On 31 December 2025, Outlook Therapeutics announced that the FDA issued a Complete Response Letter (CRL) regarding the second resubmission of its Biologics Licence Application (BLA) for its ophthalmic formulation of bevacizumab, ONS-5010/Lytenava™, for wet AMD.
The CRL comes 7 weeks after the FDA accepted Outlook’s second resubmission of its BLA for Lytenava™ in November 2025. In the CRL, the FDA indicated that the mechanistic and natural history data added in the BLA resubmission did not alter its earlier assessment. While the FDA acknowledged that the single adequate and well-controlled study demonstrated efficacy, it again recommended that additional confirmatory evidence be provided to support the application, though did not clarify what type of evidence would be acceptable.
Bob Jahr, CEO of Outlook Therapeutics, stated that while Outlook is “disappointed and disagree[s] with this decision”, they are “fully committed to taking all necessary steps to receive approval in the United States”.
Outlook Therapeutics received a first CRL from the FDA for Lytenava™ in August 2023 and subsequently submitted a Special Protocol Assessment request in December 2023 regarding further clinical trials. It resubmitted its BLA to the FDA in February 2025 based on positive results of the NORSE EIGHT clinical trial, announced in January 2025. A second CRL (issued in August 2025) recommended that Outlook submit additional efficacy data to support its application for Lytenava™. Outlook resubmitted its BLA to the FDA for a second time in early November 2025.
Lytenava™ was approved in the EU in May 2024 and was launched in the UK and Germany for wet AMD in June 2025. The Scottish Medicines Consortium accepted Lytenava™ for use within NHS Scotland in June 2025.
Intas Pharmaceuticals reportedly has an ophthalmic bevacizumab biosimilar under development, having received approval from India’s CDSCO in March 2025 to conduct Phase 2/3 trials of bevacizumab (solution for intravitreal injection 25mg/mL) in patients with wet AMD.