Aldeyra Therapeutics: Navigating Regulatory Hurdles and Strategic Alliances in the Race for Dry Eye Disease Approval

Aldeyra Therapeutics' journey toward securing FDA approval for reproxalap (Repro), its investigational dry eye disease (DED) treatment, has been marked by both progress and setbacks. With a Prescription Drug User Fee Act (PDUFA) date set for December 16, 2025Aldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application^[1], the company faces a critical juncture. The recent Complete Response Letter (CRL) from the FDA—issued after Aldeyra's resubmitted New Drug Application (NDA)—underscores the agency's stringent requirements for demonstrating efficacy in DED, a condition plagued by heterogeneity and subjective symptom assessmentAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2]. For investors, the question is whether Aldeyra can navigate these regulatory hurdles while maintaining its competitive edge in a rapidly evolving market.

Regulatory Risks: A Test of Efficacy and Methodology

The FDA's CRL highlighted a recurring issue: the need for “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye”Aldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2]. Aldeyra's resubmission included data from a dry eye chamber trial that met its primary endpoint of reducing ocular discomfortAldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application^[1], but the agency's skepticism persists. The CRL's focus on methodological concerns—such as baseline score discrepancies across treatment arms—suggests the FDA is scrutinizing the robustness of Aldeyra's trial designAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2].

To address this, Aldeyra has initiated two additional trials: a second dry eye chamber study and a six-week field trialAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2]. The company expects top-line results by Q2 2025Aldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2], with plans to resubmit the NDA if outcomes are favorable. However, the path to approval hinges on the FDA's interpretation of these data. A Type A meeting scheduled within 30 days of the CRL's release will be pivotal in aligning expectationsAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2]. For investors, the risk lies in the FDA's potential demand for further trials, which could delay approval and drain Aldeyra's $101 million cash runwayAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2].

Strategic Positioning: AbbVie's Expanded Role and Market Dynamics

Aldeyra's collaboration with AbbVie, a key player in ophthalmology, has been strategically recalibrated. The expanded agreement extends AbbVie's option period to ten business days post-FDA approvalExpansion Side Letter Agreement: Aldeyra & AbbVie Collaboration^[3], granting the biopharma giant greater flexibility to co-develop and commercialize Repro in the U.S. This partnership is critical: AbbVie's deep commercialization expertise could accelerate Repro's market entry, while Aldeyra's financial burden is mitigated by AbbVie's potential assumption of launch costsExpansion Side Letter Agreement: Aldeyra & AbbVie Collaboration^[3].

The dry eye market itself is a double-edged sword. While the $5.8 billion global market is projected to grow at a 6.4% CAGR through 2035Dry Eye Disease Market Size, Growth & Competitive Landscape^[4], it is dominated by artificial tears—a low-margin, first-line therapy. Prescription drugs, however, are gaining traction, driven by evidence linking chronic inflammation to DED progressionDry Eye Disease Market Size, Growth & Competitive Landscape^[4]. Alcon's recent FDA approval of TRYPTYR in 2025Dry Eye Disease Market Size, Growth & Competitive Landscape^[4] and the emergence of in-situ gelling drops and implantable punctal plugs illustrate the competitive landscape's innovation. For Repro to succeed, it must differentiate itself through superior efficacy or convenience—a challenge given the FDA's current skepticism.

Financial and Operational Constraints

Aldeyra's financial position adds another layer of complexity. With $101 million in cash and $6 million in projected 2025 trial costsAldeyra Therapeutics Receives Complete Response Letter from the U.S. Food and Drug Administration for the Reproxalap New Drug Application^[2], the company appears well-positioned to fund its near-term trials. However, a prolonged regulatory process or additional studies could strain resources. The AbbVie agreement's stipulations—such as Aldeyra's responsibility for mid-single-digit million-dollar launch costs without AbbVie's approvalExpansion Side Letter Agreement: Aldeyra & AbbVie Collaboration^[3]—introduce operational risks if the partnership falters.

Risk Reassessment for Investors

For biotech investors, Aldeyra's story is a textbook case of balancing high-reward potential with regulatory uncertainty. The December 2025 PDUFA date represents a binary event: approval could unlock a lucrative partnership with AbbVie and a foothold in a growing market, while another CRL would likely necessitate a capital raise or strategic pivot. The company's ability to address the FDA's methodological concerns—particularly in its upcoming field trial—will be critical.

Moreover, the competitive landscape is shifting. While Aldeyra's mechanism of action (targeting Th17 inflammation) is novel, the market's rapid innovation means Repro must not only gain approval but also secure differentiation in a crowded field. AbbVie's expanded role provides strategic flexibility, but the partnership's success hinges on Repro's regulatory fate.

Conclusion: A High-Stakes Gamble

Aldeyra Therapeutics stands at a crossroads. The December 2025 PDUFA date is a make-or-break moment for Repro, with the FDA's CRL serving as a stark reminder of the agency's high bar for DED treatments. While the company's clinical and strategic moves—additional trials, an expanded AbbVie agreement, and a robust cash position—signal resilience, the path to approval remains fraught with risk. For investors, the key takeaway is clear: Aldeyra's success will depend not only on the strength of its data but also on its ability to navigate the FDA's evolving expectations and outmaneuver a rapidly innovating market.