Outlook Therapeutics, Inc. (OTLK) has announced positive results from its NORSE EIGHT clinical trial, evaluating ONS-5010/LYTENAVA (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD). The study met its non-inferiority endpoint compared to ranibizumab (Lucentis) at week 12, paving the way for a planned BLA resubmission in Q1 2025. This development offers a potential new treatment option for patients suffering from this leading cause of vision loss.
The NORSE EIGHT trial was a randomized, controlled, masked study designed to assess the efficacy and safety of ONS-5010 in patients with newly diagnosed wet AMD. Participants were randomized in a 1:1 ratio to receive either 1.25 mg of ONS-5010 or 0.5 mg of ranibizumab via intravitreal injections at day 0, week 4, and week 8, with a final visit at week 12. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 8.
Visual Acuity and Retinal Thickness Results
While ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8, the 12-week data demonstrated statistically significant results. The difference in the mean BCVA between ONS-5010 and ranibizumab was -1.009 letters, with a 95% confidence interval of (-2.865, 0.848). In the intent-to-treat (ITT) population, the ONS-5010 arm showed a mean improvement of 5.5 letters in BCVA, while the ranibizumab arm showed a 6.5 letter improvement.
Additionally, changes in central retinal thickness, a key measure of anatomical response, were similar in both study arms across all time points. Specifically, ONS-5010 demonstrated mean visual acuity improvements of +3.3 letters at week 4, +4.2 letters at week 8, and +5.5 letters at week 12.
Safety and Tolerability
ONS-5010 was generally well-tolerated, with overall ocular adverse event rates comparable to ranibizumab. Importantly, the safety results were consistent with previous NORSE trials (ONE, TWO, and THREE), with no cases of retinal vasculitis reported in either study arm.
Expert Commentary
"The 3-month data from NORSE EIGHT provides additional evidence to confirm what retina specialists expected," commented Julia A. Haller, MD, Ophthalmologist-in-Chief at Wills Eye Hospital and an Outlook Therapeutics Board member. "The clinical trial continues to demonstrate that ONS-5010 injections result in immediate and sustained anatomic efficacy, with steady gains in visual acuity and reliable, consistent safety."
Path to Regulatory Approval and Commercialization
Outlook Therapeutics is preparing to resubmit the BLA for ONS-5010 to the FDA in the first quarter of calendar 2025. LYTENAVA (bevacizumab gamma), the same formulation as ONS-5010, has already received marketing authorization in the European Union and the United Kingdom, with a commercial launch planned for the first half of 2025. The company believes that ONS-5010/LYTENAVA could provide an important therapy for wet AMD, offering a regulated alternative to off-label bevacizumab.
Financial Considerations
To support its clinical development programs and the European commercial launch of LYTENAVA, Outlook Therapeutics has entered into agreements for warrant inducement transactions, expected to result in up to $20.4 million in gross proceeds. The company reported a net loss of $75.4 million for the fiscal year 2024 and had cash and cash equivalents of $14.9 million as of September 30, 2024.
