Outlook Therapeutics® Announces Completion of Enrollment in NORSE EIGHT Clinical Trial

Rhea-AI Summary

Outlook Therapeutics (Nasdaq: OTLK) has announced the completion of enrollment for its NORSE EIGHT clinical trial, evaluating ONS-5010 in wet AMD patients. This trial, subject to a Special Protocol Assessment (SPA) agreement with the FDA, is the final anticipated clinical study before the expected resubmission of the company's Biologics License Application (BLA) for ONS-5010.

Key points:

• NORSE EIGHT is a randomized, controlled study comparing ONS-5010 to ranibizumab
• Topline results are expected in Q4 2024
• BLA resubmission is planned for Q1 2025
• The trial aims to address the clinical deficiency identified in the previous Complete Response Letter

If approved by the FDA, Outlook Therapeutics plans to commercialize ONS-5010/LYTENAVA™ (bevacizumab-vikg) directly in the U.S. and is exploring partnering options for Europe and other regions.

Positive

• Completed enrollment for NORSE EIGHT clinical trial, the final anticipated study before BLA resubmission
• Received FDA agreement on NORSE EIGHT trial protocol under Special Protocol Assessment (SPA)
• On track to report topline results in Q4 2024 and resubmit BLA in Q1 2025
• Already achieved regulatory approval in the European Union and UK for ONS-5010 in wet AMD treatment

Negative

• Previous BLA submission received a Complete Response Letter (CRL) from FDA, requiring additional clinical trial
• Commercialization plans dependent on FDA approval, which is not guaranteed

Medical Research Analyst

The completion of enrollment for the NORSE EIGHT trial is a significant milestone for Outlook Therapeutics. This study, designed under a Special Protocol Assessment (SPA) agreement with the FDA, aims to address the clinical deficiency identified in the previous Complete Response Letter. The trial's design as a non-inferiority study comparing ONS-5010 to ranibizumab is strategically sound, potentially paving the way for FDA approval.

The rapid enrollment - completing in less than 8 months - suggests strong interest from both patients and clinicians, which could bode well for future market adoption if approved. The planned topline results in Q4 2024 and BLA resubmission in Q1 2025 provide a clear timeline for investors to monitor. However, it's important to note that while positive results could lead to approval, there's always inherent risk in clinical trials, especially given the previous CRL.

Financial Analyst

Outlook Therapeutics' progress with ONS-5010 could have significant financial implications. The European and UK approvals earlier this year provide a foundation for potential revenue streams. If FDA approval follows, it could open up the lucrative U.S. market for wet AMD treatment.

The company's plan to commercialize directly in the U.S. while exploring partnerships for other regions suggests a balanced approach to maximize revenue potential. However, investors should consider the costs associated with commercialization and potential competition in the market. The timeline for potential approval and launch allows for financial planning, but also means continued cash burn until then. The stock's performance may be volatile as it approaches key milestones, particularly the topline results announcement.

Market Research Analyst

The wet AMD market is substantial and growing, making ONS-5010 a potentially valuable asset if approved. Outlook Therapeutics' focus on an ophthalmic formulation of bevacizumab could fill a significant market gap, offering a potentially more cost-effective alternative to current treatments.

The company's strategy to address both clinical and CMC issues from the previous CRL demonstrates a comprehensive approach to gaining approval. Market reception could be positive given the unmet need for authorized bevacizumab formulations in ophthalmology. However, the success will ultimately depend on the NORSE EIGHT results and the ability to differentiate from existing treatments. Investors should monitor not only the efficacy data but also any safety signals that could impact market adoption.

• Topline results from NORSE EIGHT expected in Q4 CY2024

ISELIN, N.J., Sept. 04, 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 the completion of enrollment for its NORSE EIGHT clinical trial evaluating ONS-5010 in wet AMD patients. NORSE EIGHT is the subject of a Special Protocol Assessment (SPA) agreement with the FDA, and, if successful, is the final anticipated clinical trial required before expected resubmission of the Outlook Therapeutics’ Biologics License Application (BLA) for ONS-5010.

NORSE EIGHT is 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 will receive injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint is mean change in best corrected visual acuity (BCVA) from baseline to week 8. Outlook Therapeutics remains on track to report NORSE EIGHT topline results in Q4 CY2024. The resubmission of the ONS-5010 BLA is planned for Q1 CY2025.

“We are very pleased to complete this important milestone in our effort to resubmit our BLA for ONS-5010. On behalf of Outlook Therapeutics, I would like to express gratitude to the patients and dedicated teams at the clinical sites, as well as our clinical and regulatory staff, who enrolled this entire patient population in less than 8 months after our SPA agreement from FDA,” commented Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics. “We remain confident in the potential of ONS-5010, if approved, to meet the needs of retina specialists, patients, and payers. With enrollment now complete, we plan to report topline efficacy results in the fourth calendar quarter of this year.”

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 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) to support the resubmission of the ONS-5010 BLA. In January 2024, Outlook Therapeutics received written agreement on the NORSE EIGHT trial protocol and statistical analysis plan from the FDA under the SPA. The SPA also confirms in writing that if the NORSE EIGHT trial is successful, it would satisfy the FDA’s requirement for a second adequate and well-controlled clinical trial to fully address the clinical deficiency identified in the CRL. In addition, Outlook Therapeutics has completed Type C and Type D meetings with the FDA to address the open chemical, manufacturing and control (CMC) items in the CRL and expects to resolve these comments prior to the expected completion of NORSE EIGHT.

If approved by the FDA, Outlook Therapeutics plans to commercialize ONS-5010/LYTENAVA™ (bevacizumab-vikg) directly in the U.S. and is also assessing partnering options for LYTENAVA™ (bevacizumab gamma) in Europe and other regions outside of the U.S.

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 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,” “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 potential as the first and only European Commission, MHRA or FDA-approved ophthalmic formulation of bevacizumab for use in treating retinal diseases in the EU, UK, and United States, the timing for completion of NORSE EIGHT and resubmission of the BLA for ONS-5010, 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, 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 (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 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: 833.475.8247
OTLK@jtcir.com

FAQ

What is the purpose of Outlook Therapeutics' NORSE EIGHT clinical trial for OTLK stock?

The NORSE EIGHT clinical trial is evaluating ONS-5010 in wet AMD patients. It's the final anticipated study required before resubmitting the Biologics License Application (BLA) to the FDA for ONS-5010, addressing previous clinical deficiencies.

When are the topline results for OTLK's NORSE EIGHT trial expected?

Outlook Therapeutics expects to report topline results from the NORSE EIGHT trial in the fourth quarter of 2024.

What is the primary endpoint of the NORSE EIGHT trial for OTLK's ONS-5010?

The primary endpoint of the NORSE EIGHT trial is the mean change in best corrected visual acuity (BCVA) from baseline to week 8.

When does Outlook Therapeutics (OTLK) plan to resubmit its BLA for ONS-5010?

Outlook Therapeutics plans to resubmit its Biologics License Application (BLA) for ONS-5010 in the first quarter of 2025, following the completion of the NORSE EIGHT trial.