Just over one month until its Prescription Fee Drug User Act (PDUFA) deadline, Aldeyra Therapeutics disclosed that a late-cycle review meeting with the FDA regarding 0.25% reproxalap ophthalmic solution (reproxalap) identified major issues with the drug’s clinical data.
Quick, give me a refresher on this candidate.
The investigational new drug candidate is Aldeyra’s first-in-class, small-molecule modulator of reactive aldehyde species (RASP).
RASP is known to be elevated in ocular and systemic inflammatory disease as well as cause decreased tear production, eye redness, change in lipid tear composition, and increased ocular inflammation.
To note, the FDA accepted a new drug application (NDA) for reproxalap earlier this year for the treatment of dry eye disease (DED).
How quickly can it work?
Per previous study data, reproxalap has illustrated signs of activity ranging from within minutes of administration to up to 12 weeks.
Speaking of data, what’s been shown so far?
Reproxalap’s NDA submission was based on data from its performance in five well-controlled clinical trials. See here for the details.
In February 2023, Aldeyra reported positive topline data from a 12-month safety trial that illustrated statistically superior visual acuity (VA) improvements.
And most recently—in June 2023—topline data from a phase 3 trial found that reproxalap-treated patients demonstrated a statistically significant reduction in ocular itching score across all 11 pre-specified primary endpoint comparisons (p < 0.001 for each).
Similarly, for the secondary endpoint, reproxalap patients exhibited a statistically significant reduction from baseline versus vehicle (p = 0.004).
Gotcha. So … why the murkiness?
According to Aldeyra, the agency raised concerns regarding the adequacy of clinical evidence for reproxalap’s indication during a recent late-cycle meeting with the FDA.
Additional data was also requested on the drug’s chemistry, manufacturing, and controls (CMC) processes. To note, these are crucial to meet when developing new pharmaceutical products in order to ensure product safety and consistency.
So what exactly does this mean?
In the words of Aldeyra, the FDA, “may not be in the position to approve the NDA for reproxalap by the PDUFA deadline of November 23, 2023.”
What else do we know?
The company has reportedly submitted additional clinical data materials to fulfill the agency’s concerns; however, it has not yet received word on if this data is sufficient.
Further, according to Aldeyra, the FDA has requested for an additional trial to confirm the efficacy of reproxalap.
Yikes. So what’s some potential scenarios here?
First things first, that PDUFA deadline next month won’t be met and the agency will not approve Aldeyra’s NDA, as previously anticipated.
Secondly, the company could potentially receive a complete response letter (CRL), meaning the company would need to provide additional materials (data, analysis, clinical studies) on reproxalap in order for it to be considered for potential approval.
To note, this would cause a major delay in market approval.
Wait, didn’t Aldeyra already receive a similar request?
Yes, but not for reproxalap.
In June 2023, the company received word from the FDA that more clinical data evidence was needed on its NDA submission for ADX-2191 (intravitreal methotrexate 0.8%) for primary vitreoretinal lymphoma (PVRL). Read our coverage on that here.
So what’s next?
Now we wait for further updates on this …
In the meantime, though, Aldeyra’s stock value dropped significantly on Monday following this news, falling +66% by the end of the day ($5.42 to $1.80). See here for its current value.