Dupixent Receives FDA Approval for Expanded Use in Adolescents with Chronic Rhinosinusitis with Nasal Polyps

On September 13 local time, Regeneron and Sanofi announced that the U.S. FDA had approved their drug Dupixent (dupilumab) as an add-on maintenance treatment for adolescents aged 12 to 17 with chronic rhinosinusitis with nasal polyps (CRSwNP) whose condition is not adequately controlled. This approval expands the FDA's initial approval in June 2019 for CRSwNP (as an add-on maintenance treatment for CRSwNP patients aged 18 years and older). Dupilumab is reportedly the first treatment approved by the U.S. FDA for this patient population with CRSwNP.

Since its approval for the first indication (atopic dermatitis) in 2017, dupilumab has been approved globally for a total of seven indications, including the aforementioned one, such as asthma, prurigo nodularis, chronic spontaneous urticaria, and eosinophilic esophagitis. In 2023, global sales of dupilumab reached approximately $11.6 billion, representing a 33% year-over-year increase. In the first half of 2024, dupilumab's sales further rose to about $6.66 billion, surpassing AbbVie's adalimumab ($5.084 billion in H1 sales) and Johnson & Johnson's ustekinumab ($5.336 billion in H1 sales), making it the new "blockbuster drug" in autoimmune diseases.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease associated with elevated levels of eosinophils, a type of white blood cell. It is characterized by increased eosinophil levels, leading to the growth of soft tissue known as nasal polyps. Polyps that block the inner walls of the nasal passages or sinuses may cause chronic symptoms such as nasal congestion, loss of smell, facial pressure, and runny nose.

CRSwNP is one of the common diseases in the field of otorhinolaryngology. According to data from the Chinese Journal of Otorhinolaryngology-Head and Neck Surgery, its global prevalence ranges from 5.5% to 28.0%, with approximately 8.0% in China, where there are over 100 million patients, indicating a significant clinical demand.

The currently recommended treatment regimen includes medical treatment centered on glucocorticoids and surgical treatment focused on functional endoscopic sinus surgery to remove lesions. The first-line treatment drug is intranasal corticosteroids (INCS), but some patients exhibit an inadequate treatment response. The clinical efficacy of using systemic corticosteroids (SCS) for treating CRSwNP is difficult to sustain, and polyp recurrence may occur after discontinuation. As part of the overall treatment for CRS, endoscopic sinus surgery cannot resect or alter the inflammatory nature of the sinus mucosa.

In recent years, biologics represented by monoclonal antibodies targeting type 2 inflammation have entered the field of CRSwNP treatment (IL-4, IL-5, IL-13, IgE, and their receptors). As maintenance adjunctive therapies for adult CRSwNP patients who remain poorly controlled despite INCS treatment, drugs including omalizumab (IgE target), mepolizumab (IL-5 target), and dupilumab (IL-4 target) have been approved and launched, offering new treatment options for patients.

In June 2019, Dupilumab was approved in the United States, becoming the first biologic treatment for CRSwNP (as an add-on maintenance treatment for CRSwNP patients aged 18 years and older).

This approval (for the add-on maintenance treatment of CRSwNP in adolescents aged 12 to 17) expands the FDA's initial approval of CRSwNP in 2019.This approval was supported by data from two positive pivotal trials in adults with inadequately controlled CRSwNP. In the SINUS-24 and SINUS-52 trials, Dupixent (dupilumab) significantly improved nasal congestion/blockage severity, nasal polyp size, and sense of smell over 24 weeks compared to placebo, while also reducing the need for systemic corticosteroids or surgery.

This approval is supported by pharmacokinetic data from adult and adolescent patients aged 12 years and older with moderate to severe asthma, as well as from adult patients with inadequately controlled CRSwNP, and by safety data of Dupixent in adolescents aged 12 years and older with moderate to severe asthma.

Moreover, in the SINUS-24 and SINUS-52 trials, the safety results of Dupixent in adults were generally consistent with the known safety profile of Dupixent in its approved indications. Compared to placebo, in the 24-week safety data from SINUS-24 and SINUS-52, adverse events occurring more frequently (≥1%) with Dupixent included injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.

Dupilumab is a humanized monoclonal antibody targeting IL-4Rα jointly developed by Sanofi and Regeneron.It inhibits IL-4 and IL-13 signaling by specifically binding to the IL-4Rα subunit shared by the interleukin-4 (IL-4) and interleukin-13 (IL-13) receptor complexes, thereby suppressing type 2 inflammatory responses.

IL-4 and IL-13 Mediated Inflammation is a Key Component in the Pathogenesis of Asthma, Atopic Dermatitis, Chronic Rhinosinusitis with Nasal Polyps, Eosinophilic Esophagitis, and Prurigo Nodularis. The inflammation involves various cell types that express IL-4Rα (e.g., mast cells, eosinophils, macrophages, lymphocytes, epithelial cells, goblet cells) and inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines, chemokines). Blocking IL-4Rα with dupilumab can inhibit IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of pro-inflammatory cytokines, chemokines, nitric oxide, and IgE.

It is not difficult to see that Dupilumab has a very broad application space in inflammatory diseases.

Just the day before yesterday (i.e., September 12), Regeneron and Sanofi also announced that dupilumab had achieved both the primary endpoint and key secondary endpoints in clinical trials for the treatment of bullous pemphigoid (BP) and chronic spontaneous urticaria (CSU).If approved, dupilumab will become the first targeted drug in the United States and the European Union for the treatment of BP, bringing new hope to patients with BP and CSU, and broadening the application boundaries of dupilumab in the field of inflammation.

According to incomplete statistics, since its first approved indication (atopic dermatitis) in 2017, dupilumab has been approved for 7 indications, including the aforementioned one, across more than 60 countries and regions worldwide, such as asthma, prurigo nodularis, chronic spontaneous urticaria, eosinophilic esophagitis, and chronic obstructive pulmonary disease. Globally, over one million patients are currently receiving treatment with dupilumab.

In its first year on the market (2017), Dupixent's sales were only 200 million euros, but by 2019, they had rapidly surged to 2.1 billion euros, a tenfold increase in just two years. In 2023, Dupixent's global sales reached approximately $11.6 billion, representing a 33% year-over-year growth. In the first half of 2024, Dupixent’s sales further rose to about $6.66 billion, surpassing AbbVie's Humira (first-half sales of $5.084 billion) and Johnson & Johnson's Stelara (first-half sales of $5.336 billion). In just eight years, it dethroned the previous "blockbuster drug" Humira to become the new top autoimmune "blockbuster drug."

A large market naturally attracts other pharmaceutical companies to enter. In China alone, dozens of pharmaceutical companies, including Hengrui Medicine, Huadong Medicine, Conmed, Zhixiang Jintai, Shijie Group, Kangfang Biotech, 3SBio, Connect Biopharma, Magi Bio, Simcere Pharma, and Quanxin Biotech, have already laid out their strategies in the IL-4Rα field.

Among them, the fastest-progressing is Connaught's Spesolimab. On September 12, Connaught announced that its self-developed Class 1 new drug, Kangyueda (Spesolimab Injection), has officially been approved for marketing by the National Medical Products Administration for the treatment of adult patients with moderate to severe atopic dermatitis. This is the first IL-4Ra antibody drug in China and the second globally to be submitted and approved for marketing, filling the gap in the field of biologics for atopic dermatitis produced in China.

In addition to Connect Biopharma's Spebimab being approved for marketing, several other domestically produced IL-4R monoclonal antibodies have entered Phase III clinical trials, including Connect Biopharma’s Ledebebimab, Quanxin Biotech’s QX005N, Zhi Xiang Jin Tai’s GR1802, 3SBio’s SSGJ-611, Akeso’s Mandebimab, and Hengrui Medicine’s SHR-1819, among others.

It is not difficult to see that in the next two years, several IL-4R monoclonal antibodies will be launched intensively in China. Dupilumab, the "new king" of autoimmune treatments, will also face strong competitors. The excitement is just beginning.

References:

1. 3SBio, "Phase II Clinical Study of 3SBio's Recombinant Anti-IL-4Rα Humanized Monoclonal Antibody Injection (611) for the Treatment of Chronic Rhinosinusitis with Nasal Polyps Meets Primary Endpoint"

2. VBInsight Database, "The Change of the 'King of Autoimmune Drugs': Can Dupilumab Secure Its Throne After Reaching the Top?"