Dupilumab Receives Priority Review for Severe Chronic Rhinosinusitis with Nasal Polyps Indication

Officials with the FDA have granted Priority Review status to the supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) as an add-on maintenance treatment for adults with inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP), according to a press release.¹

If approved, dupilumab would be the first FDA-approved biologic for the treatment of CRSwNP. CRSwNP is a chronic disease, in which individuals with severe disease typically experience recurrent inflammation of the upper airway despite previous surgery and/or systemic corticosteroids.¹

The sBLA submission is based on data from 2 phase 3 trials, SINUS-24 and SINUS-52, evaluating the efficacy and safety of 300 mg dupilumab every 2 weeks with standard-of-care mometasone furoate nasal spray (MFNS) compared with a placebo injection plus MFNS. Study participants had recurring severe CRSwNP and had been previously treated with surgery and/or systemic corticosteroids. In addition, SINUS-52 included a third patient group who switched from dupilumab every 2 weeks to dupilumab every 4 weeks after week 24. In the trials, approximately 60% of patients had comorbid asthma, with most of them receiving asthma controller medications.¹

Data from these trials were presented at the Annual Meeting of the American Academy of Allergy, Asthma, and Immunology in February 2019.

According to Regeneron, key data from the trial showed:²

• 42% and 27% improvement in sinus opacification versus 4% and 0% with a placebo at 24 weeks in SINUS-24 and SINUS-52, respectively.
• 146% and 108% improvement in ability to identify different smells versus 19% and 7% with placebo at 24 weeks in SINUS-24 and SINUS-52, respectively.
• 60% and 51% improvement in health-related quality of life versus 18% and 18% with placebo at 24 weeks, respectively.
• 0.21L improvement in lung function versus placebo at 24 weeks in SINUS-24 in the subset of patients with asthma at baseline and 0.21L improvement in lung function versus placebo in SINUS-52.
• 73% reduction in rescue treatment with systemic corticosteroids or nasal polyp surgery compared with placebo at 24 weeks SINUS-24 and 76% reduction at 52 weeks in SINUS-52.

In addition, previous topline results announced in October 2018 found that patients treated with dupilumab experienced a:²

• 57% and 51% improvement in their nasal congestion/obstruction severity compared with 19% and 15% improvement with placebo in SINUS-24 and SINUS-52, respectively.
• 33% and 27% reduction in their nasal polyps score compared with a 7% and 4% increase for placebo in SINUS-24 and SINUS-52, respectively

Overall, rates of adverse events (AEs) were similar between the dupilumab-treated group and placebo. Treatment-emergent AEs occurred less frequently in patients treated with dupilumab compared with the placebo group. The most commonly reported AEs in the dupilumab group included nosebleeds and bronchitis in SINUS-24 and cough and injection site reactions in SINUS-52.²

“Dupixent is the first biologic therapy to demonstrate the potential to produce disease-modifying effects in severe CRSwNP, significantly improving all disease measures in the study, including sense of smell, one of the most troublesome and challenging-to-treat symptoms for patients,” Claus Bachert, MD, professor and head of clinics of the department of otorhinolaryngology at Ghent University, said in a previous statement.²

According to Dr Bachert, the study results are particularly promising because they demonstrate dupilumab’s efficacy in patients with both comorbid CRSwNP and asthma, which is often more difficult to treat.²

Dupilumab is currently approved in the United States for the treatment of moderate-to-severe atopic dermatitis and maintenance treatment of moderate-to-severe asthma. In addition to these indications, dupilumab is also being investigated for diseases driven by allergic and other type 2 inflammation.¹

Dupilumab is being jointly developed by Regeneron and Sanofi. The target action date for the FDA decision for this indication is June 26, 2019, according to the release.¹

References

• FDA to Undertake Priority Review of Dupixent (Dupilumab) for Adults with Inadequately Conrolled Severe Chronic Rhinosinusitis with Nasal Polyps [news release]. Regeneron. https://investor.regeneron.com/news-releases/news-release-details/fda-undertake-priority-review-dupixentr-dupilumab-adults. Accessed March 8, 2019.

• Positive Results Presented from Two Phase 3 Trials of Dupixent (Dupilumab) in Severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) [news release]. Regeneron. https://newsroom.regeneron.com/news-releases/news-release-details/positive-results-presented-two-phase-3-trials-dupixentr. Accessed March 8, 2019.