Outlook Therapeutics' second attempt to secure US approval for Lytenava (bevacizumab-vikg) as a treatment for wet age-related macular degeneration (wet AMD) has been hampered by the drug's failure to meet a key endpoint in the Phase III NORSE EIGHT trial (NCT06190093). The company's stock plummeted by over 79% in premarket trading following the release of preliminary topline results.
NORSE EIGHT Trial Results
The NORSE EIGHT study did not meet the pre-specified non-inferiority endpoint at eight weeks, as outlined in the special protocol assessment (SPA) with the US Food and Drug Administration (FDA). Preliminary results showed that the mean change in best corrected visual acuity (BCVA) from baseline to eight weeks was +4.2 letters with Lytenava, compared to a +6.3 letters improvement observed with Roche’s Lucentis (ranibizumab), an FDA-approved wet AMD therapy. However, Outlook Therapeutics noted that the safety profiles of the two therapies were comparable, with similar overall ocular adverse event rates in both groups.
Outlook's Response and Future Plans
Despite the trial's failure to meet its primary endpoint, Outlook Therapeutics intends to proceed with its plans to gain US approval for Lytenava. The company plans to resubmit the biologics license application (BLA) with a complete analysis of the NORSE EIGHT trial in Q1 2025. Outlook Therapeutics emphasized that it has completed the remediation of the chemistry, manufacturing, and controls (CMC) comments outlined in the complete response letter (CRL) issued by the FDA last year.
Previous Regulatory Setbacks
In August 2023, the FDA declined to approve Lytenava as a treatment for wet AMD, citing manufacturing issues and the need for additional confirmatory clinical data. The company intended to address these concerns with data from the NORSE EIGHT trial.
Global Expansion and Partnerships
Looking beyond the US market, Outlook Therapeutics is considering launching Lytenava in the UK and Germany in 2025, where the therapy has already been approved by the European Commission and has marketing authorization from the Medicines and Healthcare products Regulatory Agency (MHRA). The company is also exploring potential partnerships for global markets, excluding the US.
