A Review of Dupilumab

Dupilumab (Dupixent), manufactured by Sanofi SA Pharmaceuticals Inc, was initially approved by the FDA on March 28, 2017, via the priority review process reserved for medications that represent potentially significant improvements in safety or efficacy in treating serious conditions. Dupilumab is indicated for the treatment of patients 12 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or in instances in which those therapies are not advisable. It can be used with or without topical corticosteroids.¹

On October 22, 2018, dupilumab was approved as an add-on maintenance treatment in patients 12 years and older with moderate to severe asthma with an eosinophilic phenotype or with oral corticosteroid—dependent asthma. On March 8, 2019, it was approved for chronic rhinosinusitis with nasal polyposis (CRSwNP) as an add-on maintenance treatment in adult patients with inadequately controlled CRSwNP. Dupilumab is the first biologic medicine approved for this indication.²

TREATMENT OF CRSWNP

CRSwNP often occurs with severe asthma and requires systemic steroids or nasal surgery, the current standard of care. However, uncontrolled CRSwNP can lead to debilitating symptoms, including breathing difficulties, nasal congestion and discharge, reduced or loss sense of smell and taste, and facial pressure.

The approval in this indication was based on efficacy and safety data for dupilumab from 2 clinical studies: 24-week SINUS-24 and 52-week SINUS-52. The trial program included 724 patients 18 years and older with CRSwNP who were symptomatic despite taking intranasal corticosteroids. For the studies, patients received dupilumab 300 mg every 2 weeks with standard-of-care mometasone furoate nasal spray (MFNS) compared with a placebo injection plus MFNS.²

Overall, patients treated with dupilumab achieved statistically significant improvements in all primary and secondary end points at 24 weeks in SINUS-24 and SINUS-52, respectively²:

• 57% and 51% improvement in their nasal congestion and obstruction severity compared with 19% and 15% with placebo.
• 33% and 27% reduction in their nasal polyps score compared with 7% and 4% increases with placebo.
• 42% and 27% improvement in sinus opacification compared with 4% and 0% with placebo.
• 52% and 45% improvement in loss of smell compared with 12% and 10% improvements for placebo.

Additionally, a prespecified pooled analysis of the 2 trials up to 52 weeks showed that dupilumab significantly reduced systemic corticosteroid use and the need for sino-nasal surgery compared with placebo. Overall, the proportion of patients who required systemic corticosteroids fell by 74% with dupilumab compared with placebo, and those who required surgery decreased by 83% with dupilumab compared with placebo.²

“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 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, current standards of care,” George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, said in a statement.² “Importantly, many patients with CRSwNP also suffer from asthma, and Dupixent was shown to improve lung function.”

Fifty-nine percent of patients in the trial also had comorbid asthma. These patients demonstrated improvements in lung function that were similar to the patients in the dupilumab asthma program, according to the data. Dupilumab is administered by subcutaneous injection with a 300-mg prefilled syringe for patients with CRSwNP every other week at different injection sites.

MECHANISM OF ACTION

Dupilumab is a human monoclonal antibody that inhibits IL-4 and IL-13 proteins. By inhibiting these proteins, inflammatory responses, such as redness, itching, and swelling, are mitigated.³

DOSAGE AND ADMINISTRATION

Dupilumab is available as a prefilled syringe and should be stored in the refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect the medication from light. It may be administered by the patient via subcutaneous injection approximately 45 minutes after it has been removed from the refrigerator, in order for it to reach room temperature. The injection should be administered into the thigh or abdomen, except for the 2 inches around the navel. Injection sites should be rotated consistently to avoid complications such as bruising and scarring.³

WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS

The most common adverse reactions observed during clinical trials for atopic dermatitis with Dupixent included injection-site reactions, oral herpes, and various eye conditions (conjunctivitis, blepharitis, eye pruritus, and dry eye). Warnings and precautions associated with dupilumab also include hypersensitivity and keratitis, as well as telling patients to not adjust or stop taking their asthma medication in conjunction with Dupixent unless instructed to do so by their physician.¹

In CRSwNP, the most common adverse effects (AEs) reported in the clinical trials were injection-site reactions, conjunctivitis, arthralgia, and gastritis.² The most serious AEs reported by patients with asthma using dupilumab were allergic, including anaphylaxis; 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; skin rash; eye problems; and inflammation of blood vessels.³

COST

The wholesale acquisition cost (WAC) of dupilumab in the United States is $3019.50 per 4-week supply. Actual costs to patients, payers, and health systems are anticipated to be lower because the WAC pricing does not reflect discounts, rebates, or patient assistance programs.⁴

References

• Sanofi and Regeneron announce FDA approval of Dupixent (dupilumab), the first targeted biologic therapy for adults with moderate-to-severe atopic dermatitis. Bridgewater, NJ, and Tarrytown, NY: Regeneron and Sanofi; March 28, 2017. www.news.sanofi.us/2017-03-28-Sanofi-and-Regeneron-Announce-FDA-Approval-of-Dupixent-R-dupilumab-the-First-Targeted-Biologic-Therapy-for-Adults-with-Moderate-to-Severe-Atopic-Dermatitis. Accessed July 13, 2019.
• FDA approves Dupixent (dupilumab) for chronic rhinosinusitis with nasal polyposis [news release]. Tarrytown, NY: Regeneron; June 26, 2019. investor.regeneron.com/news-releases/news-release-details/fda-approves-dupixentr-dupilumab-chronic-rhinosinusitis-nasal. Accessed June 26, 2019.
• Dupixent (dupilumab) [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals; 2017.
• FDA approves asthma indication for Dupixent (dupilumab). Regeneron and Sanofi.prnmedia.prnewswire.com/news-releases/fda-approves-asthma-indication-for-dupixent-dupilumab-300734860.html?c=n. Accessed October 22, 2018.
• Dupixent (dupilumab) cost and pricing information. Dupixent website. dupixent.com/dupixent-pricing. Updated June 2019. Accessed July 13, 2019.