Aldeyra suggests potential FDA rejection imminent for dry eye med after 'substantive review issues'

A clear-eyed assessment from Aldeyra Therapeutics indicates its dry eye disease med reproxalap could soon face rejection after “substantive review issues” were identified in a recent meeting with U.S. regulators. 

The company disclosed Monday that a late-cycle review meeting with the FDA included what regulators believe is a lack of clinical evidence to support the drug's approval indication. The biotech was also asked for additional data on reproxalap's chemistry, manufacturing and controls process.

As a result, the company says the FDA “may not be in the position to approve the NDA for reproxalap” by the agency's Nov. 23 review deadline and that Aldeyra may receive a complete response letter. Shares of the company took a tumble as a result, falling more than 66% from $5.43 to $1.80. 

Aldeyra said it has submitted additional materials to assuage the concerns but that the FDA isn’t legally obligated to include the details in its review, and it has not yet “directly opined on the sufficiency of the information submitted.” To make matters more difficult—or at least costly—-the FDA has also advised that Aldeyra conduct an additional trial to confirm efficacy. 

The update negates the biotech’s decision last year to switch up the primary endpoint of a phase 3 trial in patients with dry eye disease so that success would be measured by tear production versus ocular redness. Aldeyra originally failed the trial when assessing redness reduction but hit on tear production, which was then the secondary endpoint. The company planned to submit data to the FDA on ocular redness, dryness and tear production. 

With the dry indication now especially murky, reproxalap’s potential mainly rests as a potential treatment for allergic conjunctivitis. Phase 3 results released in June found a statistically significant reduction compared to placebo in a score measuring eye itchiness among patients exposed to an allergen chamber between 110 minutes and 210 minutes. Patients given reproxalap also had improvements in eye redness compared to placebo. 

The global allergic conjunctivitis market is about half of the dry eye disease market, however, reflected in investors’ response Monday. Grand View Research found that the global dry eye disease market was $5.53 billion in 2022, while Fortune Business Insights puts the global allergic conjunctivitis market at $2.74 billion.