Outlook slumps as FDA rejects eye disease drug

Shares in Outlook Therapeutics cratered today after the FDA rejected the company's marketing application for its lead drug ONS-5010, a therapy for age-related macular degeneration (AMD).

The US regulator issued a complete response letter (CRL) to the New Jersey-based biotech, partly due to "several" manufacturing issues that emerged during pre-approval inspections, but also due to "a lack of substantial evidence".

ONS-5010 is a new ophthalmic formulation of bevacizumab, a VEGF inhibitor originally developed by Roche and sold as Avastin/MabThera, which for years has been used off-label to treat the wet form of AMD, a leading cause of blindness, as a low-cost alternative to approved VEGF therapies like Bayer/Regeneron’s Eylea (aflibercept) and Roche/Novartis’ Lucentis (ranibizumab).

Outlook's stock was down 84% at the time of writing as investors digested the news and tried to gauge whether the programme could be put back on track.

The CRL comes after the company withdrew its first marketing application for ONS-5010 last year, following an FDA request for additional information. It refiled its marketing application last October.

Outlook said the FDA acknowledged that its NORSE TWO pivotal trial "met its safety and efficacy endpoints," which included an improvement in best-corrected visual acuity (BCVA) by 15 letters or more from baseline.

After 11 months, almost 42% of patients on OPNS-5010 met that threshold, compared to 23% of a matched group given Lucentis, which was a statistically significant difference. However, the FDA appears to have decided that it will need another confirmatory study before it will consider approval.

Outlook is already running the NORSE SEVEN trial of ONS-5010 in a pre-filled syringe formulation, expected to be completed in 2024, but as yet it is not clear whether that could serve as confirmation. The company has requested a meeting with the FDA to try to chart a way forward and, in the meantime, ONS-5010 remains under regulatory review in Europe.

According to GlobalData, the use of unapproved repackaged bevacizumab originally intended for intravenous use by compounding pharmacies is estimated to account for approximately 50% of all wet AMD injections in the US each year.

Some studies have suggested, however, that there is considerable variation in drug concentration between different repackaged bevacizumab samples, according to Outlook, which could result in lower efficacy.

ONS-5010 is intended as a standardised version of the drug, which would give those patients an alternative and consistent bevacizumab-based treatment option.

Julia Haller, Outlook board member and ophthalmologist-in-chief at Wills Eye Hospital in Philadelphia, said: "The retina community needs an FDA-approved ophthalmic bevacizumab to deliver an alternative targeted, on-label treatment for patients with wet AMD."