Outlook Therapeutics’ eye disease drug has failed to match Roche’s Lucentis in a key trial. The biotech brushed off the failure, noting positive details and vowing to seek FDA approval, but investors were less sanguine about the setback.
New Jersey-based Outlook ran the trial to address some of the issues that led the FDA to reject its first attempt to win approval last year. The agency’s concerns with the prior filing included “a lack of substantial evidence,” Outlook said. Based on feedback from the FDA, the biotech designed a study to compare the effect of its drug candidate ONS-5010 with Lucentis after eight weeks.
ONS-5010 only needed to perform as well as Lucentis to hit the primary endpoint, but it failed to clear that bar. After eight weeks, wet age-related macular degeneration (AMD) patients taking Lucentis had gained 6.3 letters on the BCVA eye test, compared to 4.2 letters for their peers on ONS-5010.
Outlook obtained a written agreement on the trial protocol and statistical analysis plan from the FDA under a special protocol assessment (SPA) in January. The SPA said a successful study would satisfy the FDA’s requirement for a second adequate and well-controlled clinical trial.
The trial wasn’t successful but Outlook still plans to resubmit its application for approval when it wraps up its analysis of the final results in the first quarter of 2025. Outlook countered the primary endpoint miss by stating “the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile.”
ONS-5010 is an ophthalmic version of bevacizumab, the anti-VEGF antibody that Roche sells as Avastin in cancer indications. There is a long history of off-label use of bevacizumab in the treatment of AMD and a head-to-head trial found it was equivalent to Lucentis in the setting in 2011. Lucentis is more expensive than Avastin, fueling interest in the off-label use of Avastin in AMD.
Outlook is betting that there is a market for an on-label bevacizumab. Russell Trenary, the biotech’s CEO, outlined the thinking at an investor event in September, arguing that “a lack of potency, safety concerns or quality and supply issues” cause physicians to switch to other drugs after starting patients on off-label Avastin. Outlook has tried to address the issues with a production process tailored to use in the eye.
Shares in Outlook fell around 80% to below $1 in premarket trading.