Regeneron Pharmaceuticals and Sanofi announced that a phase 2a proof-of-concept study of dupilumab, an investigational therapy that blocks IL-4 and IL-13 signaling, met all primary and secondary endpoints in patients with moderate-to-severe chronic sinusitis with nasal polyps (CSwNP) who did not respond to intranasal corticosteroids.
"These data suggest the potential of dupilumab for use in the treatment of another allergic inflammatory condition," said Gianluca Pirozzi, M.D., PhD, vice president, Global Project Head at Sanofi. "Based on these results, we plan to move forward with further clinical development of dupilumab in patients with chronic sinusitis with nasal polyps, in addition to the ongoing development in atopic dermatitis and in asthma."
In the study, dupilumab resulted in a statistically-significant improvement in the size of nasal polyps, as measured by endoscopic Nasal Polyp Score (NPS), the primary endpoint of the study. Statistically significant improvements in all secondary efficacy endpoints were also observed, including objective measures of sinusitis by CT scan, nasal air flow, and patient-reported symptoms (sense of smell, congestion, postnasal drip, runny nose and sleep disturbance). In a pre-specified exploratory analysis, dupilumab-treated patients who also had asthma demonstrated significant improvements in asthma control. The safety profile was consistent with previous studies. The most common AEs with dupilumab were injection site reactions, nasopharyngitis, oropharyngeal pain, epistaxis, headache and dizziness.
"There is growing recognition that patients suffering from one type of allergic disease often have additional allergic conditions. For example, many patients with chronic sinusitis with nasal polyps also have asthma or atopic dermatitis and vice versa," said Neil Graham, M.D., vice president, Programme Management at Regeneron. "The new data reported today, together with prior Phase 2 data with dupilumab in asthma and atopic dermatitis, support the growing body of scientific evidence that these conditions may result from a core allergic inflammatory process driven by the IL-4/IL-13 pathway."
The randomised, double-blind, placebo-controlled study enrolled 60 adult patients with moderate-to-severe CSwNP. Patients in the study received 300 milligrams (mg) of dupilumab or placebo administered once per week (QW) subcutaneously for 16 weeks, following an initial loading dose of 600 mg. All patients in the study also received a standard-of-care nasal corticosteroid spray. Patients were eligible for the study if they continued to have severe CSwNP despite standard treatment for at least one month. Fifty percent of patients in the study had received prior surgery for their condition.
Asthma was also present in 58 per cent of CSwNP patients in the study. The conditions are often co-morbid and symptoms/exacerbations are frequently interdependent. Detailed results of the study will be presented at an upcoming medical conference.
Dupilumab, a fully-human monoclonal antibody, is directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation.
Dupilumab was created using Regeneron's pioneering VelocImmune technology and is being co-developed with Sanofi in atopic dermatitis, asthma and CSwNP. Dupilumab is an investigational agent under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
CSwNP causes mucosal inflammation and polyps in the nasal cavity and sinuses, which result in long-term symptoms of nasal obstruction and congestion, reduction in or loss of sense of smell, and facial pain. Nasal polyps can block normal drainage from the sinuses and patients with nasal obstruction related to nasal polyposis have a 2-fold higher risk of sleep dysfunction. About 75 per cent of CSwNP patients have a decreased sense of smell. The estimated prevalence of CSwNP is 3 per cent to 5 per cent (in Europe and US), and many patients do not respond to the only currently available therapy (intranasal corticosteroids). In the US, approximately 200,000 CSwNP patients have sinus surgery to improve breathing, nasal drainage and remove inflamed mucosal tissue. CSwNP is often associated with asthma. Approximately 30 per cent of patients with CSwNP have asthma.