Outlook Therapeutics Stock Plunges as Wet AMD Drug Falters in Phase III Trial

Outlook Therapeutics' stock has taken a significant hit after its wet Age-Related Macular Degeneration (AMD) drug, ONS-5010, failed to meet the primary endpoint in a Phase III clinical trial. The drug, an ophthalmic formulation of bevacizumab, was compared to Roche's Lucentis in the NORSE EIGHT trial, which aimed to demonstrate non-inferiority after eight weeks.

The trial results showed that while ONS-5010 demonstrated a +4.2 letter improvement in Best-Corrected Visual Acuity (BCVA), it fell short of the primary endpoint compared to Lucentis, which showed a +6.3 letter improvement. Despite the drug's favorable safety profile and evidence of biologic activity, the failure to meet the non-inferiority endpoint has raised concerns among investors.

Market Reaction and Financial Implications

Shares in Outlook Therapeutics fell around 80% in premarket trading following the announcement of the trial results. The significant drop reflects investors' disappointment with the drug's performance and the potential impact on the company's financial projections. With a potential market size of $10 billion for wet AMD treatments in Europe, a 2-year delay in the European launch could result in a revenue loss of up to $2 billion.

Delayed BLA Resubmission and European Launch

Outlook Therapeutics plans to resubmit its Biologics License Application (BLA) for ONS-5010 in the first quarter of 2025. However, the delayed BLA resubmission and postponed European launch to 2025 may impact the company's ability to secure additional funding or partnerships in the future. Competitors could gain market share during this period, further exacerbating concerns about the drug's market potential.

Expert Opinions and Path Forward

Despite the setback, Outlook Therapeutics remains optimistic about ONS-5010's potential. The drug's +4.2 letter improvement in vision, biologic activity, and favorable safety profile could still attract patients seeking affordable, on-label alternatives to off-label bevacizumab (Avastin) or other anti-VEGF therapies. To mitigate the risks associated with the delayed BLA resubmission and European launch, Outlook Therapeutics must address these setbacks transparently, present a compelling roadmap for future development, and engage with investors and potential partners to build confidence in the company's long-term prospects.

As the wet AMD treatment landscape remains competitive, the success of ONS-5010 will depend on its ability to demonstrate clinical benefits and cost-effectiveness compared to existing therapies. The positive attributes of the drug, combined with the company's ability to secure European and UK marketing authorization for LYTENAVA™, may help it gain some traction in these markets. However, the delayed BLA resubmission and European launch could present challenges in maintaining investor confidence and attracting new partnerships.