FDA Approves Dupilumab as Additional Maintenance Therapy in Certain Children with Asthma

The FDA has approved dupilumab (Dupixent^®, Regeneron and Sanofi) in patients with moderate-to-severe asthma aged 12 years and older.¹ The medication’s new approval indicates it’s use as an add-on maintenance therapy with an eosinophilic phenotype or with oral corticosteroid-dependent asthma, according to Regeneron and Sanofi.¹

Dupilumab inhibits the overactive signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), 2 key proteins that contribute to the Type 2 inflammation that may underlie moderate-to-severe asthma. This effect is associated with the reduction of inflammatory biomarkers including fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) and eotaxin-3 (CCL26).¹

According to George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer of Regeneron, Dupixent has now been approved by the FDA for 2 important groups of uncontrolled asthma patients— those who are moderate-to-severe with an eosinophilic phenotype or those with oral corticosteroid-dependent asthma.¹

"In the asthma clinical trial program, Dupixent reduced severe exacerbations and oral corticosteroid use, improved quality of life and showed statistically significant and clinically meaningful improvements in lung function,” said Yancopoulos, in a prepared statement.¹

Efficacy and safety of dupilumab in patients with moderate-to-severe asthma aged 12 years and older was determined through a pivotal trial program that evaluated 2,888 adult and adolescent patients with moderate-to-severe asthma. These patients were studied in 3 randomized, placebo-controlled, multicenter trials (Trial 1, Trial 2 and Trial 3) for 6 months to 1 year (24 to 52 weeks). All trials enrolled patients irrespective of minimum baseline eosinophil levels.¹

In Trial 2 (the largest trial), dupilumab reduced exacerbations and improved lung function in the overall population. Benefits in exacerbations were seen in patients with eosinophil counts greater than or equal to 150 cells/microliter, which represented 70% of the patients enrolled. Efficacy improved in patients with higher eosinophil counts. For example, in patients with blood eosinophils of 300 cells/microliter or greater, dupilumab reduced severe exacerbations by 67% compared to placebo, and improved FEV₁ (lung function) by 29%-33% compared to 14%-16% for placebo. In patients with eosinophil counts less than 150 cells/microliter, there was no difference in severe exacerbation rates for dupilumab versus placebo.¹

In Trial 3, which evaluated severe, oral corticosteroid-dependent patients, dupilumab reduced average daily oral corticosteroid use by 70% compared to 42% with placebo. More than half of patients treated with dupilumab completely eliminated use of oral corticosteroids. Effects on lung function and on oral steroid and exacerbation reduction were similar for dupilumab irrespective of baseline blood eosinophil levels.

In the asthma clinical trials, the adverse reactions that occurred with dupilumab at a rate of at least 1% and more frequently than the respective comparator were injection site reactions, sore throat, and an increase in the number of eosinophils, a type of white blood cell, in the blood.¹

Yancopoulos also noted recently announced positive Phase 3 clinical trial results for treating chronic rhinosinusitis with nasal polyps with dupilumab (CRSwNP).¹ The SINUS-24 (n=276) and SINUS-52 (n=448) trials studied the drug’s treatment for adults with inadequately-controlled CRSwNP, and both studies met all primary and secondary endpoints.²

Positive Topline Results Shown for Dupilumab in Phase 3 Trials in Patients with CRSwNP

“We are committed to advancing our broad development program in additional Type 2 inflammatory diseases,” Yancopoulos said, in his statement.¹

Olivier Brandicourt, MD, Chief Executive Officer, Sanofi, said dupilumab has also made a difference for many adults with atopic dermatitis, and the FDA’s most recent approval for Dupixent marks a significant development for some patients with moderate-to-severe asthma aged 12 years and older.¹

"For patients dependent on oral corticosteroids, Dupixent improved lung function, reduced oral corticosteroid use and reduced exacerbations regardless of baseline eosinophil levels," said Brandicourt, in a prepared statement.¹ "Despite the spectrum of treatments for asthma, there continues to be an unmet need for so many patients with moderate-to-severe asthma, and given that Dupixent works differently than other biologics, there is now a new treatment option for some of these patients."

Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA), expressed support for new indications for dupilumab in a prepared statement. He said the AAFA supports the availability of innovative new treatment options for people with asthma who struggle with uncontrolled symptoms that impair their quality of life. "Despite being compliant with their current medicine, many people with moderate-to-severe asthma, including those with eosinophilic phenotype or with oral steroid dependence, live with persistent symptoms like unpredictable attacks and difficulty breathing," said Mendez, in the statement.¹

For people with asthma, Dupixent comes in 2 doses (200 mg and 300 mg) given every other week at different injection sites after an initial loading dose.¹

According to the Regeneron and Sanofi, patients with moderate-to-severe asthma often have uncontrolled, persistent symptoms despite standard-of-care therapy that may make them suitable for treatment with a biologic therapy. They live with coughing, wheezing and difficulty breathing, and are at risk of severe asthma attacks that may require emergency room visits or hospitalizations. Oral corticosteroids can provide relief for severe, short-term symptoms, but their chronic use is limited to the most severe patients, due to the potential for serious adverse effects.¹

The most serious adverse effects reported by patients using dupilumab are allergic reactions, including anaphylaxis, as well as breathing problems, fever, general ill feeling, swollen lymph nodes, swelling of the face, mouth and tongue, hives, itching, fainting, dizziness, low blood pressure, joint pain, or skin rash; eye problems, and inflammation of blood vessels.¹

The most common side effects include injection site reaction, pain in the throat and cold sores in the mouth or on lips. Eye and eyelid inflammation, including redness, swelling and itching have been seen in patients who have atopic dermatitis.¹

In the United States, Dupixent was approved by the FDA in 2017 with Priority Review and Breakthrough Therapy designations. Dupixent was indicated in its approval for treating adult patients with moderate-to-severe eczema that is not well controlled with topical prescription therapies, or who cannot use therapies on the skin.³

FDA Accepts Dupilumab sBLA for Treatment of Asthma

Reference

• FDA Approves Asthma Indication for Dupixent® (dupilumab) [news release]. Tarrytown, NY and Paris, France; October 22, 2018: Regeneron and Sanofi. https://prnmedia.prnewswire.com/news-releases/fda-approves-asthma-indication-for-dupixent-dupilumab-300734860.html?c=n. Accessed October 22, 2018.
• Dupixent® (dupilumab) showed positive topline results in two Phase 3 trials of patients with chronic rhinosinusitis with nasal polyps [news release]. Paris and Tarrytown, NY; October 16, 2018: Sanofi Media Relations and Regeneraon Media Relations. https://prnmedia.prnewswire.com/news-releases/dupixent-dupilumab-showed-positive-topline-results-in-two-phase-3-trials-of-patients-with-chronic-rhinosinusitis-with-nasal-polyps-300731314.html?c=n. Accessed October 16, 2018.
• FDA approves new eczema drug Dupixent [news release]. Silver Spring, MD: March 28, 2017: FDA website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549078.htm. Accessed October 16, 2018.