Core Insights - Shares of Outlook Therapeutics (OTLK) fell by 54.1% following the FDA's issuance of a second complete response letter (CRL) rejecting the biologics license application (BLA) resubmission for ONS-5010 in the treatment of wet age-related macular degeneration (wet AMD) [1][7]. Regulatory Developments - The CRL highlighted a single deficiency: insufficient evidence of efficacy, as ONS-5010 did not meet the primary efficacy endpoint in the NORSE EIGHT study, necessitating additional confirmatory data for approval [2][7]. - The FDA's first CRL in 2023 raised concerns regarding chemistry, manufacturing, and controls, which were later addressed by the company [3]. - The NORSE EIGHT study, which was a follow-up to the initial BLA based on the NORSE TWO study, failed to meet the pre-specified non-inferiority endpoint at week 8 [9]. Company Performance - Year-to-date, OTLK shares have decreased by 42.3%, contrasting with a 3.3% growth in the industry [4]. - Following the second regulatory setback, the company plans to meet with the FDA to clarify the requirements for potential approval of ONS-5010 as the first on-label bevacizumab product for intravitreal use in the U.S. [10]. Market Expansion - ONS-5010 received regulatory approval in the EU and the UK in 2024, marketed under the brand name Lytenava for treating wet AMD [12]. - The company launched Lytenava in the UK and Germany in June 2025, positioning it as the first authorized ophthalmic formulation of bevacizumab for wet AMD treatment in these regions [13]. - Outlook Therapeutics aims to provide a regulated alternative to off-label repackaged Avastin (bevacizumab), which is not approved for ophthalmic use [11][13].