The US Food and Drug Administration (FDA) has once again declined to approve Outlook Therapeutics' ophthalmic version of Roche's Avastin, known as Lytenava (ONS-5010), for the treatment of wet age-related macular degeneration (AMD).This decision marks the second rejection for the drug, which was previously turned down in 2023 due to manufacturing concerns and a lack of confirmatory clinical evidence.
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fiercepharma.comIn a complete response letter issued to Outlook, the FDA highlighted a significant deficiency: the absence of sufficient evidence demonstrating the drug's effectiveness.
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fiercepharma.comFollowing the first rejection, Outlook had agreed to conduct a second phase 3 trial, named Norse Eight, to validate Lytenava's efficacy against Roche and Novartis' Lucentis, an established anti-VEGF agent used for various eye conditions, including wet AMD.
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fiercepharma.comDespite the company's efforts, the Norse Eight trial did not meet its primary endpoint at eight weeks, which raised concerns among analysts and investors.The trial's results indicated that Lytenava led to a mean improvement of 5.5 letters in best corrected visual acuity (BCVA), compared to 6.5 letters for Lucentis.
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fiercepharma.comOutlook's CEO, Bob Jahr, expressed disappointment but emphasized that the FDA's letter did not explicitly request another study, suggesting that the path forward may still be viable.
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fiercepharma.comThe FDA's rejection has had a significant impact on Outlook's stock, which plummeted approximately 52% following the announcement.
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fiercepharma.comAnalysts are now questioning the company's next steps, as the management team has not provided clear answers regarding potential new trials or additional data that could satisfy the FDA's requirements.
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fiercepharma.comOutlook's management plans to engage with the FDA to clarify the agency's expectations and explore possible avenues for approval.The company is hopeful that real-world data could play a role in future submissions, as the FDA has increasingly accepted such data in recent years.
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fiercepharma.comHowever, the specifics of what the FDA will accept as confirmatory evidence remain uncertain.
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fiercepharma.comWet AMD is a leading cause of blindness among older Americans, affecting an estimated 20 million people in the US The condition can lead to rapid vision loss, making effective treatments critical.
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aao.orgAnti-VEGF drugs, including Lucentis and Eylea, have significantly improved outcomes for patients, reducing the incidence of AMD-related blindness by nearly half in some regions.
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aao.orgOutlook's goal is to introduce the first ophthalmic formulation of bevacizumab for intravitreal injection, which would provide consistent dosing and quality assurance compared to the current oncology version used off-label for AMD treatment.
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fiercepharma.comThe company has launched Lytenava in Europe, where it received approval from the European Commission in May 2024, and it began sales in Germany and the UK in June 2025.
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fiercepharma.comAs Outlook navigates this setback, the company is focusing on cash conservation and expanding its commercial presence in Europe, with expectations to maintain sufficient cash reserves until the end of 2025.
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fiercepharma.comThe future of Lytenava remains uncertain, but Outlook's leadership is committed to addressing the FDA's concerns and finding a path forward for the drug.
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fiercepharma.comIn summary, the FDA's rejection of Lytenava for the second time underscores the challenges faced by pharmaceutical companies in bringing new treatments to market, particularly in the competitive landscape of eye disease therapies.The outcome of Outlook's next steps will be closely monitored by investors and healthcare professionals alike as they await further developments in the treatment of wet AMD.
