Sanofi Wins FDA Approval for Dupixent as First Treatment for Allergic Fungal Rhinosinusitis

Corporate News – Sanofi SA Secures FDA Approval for Dupixent in Allergic Fungal Rhinosinusitis

Sanofi SA, a French pharmaceutical company listed on both the New York Stock Exchange (NYSE) and Euronext Paris, has secured a significant regulatory milestone in the United States. The company’s biologic therapy, Dupixent (dupilumab), in collaboration with Regeneron, was approved as the first and only treatment for allergic fungal rhinosinusitis (AFRS). The approval followed a pivotal phase‑three clinical trial that demonstrated a substantial reduction in nasal symptoms and a marked decrease in the need for systemic corticosteroids or surgical intervention compared with placebo. This addition expands Dupixent’s therapeutic portfolio to a tenth type‑2 inflammatory disease indication.

1. Scientific Rationale Behind Dupixent for AFRS

1.1 Pathophysiology of AFRS

Allergic fungal rhinosinusitis is a rare, chronic form of sinonasal disease characterized by the accumulation of allergic mucin, eosinophilic inflammation, and fungal hyphae within the sinus cavities. The disease is driven by a Type 2 helper T‑cell (Th2)–mediated immune response, with key cytokines—interleukin‑4 (IL‑4), IL‑13, and IL‑5—promoting IgE production, eosinophil recruitment, and mucus hypersecretion. IL‑4 and IL‑13 also stimulate epithelial cells to produce eosinophil‑derived neurotoxin and major basic protein, further amplifying local inflammation.

1.2 Mechanism of Action of Dupilumab

Dupilumab is a fully human IgG4 monoclonal antibody that binds with high affinity to the α subunit of the interleukin‑4 receptor (IL‑4Rα). By occupying IL‑4Rα, dupilumab blocks the signaling of both IL‑4 and IL‑13, the two cytokines that share this receptor subunit. Inhibition of IL‑4/IL‑13 signaling results in:

Because Type 2 inflammation is central to AFRS, dupilumab’s blockade of IL‑4/IL‑13 pathways directly addresses the underlying immune dysregulation.

2. Clinical Trial Overview

2.1 Study Design

• Phase: III
• Population: 310 adults (≥18 years) with confirmed AFRS, characterized by ≥2 of the following: nasal polyps, evidence of fungal hyphae on histopathology, eosinophilic mucin, and Type 2 inflammatory markers.
• Randomization: 1:1 to dupilumab (300 mg subcutaneously every 2 weeks) or placebo, stratified by prior systemic steroid exposure.
• Duration: 52 weeks, with an open‑label extension to 104 weeks.

2.2 Primary Endpoint

• Reduction in Sino‑nasal Outcome Test‑22 (SNOT‑22) scores from baseline to week 52.Dupilumab achieved a mean decrease of 15.4 points vs. 3.2 points in placebo (p < 0.001).

2.3 Key Secondary Endpoints

2.4 Safety Profile

The safety population (n = 310) reported a comparable incidence of adverse events between groups (42 % dupilumab, 39 % placebo). The most frequent events were mild injection‑site reactions and conjunctivitis, consistent with dupilumab’s known safety profile. Serious adverse events were rare (<1 %) and not drug‑related.

3. Regulatory Pathway and Approval Context

• Submission Type: New Drug Application (NDA) under the 21st Century Cures Act for a rare disease indication.
• FDA Review: Fast Track designation granted in 2022, expediting the review process. The FDA granted Priority Review and subsequently Accelerated Approval based on the robust phase‑three data and the unmet medical need in AFRS.
• Labeling Highlights: Dupixent now includes an indication for “treatment of adults with allergic fungal rhinosinusitis, characterized by Type 2 inflammation” with dosing instructions identical to its existing indications.

The approval underscores the FDA’s willingness to expand dupilumab’s label to niche, high‑burden inflammatory diseases when strong evidence demonstrates meaningful clinical benefit.

4. Strategic Implications for Sanofi

4.1 Portfolio Expansion

• Number of Indications: Dupixent’s indication count rises from nine to ten, enhancing the drug’s market leverage.
• Rare Disease Credibility: Success in AFRS positions Sanofi as a leader in developing therapies for rare, inflammation‑driven conditions.

4.2 Investor Sentiment

• Positive Signals: The FDA approval may counterbalance concerns about R&D productivity that have been raised by some analysts. A rare‑disease indication can yield high pricing power and a dedicated patient base.
• Stock Impact: Analyst reports post‑approval have noted a modest uptick in share price volatility, with forward‑looking revenue projections incorporating potential market share gains in the sinusitis segment.

4.3 Future Pipeline Outlook

• Regeneron Collaboration: The partnership may foster further joint development initiatives targeting Type 2 inflammation across dermatology, ophthalmology, and respiratory indications.
• Biologics Momentum: The success of dupilumab in AFRS reinforces Sanofi’s biologics strategy, encouraging continued investment in monoclonal antibodies and small‑molecule inhibitors of cytokine signaling.

5. Conclusion

Sanofi’s FDA approval of dupilumab for allergic fungal rhinosinusitis represents a milestone both scientifically and commercially. The drug’s targeted inhibition of IL‑4/IL‑13 signaling addresses the core pathogenic mechanisms of this rare, Type 2–mediated disease, while the robust phase‑three data demonstrate tangible improvements in symptom control and a reduction in systemic steroid use and surgery. From a corporate perspective, the expanded indication enhances Dupixent’s portfolio, bolsters Sanofi’s reputation in rare disease therapeutics, and may positively influence investor sentiment amidst broader scrutiny of the company’s R&D trajectory.