FDA denies Outlook’s wet AMD bid, issues Complete Response Letter

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FDA denies Outlook’s wet AMD bid, issues Complete Response Letter

Published: Aug 30, 2023

By Tristan Manalac


The FDA on Wednesday rejected Outlook Therapeutics’ investigational ophthalmic bevacizumab solution ONS-5010, which the company was proposing as a treatment for wet age-related macular degeneration.

In its Complete Response Letter, the regulator flagged “several CMC issues” as well as other concerning observations during pre-approval manufacturing inspections. The FDA also noted that while ONS-5010 met its primary safety and efficacy endpoints in the Phase III NORSE TWO trial, there was a “lack of substantial evidence” in Outlook’s Biologics License Application (BLA).

The New Jersey biotech doesn’t seem to have given up on ONS-5010 and is planning to request a formal meeting with the FDA “to further understand the BLA deficiencies and how best to resolve them,” CEO Russel Trenary said in a statement.

“Following this meeting with the FDA, the company will be able to discuss next steps and the expected timing for resolution,” Trenary said.

Outlook’s shares dropped 74% in pre-market trading Wednesday in response to the rejection.

Outlook’s BLA contained data from the NORSE clinical development program, including the pivotal NORSE TWO study, which compared ONS-5010 against Genentech’s Lucentis (ranibizumab). The trial met its primary and secondary endpoints, demonstrating that ONS-5010 led to significantly better vision gains.

The BLA also included data from the clinical experience trial NORSE ONE and the open-label safety study NORSE THREE.

ONS-5010’s active ingredient is bevacizumab, a monoclonal antibody sold by Roche’s Genentech under the brand name Avastin. Bevacizumab works by blocking the VEGF signaling protein and disrupts its interaction with its corresponding cell surface receptors, which in turn prevents the growth of new blood vessels.

This mechanism of action has won bevacizumab several approvals in cancer, including colorectal cancer, non-small cell lung cancer and breast cancer. In eye diseases, however, bevacizumab is often used on an off-label basis, meaning the drug is given without the FDA’s specific approval.

Nevertheless, an anti-VEGF approach has already been shown to be effective in wet age-related macular degeneration (AMD). Lucentis and Vabysmo (faricimab), both by Genentech, work along the same pathway—as does Bayer’s Eylea (aflibercept), a blockbuster intravitreal decoy receptor that targets both VEGF and PIGF proteins.

Eylea has a strong hold on the wet AMD market and made around $1.75 billion in sales during the first half of 2023, representing a 1.4% increase from the same period the year prior. Vabysmo is following closely behind, making nearly $1.1 billion in revenue during the first half of this year. Lucentis, on the other hand, lost the protection of its basic primary patents in the U.S. and sustained a nearly 50% drop in sales.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at [email protected] or [email protected].

Source: BioSpace