The FDA ( U.S. Food and Drug Administration ) has approved Dupixent ( Dupilumab ) for use with other medicines to treat chronic rhinosinusitis with nasal polyposis ( CRSwNP ) in adults whose disease is not controlled.
CRSwNP can be a debilitating condition, with many patients opting for systemic steroids or nasal surgery which often cannot control this disease.
Moreover, CRSwNP often occurs in combination with severe asthma.
Dupixent is the first FDA approved medicine for adults with chronic rhinosinusitis with nasal polyposis, and the only approved therapy shown to shrink nasal polyp size and also improve the signs and symptoms of the associated chronic rhinosinusitis.
In fact, approximately three-quarters of patients treated with Dupixent no longer required either corticosteroids or surgery, the current standards of care.
Many patients with CRSwNP also suffer from asthma, and Dupilumab was shown to improve lung function in these patients as well.
Dupixent is a fully-human monoclonal antibody that inhibits the signalling of interleukin-4 ( IL-4 ) and interleukin-13 ( IL-13 ), two proteins that play a central role in type 2 inflammation.
Data from Dupilumab clinical trials have shown that inhibiting IL-4 and IL-13 helps address the type 2 inflammation that plays a major role in CRSwNP, asthma and atopic dermatitis.
CRSwNP is a chronic disease of the upper airway that obstructs the sinuses and nasal passages. It can lead to breathing difficulties, nasal congestion and discharge, reduced or loss of sense of smell and taste, and facial pressure.
Many patients with CRSwNP have other type 2 inflammatory diseases like asthma, and these patients often have more severe asthma and are often more difficult to treat.
In the Dupixent CRSwNP clinical trials, 59% of patients also had asthma.
These co-morbid diseases can lead to an increased risk of asthma attacks, high symptom burden and a substantial adverse impact on health-related quality of life.
The FDA approval is based on two pivotal trials ( the 24-week SINUS-24 and 52-week SINUS-52 ) that are part of the phase 3 LIBERTY clinical trial program.
These trials have evaluated Dupilumab 300 mg every two weeks with standard-of-care Mometasone furoate nasal spray ( MFNS ) compared to placebo injection plus MFNS.
In these trials, Dupilumab significantly improved key disease measures and met all primary and secondary endpoints.
At 24 weeks, patients treated with Dupilumab achieved statistically significant improvements in all primary and secondary endpoints, including:
57% and 51% improvement in their nasal congestion / obstruction severity compared to a 19% and 15% improvement with placebo in SINUS-24 and SINUS-52, respectively ( least squares LS mean change from baseline of -1.34 and -1.25 for Dupilumab compared to -0.45 and -0.38 for placebo; difference between Dupilumab and placebo: -0.89 and -0.87 );
33% and 27% reduction in their nasal polyps score compared to a 7% and 4% increase with placebo in SINUS-24 and SINUS-52, respectively ( LS mean change from baseline of -1.89 and -1.71 for Dupilumab compared to 0.17 and 0.10 for placebo; difference between Dupilumab and placebo: -2.06 and -1.80 ).
Secondary endpoints include:
42% and 27% improvement in sinus opacification compared to 4% and 0% with placebo in SINUS-24 and SINUS-52, respectively ( LS mean change from baseline of -8.18 and -5.21 for Dupixent compared to -0.74 and -0.09 for placebo );
52% and 45% improvement in loss of smell compared to a 12% and 10% improvement with placebo in SINUS-24 and SINUS-52, respectively ( LS mean difference in Dupilumab compared to placebo of -1.12 and -0.98 in SINUS-24 and SINUS-52, respectively ).
In pre-specified pooled analyses of the two trials up to 52 weeks, Dupilumab treatment resulted in a significant reduction of systemic corticosteroid use and the need for sino‑nasal surgery compared to placebo.
The proportion of patients who required systemic corticosteroids was reduced by 74% with Dupilumab compared to placebo.
The proportion of patients who required sino-nasal surgery was reduced by 83% with Dupilumab compared to placebo.
In the 59% of patients who also had asthma, the improvements in lung function were similar to patients in the Dupixent asthma program.
Treatment effects on nasal congestion and loss of smell were observed with the first assessment as early as 4 weeks and showed continued improvement for the duration of the trial.
In the 52 week SINUS-52 trial, patients continued to do well through the 52 week treatment period.
In the CRSwNP clinical trials, adverse events that occurred in at least 2% of Dupilumab patients and greater than placebo were injection site reactions ( 6% Dupilumab, 4% placebo ), conjunctivitis ( 2% Dupilumab, 1% placebo ), arthralgia ( 3% Dupilumab, 2% placebo ) and gastritis ( 2% Dupilumab, 1% placebo ).
Dupixent comes in a 300 mg pre-filled syringe for patients with CRSwNP. It is given as a subcutaneous injection every other week at different injection sites.
Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional.
In addition to chronic rhinosinusitis with nasal polyposis, Dupixent is approved in the U.S. for use with other asthma medicines for the maintenance treatment of moderate-to-severe asthma in certain patients aged 12 years and older whose asthma is not controlled with their current asthma medicines; and to treat patients aged 12 years and older with moderate-to-severe atopic dermatitis ( eczema ) that is not well controlled with prescription therapies used on the skin ( topical ), or who cannot use topical therapies.( Xagena )
Source: Sanofi, 2019