed meaningful clinical improvements with BCVA improvements of 3.3-5.5 letters versus 4.5-6.5 letters for ranibizumab. Importantly, the anatomical response (central retinal thickness reduction) was nearly identical between treatments at -123.9 vs -127.3 microns.
The FDA's decision, expected within six months, is pivotal for OTLK's
Success hinges on whether regulators will accept the anatomical efficacy and overall clinical profile despite missing the primary endpoint. Any approval decision would transform this small-cap company's commercial prospects in the substantial wet AMD market.
The NORSE EIGHT data presents an interesting clinical picture that regulators will need to carefully evaluate. While ONS-5010 missed its primary endpoint for visual acuity improvement at 8 weeks, the nearly identical anatomical response between bevacizumab-vikg and ranibizumab (-123.9 vs -127.3 microns in central retinal thickness) is clinically significant. This parameter is particularly important as retinal specialists heavily weigh anatomical improvements when assessing treatment efficacy.
The bevacizumab molecule has long been used off-label for wet AMD through hospital pharmacy repackaging, but this practice introduces variability and potential sterility concerns. An FDA-approved ophthalmic formulation would address these safety issues while potentially reducing treatment costs compared to other approved anti-VEGF agents.
The visual acuity improvements, while numerically lower than ranibizumab (3.3-5.5 vs 4.5-6.5 letters), still demonstrate clinical benefit. The slight difference may be acceptable to clinicians given the well-established efficacy profile of bevacizumab in ophthalmology and its potential cost advantages.
The FDA will likely weigh the totality of evidence, including consistent anatomical improvements, progressive visual benefits over 12 weeks, and the public health need for an approved ophthalmic bevacizumab option. Their decision will significantly impact treatment paradigms for the millions of patients with this sight-threatening condition.
ISELIN, N.J., Feb. 28, 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 it has re-submitted its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ONS-5010, an investigational ophthalmic product which, if approved, will be branded as LYTENAVA™ (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).
“We remain committed to bringing an ophthalmic bevacizumab to market in the United States and providing retina patients suffering from wet AMD with a much needed treatment option that has the potential to address the problems associated with unapproved repackaged bevacizumab. Our team has worked diligently to address the FDA’s requests and we believe this resubmission provides the necessary evidence to support approval of the ONS-5010 BLA in the United States,” commented Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics. “This resubmission marks a very significant milestone and puts us another step closer to a transformed Outlook Therapeutics.”
The ONS-5010 BLA resubmission is based on the efficacy and safety demonstrated in NORSE EIGHT, as well as additional chemistry, manufacturing and controls (CMC) information requested by the FDA. As previously announced, following Type A meetings with the FDA in Q4 CY2023 to address the ONS-5010 Complete Response Letter (CRL), the FDA informed Outlook Therapeutics that, in order to meet the FDA’s requirement for a second adequate and well-controlled clinical trial of ONS-5010, it could conduct a 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 (NORSE EIGHT). Outlook Therapeutics believes that the complete data set for NORSE EIGHT and the additional CMC information in the BLA resubmission, 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. A decision from the FDA is expected within six months.
NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 / LYTENAVA™ or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint is the mean change in best corrected visual acuity (BCVA) from baseline to week 8. In November 2024, Outlook Therapeutics reported that in NORSE EIGHT, ONS-5010 demonstrated a mean 4.2 letter improvement in best corrected visual acuity (BCVA), which did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the FDA.
In January 2025, Outlook Therapeutics announced results from the completed analysis of the 12-week safety and efficacy results for NORSE EIGHT, which indicated that ONS-5010 demonstrated clinically meaningful anatomic and functional improvements at each study timepoint. BCVA data across all study timepoints demonstrated an improvement in vision, increasing over time, and the presence of biologic activity. Results from the 12-week analysis demonstrated a mean improvement in BCVA of 3.3 to 5.5 letters in the ONS-5010 arm across the 4, 8, and 12 week timepoints measured in the study, compared to a mean 4.5 to 6.5 letter improvement in the ranibizumab arm over the same timepoints. Additionally, the complete NORSE EIGHT data set showed that 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, virtually no difference between the arms. Central retinal thickness is a key indicator of effectiveness used by retina specialists in the treatment of wet AMD.
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 second quarter of calendar 2025. In the United States, ONS-5010/LYTENAVA™ is investigational, and a BLA has been resubmitted 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’ ability to remediate or otherwise resolve deficiencies identified in the CRL issued by the FDA in the resubmitted BLA, expectations concerning decisions of regulatory bodies and the timing thereof, expectations concerning the therapeutic potential of LYTENAVA™ as a treatment of wet AMD, 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, Outlook Therapeutics’ plans for commercial launch of LYTENAVA™ in the UK and EU and timing thereof, Outlook Therapeutics’ commercialization strategy, 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
When will the FDA decide on Outlook Therapeutics' ONS-5010 BLA resubmission?
What were the key results of OTLK's NORSE EIGHT trial for ONS-5010?
How does ONS-5010's efficacy compare to ranibizumab in wet AMD treatment?
Which regulatory approvals has OTLK already secured for ONS-5010?
