Aldeyra Therapeutics, Inc. announced that the FDA has accepted for review its new drug application (NDA) resubmission for 0.25% reproxalap ophthalmic solution (reproxalap), a potential treatment for dry eye disease (DED).
Take note: This acceptance is take two for the company, as it previously faced FDA concerns over its original NDA last year.
Give me the rundown on reproxalap.
The company’s flagship product candidate is a small-molecule modulator of reactive aldehyde species (RASP), a class of molecules typically elevated in ocular and systemic inflammatory disease (more on that in a moment).
Keep in mind: RASPs are also known to cause:
- Decrease in tear production
- Conjunctival hyperemia
- Change in lipid tear composition
- Increased ocular inflammation
For Aldyera: The company’s RASP Modulator Platform is designed to target a family of small protein-binding molecules that, in turn, enable them to simultaneously determine the activity and structure of multiple proteins.
And reproxalap’s mechanism of action (MOA)?
Prior DED clinical data on the candidate has found it to demonstrate signs of activity beginning within minutes of topical administration to up to 12 weeks.
Specifically: Aldeyra has reported reproxalap is “the first investigational drug with pivotal data supportive of acute and chronic activity in reducing (DED) symptoms.”
- To note: It’s currently under clinical investigation for both DED and allergic conjunctivitis (AC).
Gotcha. Now what other clinical data is available on the candidate?
Between its DED and AC proposed indications, reproxalap has been evaluated for safety and efficacy in +2,000 patients across five clinical studies (for DED) and, just last year, a phase 3 study for AC.
Zeroing in on the most recent study: Just this past August, the company reported positive phase 3 data from a dry eye chamber crossover study—with reproxalap found to be well tolerated and achieving the primary outcome:
- Ocular discomfort from 80 to 100 minutes in the dry eye chamber—and was found to be well tolerated.
- See those details, including common adverse events (AEs).
Now address the elephant in the room—why the need for an NDA resubmission?
As we said last month, when reporting on Aldeyra’s resubmission of this application, it’s easier to give you a timeline.
- February 2023: The FDA accepted Aldeyra’s original NDA for reproxalap
- A Prescription Fee Drug User Act (PDUFA) deadline was set for Nov. 23, 2023.
- October 2023: The agency identified substantive review issues following a late-cycle review meeting with Aldeyra on the drug’s study data (see here for details) from their clinical trials
- FDA requested more data on its chemistry, manufacturing, and controls (CMC) processes.
- November 2023: The company received a company response letter from the FDA with concerns over the candidate’s adequacy of clinical evidence for its indication
- Per the agency: Reproxalap’s NDA failed to demonstrate efficacy for treating ocular symptoms associated with dry eye.
- Also: At least one additional adequate and well-controlled study is needed to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.
- Then: Aldeyra submitted a special protocol assessment (SPA) for a dry eye chamber crossover trial on reproxalap (as we noted above).
That’s quite the journey. Anything else to note?
Yes, actually … prior to Aldeyra receiving that company response letter in November 2023, the company announced that it and AbbVie, Inc. had entered into an exclusive option agreement for reproxalap’s DED indication.
While it was placed on the back burner for the last year, that agreement is still happening—with expansions, to boot.
Refresh me on that deal.
For AbbVie: The company has the option to acquire a co-license for the U.S. development, manufacturing, and commercialization of reproxalap—as well as the exclusive license for those rights in countries outside of the United States.
For Aldeyra: The company will receive a $1 million non-refundable opinion fee plus an upfront payment of $100 million fewer option fees (based on whether AbbVie uses its option).
Both companies: Will also share profits and losses (60% and 40% for AbbVie and Aldeyra, respectively) from reproxalap’s commercialization.
- Plus: Outside the U.S. market, Aldeyra would be eligible to receive tiered royalties on net sales of the product.
See our complete coverage, including Aldeyra’s eligibility for milestone payments.
And what’s this new expansion?
Based on the FDA’s NDA acceptance, Aldeyra reported that it will initiate certain “pre-commercial activities, 60% of which will be paid by AbbVie and 40% of which will be paid by Aldeyra if the option is exercised.”
- As for AbbVie: The company is said to have already “independently” initiated certain pre-commercial planning activities.
Both companies have also agreed to "amend the expiration of the option (for AbbVie) to 10 business days” from reproxalap’s DED FDA approval date.
Speaking of dates … when will we know if the FDA approves this new NDA?
The federal agency has issued a Prescription Drug User Fee Act (PDUFA) date of April 2, 2025.
Here’s hoping the second time’s the charm!