Outlook Therapeutics has reported significant progress in its regulatory pathway for ONS-5010/LYTENAVA™ (bevacizumab-vikg or bevacizumab gamma), positioning the investigational therapy as potentially the first approved ophthalmic formulation of bevacizumab for treating retinal diseases.
European and UK Regulatory Milestones
In a major regulatory advancement, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for ONS-5010/LYTENAVA™ for the treatment of wet age-related macular degeneration (wet AMD). This recommendation supports the grant of marketing authorization by the European Commission, with a decision expected within approximately 67 days of the CHMP opinion.
If approved, the authorization will automatically apply across all 27 EU Member States, with Iceland, Norway, and Liechtenstein following within 30 days. The company anticipates receiving an initial ten years of market exclusivity in the EU for the product.
Building on this momentum, Outlook Therapeutics has also submitted a Marketing Authorization Application (MAA) to the UK's Medicines and Healthcare products Regulatory Agency (MHRA). This submission was completed under the new International Recognition Procedure (IRP), which allows the MHRA to rely on the CHMP's positive opinion.
US Clinical and Regulatory Progress
In the United States, Outlook Therapeutics is advancing the NORSE EIGHT clinical trial following guidance from the FDA. This randomized, controlled, parallel-group study is evaluating ONS-5010 versus ranibizumab in approximately 400 newly diagnosed wet AMD patients. The trial design includes a 3-month treatment period with a primary efficacy endpoint at 2 months, measuring mean change in best corrected visual acuity (BCVA) from baseline to week 8.
Russell Trenary, President and CEO of Outlook Therapeutics, noted, "We are extremely pleased with our corporate, clinical, and regulatory progress. On the regulatory front, we continue to drive toward anticipated marketing authorization of ONS-5010 in the EU and have also submitted our marketing application for authorization in the UK. In the US, we are executing on our NORSE EIGHT clinical trial and advancing toward a topline data readout expected in the fourth quarter of calendar year 2024."
Currently, over 30% of the required subjects have been enrolled in NORSE EIGHT. The company expects to complete enrollment in Q3 2024, with topline results and planned resubmission of the Biologics License Application (BLA) to the FDA by the end of 2024.
The FDA has provided written agreement on the NORSE EIGHT trial protocol and statistical analysis plan under a Special Protocol Assessment (SPA). This agreement confirms that if successful, the trial would satisfy the FDA's requirement for a second adequate and well-controlled clinical trial to address the clinical deficiency identified in the previously received Complete Response Letter (CRL).
Addressing the Unmet Need
ONS-5010/LYTENAVA™ is being developed to address a significant gap in retinal care. Currently, no FDA or European Commission approved ophthalmic formulations of bevacizumab are available. Clinicians treating retinal patients with bevacizumab must use repackaged intravenous bevacizumab that is authorized for different therapeutic indications and provided by compounding pharmacies—products with known risks of contamination and inconsistent potency.
If approved, ONS-5010/LYTENAVA™ would provide physicians with an authorized option to treat wet AMD and potentially other retinal diseases in the United States, EU, and UK.
Mechanism of Action
Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF). It neutralizes VEGF's biological activity by blocking its binding to receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells.
Following intravitreal injection, this binding prevents VEGF from interacting with its receptors, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina—key factors in the progression of wet AMD.
Financial Position and Outlook
For the fiscal second quarter ended March 31, 2024, Outlook Therapeutics reported a net loss attributable to common stockholders of $114.3 million, or $8.01 per basic and diluted share. The adjusted net loss, excluding warrant-related expenses and changes in fair value of warrants and convertible promissory notes, was $22.1 million.
The company recently strengthened its financial position through private placements of common stock and accompanying warrants, generating upfront gross proceeds of $65 million. Additionally, Outlook Therapeutics has the potential to receive up to $107 million in additional gross proceeds upon the full cash exercise of the warrants issued in these placements.
As of March 31, 2024, the company had cash and cash equivalents of $47.2 million. Lawrence Kenyon, Chief Financial Officer, stated, "We believe we are well positioned financially to continue executing on NORSE EIGHT enrollment, resubmission of the ONS-5010 BLA by the end of calendar 2024, and launch of ONS-5010 in 2025, if approved."
Commercialization Strategy
If ONS-5010/LYTENAVA™ receives regulatory approval, Outlook Therapeutics plans to commercialize it directly in the US. For Europe and other regions outside the US, the company is assessing both direct commercialization and partnership opportunities.
As part of its commercial planning, Outlook Therapeutics has entered into a strategic agreement with Cencora to expand its reach to retina specialists and their patients. Cencora will provide third-party logistics services, distribution, and pharmacovigilance services in the United States, EU, and UK.
The company is currently planning for potential commercial launches in the EU and UK beginning in the first quarter of 2025, with a possible US launch later that year, pending FDA approval.
Looking Ahead
Outlook Therapeutics has outlined several key anticipated milestones:
- European Commission decision on the MAA for ONS-5010 expected in Q2 2024
- Full enrollment of the NORSE EIGHT clinical trial in the US expected in Q3 2024
- Topline readout of NORSE EIGHT planned for Q4 2024
- Resubmission of the ONS-5010 BLA to the FDA targeted for the end of 2024
- Potential commercial launches in the EU and UK beginning in Q1 2025
- Potential FDA approval of ONS-5010 in 2025
With these developments, Outlook Therapeutics is positioning ONS-5010/LYTENAVA™ to potentially become the first and only European Commission, MHRA, or FDA-approved ophthalmic formulation of bevacizumab for treating retinal diseases, addressing a significant unmet need in ophthalmology.
