The US Food and Drug Administration (FDA) has rejected Outlook Therapeutics’ bevacizumab for a second time, meaning the company once again misses out on joining the lucrative wet age-related macular degeneration (wet AMD) market.
Dubbed ONS-5010, Outlook’s bevacizumab is an ophthalmic version of Roche’s blockbuster oncology drug Avantis, with the former company hoping that administering it via intravitreal injection will unlock indications in the retinal disease market.
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The FDA was not so positive in its review, issuing a complete response letter (CRL) for the anti-VEGF agent in the treatment of wet AMD. The agency noted only one, albeit large, deficiency – a “lack of substantial evidence of effectiveness”.
Shares in US-listed Outlook tanked 67% at market open to $0.79 on 28 August from a previous market close of $2.37. The company has a market cap of $48.4m.
The FDA has taken a different path with regulators in Europe and the UK. Outlook’s bevacizumab is approved in both the latter regions under the brand name Lytenava, courtesy of market authorisations in 2024. The company said it will continue to expand into additional markets in Europe.
However, in terms of Outlook’s interactions with the FDA, it marks the second rejection in two years. The agency previously snubbed the drug amid manufacturing concerns and the need for more confirmatory clinical evidence. In light of the decision, Outlook agreed to carry out a second Phase III trial called Norse Eight (NCT06190093).
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By GlobalDataData reported in November 2024 showed that the first Norse Eight trial did not meet its eight-week endpoint. Outlook decided to proceed with the biologics license application (BLA) amid other favourable 12-week data in the trial that compared ONS-5010 with Roche and Novartis’ Lucentis (ranibizumab), a fellow anti-VEGF agent approved in many eye disease indications.
According to Outlook, the FDA specifically highlighted the primary endpoint miss for ONS-5010, even though an original trial – Norse Two – produced positive results. Unlike the previous rejection in 2023, in which Outlook was tasked with conducting another study, the FDA has asked that more confirmatory evidence be submitted.
“While we are very disappointed with this outcome, we intend to meet with the FDA to receive additional clarity on their requirements to potentially approve the first on-label bevacizumab product specifically formulated, manufactured, and packaged for intravitreal use in the US,” said Outlook’s CEO Bob Jahr, who only joined the company in July.
He added that “it is important to also note that the CRL identified no other outstanding deficiencies in our BLA”.
Wet AMD is an eye condition where abnormal vessels grow in the macula. These leak blood or fluid, which leads to a rapid loss of vision. The wet AMD market has gone through significant shifts in recent years, but it has always been dominated by anti-VEGF drugs. Regeneron’s Eylea (aflibercept) franchise has been the top-selling drug in the indication for a while, but the influx of biosimilars has eroded market share. Roche’s Vabysmo (faricimab) has rapidly been gaining market share, with sales reaching $4.87bn in 2024.
The US AMD market, which also includes the more common dry form, was estimated to be worth $4.76bn in 2024. It is forecast to rise to $13.8bn by 2033, according to analysis by GlobalData’s Pharma Intelligence Center.
GlobalData is the parent company of Pharmaceutical Technology.
