The injectable biologic dupilumab (Dupixent, Regeneron Pharmaceuticals, Inc and Sanofi) received FDA approval for the treatment of adults with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
“People with moderate to severe atopic dermatitis cope with intense, sometimes unbearable symptoms that can impact them for most of their lives,” said Julie Block, president and chief executive officer, National Eczema Association (NEA). “To date, there have been few options available to treat people with moderate to severe atopic dermatitis who have uncontrolled disease. That’s why this approval of Dupixent is so important for our community. Now we have a treatment that is expected to help address patients coping with this life-altering disease.”
Dupilumab is a human monoclonal antibody that is designed to specifically inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD. The medication comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupilumab can be used with or without topical corticosteroids (TCS). However, it should not be used in patients who are pregnant or breastfeeding or allergic to dupilumab or any of the ingredients in the product.
Cost Considerations
The wholesale acquisition cost (WAC) of dupilumab in the United States is $37,000 annually. Actual costs to patients, payers, and health systems are anticipated to be lower as WAC pricing does not reflect discounts, rebates, or patient assistance programs, according to the companies.
Peter Lio, MD, who practices at Medical Dermatology Associates of Chicago and also serves on the Scientific Advisory Board for the NEA, noted that there has been a lot of discussion about the cost of medications, and he said, there is no doubt that dupilumab is expensive. “However, when we think about the target group: adult patients with moderate to severe atopic dermatitis who are either still struggling with the current best treatments or overusing topical and sometimes even systemic corticosteroids, it becomes clear that the relief from suffering and quality of life improvements from dupilumab are worth it, especially considering the price of biologic agents for psoriasis,” he said.
“Perhaps more importantly, dupilumab offers hope for the patients who are most miserable with AD: those who are missing work and school for weeks and months, those hospitalized with frequent skin infections, and those who have not had a good night’s sleep in months or even years, and that is something worth celebrating,” he said, adding that this drug will mostly be used by specialists.
“My sense is that most physicians will never write [a prescription for] this medication at all; the type of patient who is appropriate for dupilumab treatment is usually referred to a specialist and are those who are either using or considering systemic treatments such as cyclosporine, methotrexate, and phototherapy. That said, it’s important that dermatologists and allergists in particular are aware of it and know how and when to use it, as we will likely be called upon in those difficult cases where it will be most helpful,” Dr Lio said.
Article continues on page 2
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Patient Support Program
Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi, market dupilumab in the United States, which became available at the end of March. The companies have launched DUPIXENT MyWay, a specialized program that provides support and services to patients during the treatment process. The program also will help eligible patients who are uninsured, lack coverage, or need assistance with their out-of-pocket costs. The program offers personalized support from registered nurses and other specialists who are available 24/7 to speak with patients and help them navigate the insurance process.
Clinical Trials
The approval of dupilumab was based on data from the global LIBERTY AD clinical program, which included 3 randomized phase 3 pivotal trials known as SOLO 1, SOLO 2, and CHRONOS (total enrolled 2119 adult patients). The studies examined the use of dupilumab either alone (SOLO 1 or SOLO 2—1379 adult patients enrolled) or with topical TCS (CHRONOS—740 adult patients enrolled) in patients with inadequately controlled moderate to severe AD. In all these studies, dupilumab alone or with TCS met the primary and key secondary endpoints. In the SOLO 1 and SOLO 2 studies, treatment with dupilumab as monotherapy significantly improved measures of skin clearing and overall extent and severity of disease. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 38% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved clear or almost clear skin as measured by the 5-point Investigator’s Global Assessment (IGA) scale (primary endpoint) compared to 10% and 9% with placebo.1-3
At 16 weeks, for SOLO 1 and SOLO 2, respectively, 51% and 44% of patients who received dupilumab 300 mg every 2 weeks achieved a 75% or greater reduction in their Eczema Area and Severity Index score (EASI 75) from baseline, a key secondary endpoint, compared to 15% and 12% with placebo. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 41% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved a ≥4-point improvement in the daily intensity of patient-reported itch, as measured by the Pruritus Numerical Rating Scale compared to 12% and 10% with placebo.1
In the CHRONOS study, treatment with dupilumab with TCS significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS. At 16 weeks, 39% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 12% of patients receiving placebo with TCS. At 16 weeks, 69% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved EASI 75 compared to 23% of patients receiving placebo with TCS. At 16 weeks, 59% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved a ≥4-point improvement in the daily intensity of patient-reported itch compared to 20% of patients receiving placebo with TCS.2
The study also met additional key secondary endpoints at 52 weeks, showing that 36% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 13% of patients receiving placebo with TCS.2
The most common adverse events that were noted to be ≥1% with dupilumab treatment included injection site reactions, eye and eye lid inflammation including redness, swelling, and itching, and cold sores in the mouth or on the lips.1-3
The regulatory agency evaluated dupilumab with Priority Review, which is reserved for medicines that represent potentially significant improvements in safety or efficacy in treating serious conditions. This followed the FDA’s 2014 Breakthrough Therapy designation for dupilumab for inadequately controlled moderate to severe AD. Breakthrough Therapy designation was created by the FDA to expedite the development and review of drugs developed for serious or life-threatening conditions. Dupilumab is the first time this designation was granted for a dermatologic disease, other than in dermatologic cancers.
“FDA’s approval of dupilumab demonstrates our commitment to approving new and innovative therapies for patients with skin disease,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Eczema can cause significant skin irritation and discomfort for patients, so it is important to have a variety of treatment options available to patients, including those patients whose disease is not controlled by topical therapies.”
Other Studies
Dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (6 months to 11 years of age) and adolescents with moderate to severe AD (12-17 years of age), according to the companies. In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.
Dupilumab is also being studied in other inflammatory diseases that are thought to be driven by IL-4 and IL-13 cytokines, including persistent uncontrolled asthma (phase 3, results expected later this year), nasal polyposis (phase 3), and eosinophilic esophagitis (phase 2).
References
1. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016; 375(24):2335-2348.
2. Blauvelt A, Gooderham M, Foley P, et al. Long-term management of moderate-to-severe atopic dermatitis (AD) with dupilumab and concomitant topical corticosteroids (TCS): a 1-year, randomized, placebo-controlled phase 3 trial (CHRONOS). Presented at 2017 American Academy of Dermaotlogy Meeting; March 3-7, 2017; Orlando, Fl.
3. Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2017.
The injectable biologic dupilumab (Dupixent, Regeneron Pharmaceuticals, Inc and Sanofi) received FDA approval for the treatment of adults with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
“People with moderate to severe atopic dermatitis cope with intense, sometimes unbearable symptoms that can impact them for most of their lives,” said Julie Block, president and chief executive officer, National Eczema Association (NEA). “To date, there have been few options available to treat people with moderate to severe atopic dermatitis who have uncontrolled disease. That’s why this approval of Dupixent is so important for our community. Now we have a treatment that is expected to help address patients coping with this life-altering disease.”
Dupilumab is a human monoclonal antibody that is designed to specifically inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD. The medication comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupilumab can be used with or without topical corticosteroids (TCS). However, it should not be used in patients who are pregnant or breastfeeding or allergic to dupilumab or any of the ingredients in the product.
Cost Considerations
The wholesale acquisition cost (WAC) of dupilumab in the United States is $37,000 annually. Actual costs to patients, payers, and health systems are anticipated to be lower as WAC pricing does not reflect discounts, rebates, or patient assistance programs, according to the companies.
Peter Lio, MD, who practices at Medical Dermatology Associates of Chicago and also serves on the Scientific Advisory Board for the NEA, noted that there has been a lot of discussion about the cost of medications, and he said, there is no doubt that dupilumab is expensive. “However, when we think about the target group: adult patients with moderate to severe atopic dermatitis who are either still struggling with the current best treatments or overusing topical and sometimes even systemic corticosteroids, it becomes clear that the relief from suffering and quality of life improvements from dupilumab are worth it, especially considering the price of biologic agents for psoriasis,” he said.
“Perhaps more importantly, dupilumab offers hope for the patients who are most miserable with AD: those who are missing work and school for weeks and months, those hospitalized with frequent skin infections, and those who have not had a good night’s sleep in months or even years, and that is something worth celebrating,” he said, adding that this drug will mostly be used by specialists.
“My sense is that most physicians will never write [a prescription for] this medication at all; the type of patient who is appropriate for dupilumab treatment is usually referred to a specialist and are those who are either using or considering systemic treatments such as cyclosporine, methotrexate, and phototherapy. That said, it’s important that dermatologists and allergists in particular are aware of it and know how and when to use it, as we will likely be called upon in those difficult cases where it will be most helpful,” Dr Lio said.
Article continues on page 2
{{pagebreak}}
Patient Support Program
Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi, market dupilumab in the United States, which became available at the end of March. The companies have launched DUPIXENT MyWay, a specialized program that provides support and services to patients during the treatment process. The program also will help eligible patients who are uninsured, lack coverage, or need assistance with their out-of-pocket costs. The program offers personalized support from registered nurses and other specialists who are available 24/7 to speak with patients and help them navigate the insurance process.
Clinical Trials
The approval of dupilumab was based on data from the global LIBERTY AD clinical program, which included 3 randomized phase 3 pivotal trials known as SOLO 1, SOLO 2, and CHRONOS (total enrolled 2119 adult patients). The studies examined the use of dupilumab either alone (SOLO 1 or SOLO 2—1379 adult patients enrolled) or with topical TCS (CHRONOS—740 adult patients enrolled) in patients with inadequately controlled moderate to severe AD. In all these studies, dupilumab alone or with TCS met the primary and key secondary endpoints. In the SOLO 1 and SOLO 2 studies, treatment with dupilumab as monotherapy significantly improved measures of skin clearing and overall extent and severity of disease. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 38% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved clear or almost clear skin as measured by the 5-point Investigator’s Global Assessment (IGA) scale (primary endpoint) compared to 10% and 9% with placebo.1-3
At 16 weeks, for SOLO 1 and SOLO 2, respectively, 51% and 44% of patients who received dupilumab 300 mg every 2 weeks achieved a 75% or greater reduction in their Eczema Area and Severity Index score (EASI 75) from baseline, a key secondary endpoint, compared to 15% and 12% with placebo. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 41% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved a ≥4-point improvement in the daily intensity of patient-reported itch, as measured by the Pruritus Numerical Rating Scale compared to 12% and 10% with placebo.1
In the CHRONOS study, treatment with dupilumab with TCS significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS. At 16 weeks, 39% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 12% of patients receiving placebo with TCS. At 16 weeks, 69% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved EASI 75 compared to 23% of patients receiving placebo with TCS. At 16 weeks, 59% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved a ≥4-point improvement in the daily intensity of patient-reported itch compared to 20% of patients receiving placebo with TCS.2
The study also met additional key secondary endpoints at 52 weeks, showing that 36% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 13% of patients receiving placebo with TCS.2
The most common adverse events that were noted to be ≥1% with dupilumab treatment included injection site reactions, eye and eye lid inflammation including redness, swelling, and itching, and cold sores in the mouth or on the lips.1-3
The regulatory agency evaluated dupilumab with Priority Review, which is reserved for medicines that represent potentially significant improvements in safety or efficacy in treating serious conditions. This followed the FDA’s 2014 Breakthrough Therapy designation for dupilumab for inadequately controlled moderate to severe AD. Breakthrough Therapy designation was created by the FDA to expedite the development and review of drugs developed for serious or life-threatening conditions. Dupilumab is the first time this designation was granted for a dermatologic disease, other than in dermatologic cancers.
“FDA’s approval of dupilumab demonstrates our commitment to approving new and innovative therapies for patients with skin disease,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Eczema can cause significant skin irritation and discomfort for patients, so it is important to have a variety of treatment options available to patients, including those patients whose disease is not controlled by topical therapies.”
Other Studies
Dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (6 months to 11 years of age) and adolescents with moderate to severe AD (12-17 years of age), according to the companies. In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.
Dupilumab is also being studied in other inflammatory diseases that are thought to be driven by IL-4 and IL-13 cytokines, including persistent uncontrolled asthma (phase 3, results expected later this year), nasal polyposis (phase 3), and eosinophilic esophagitis (phase 2).
References
1. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016; 375(24):2335-2348.
2. Blauvelt A, Gooderham M, Foley P, et al. Long-term management of moderate-to-severe atopic dermatitis (AD) with dupilumab and concomitant topical corticosteroids (TCS): a 1-year, randomized, placebo-controlled phase 3 trial (CHRONOS). Presented at 2017 American Academy of Dermaotlogy Meeting; March 3-7, 2017; Orlando, Fl.
3. Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2017.
The injectable biologic dupilumab (Dupixent, Regeneron Pharmaceuticals, Inc and Sanofi) received FDA approval for the treatment of adults with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
“People with moderate to severe atopic dermatitis cope with intense, sometimes unbearable symptoms that can impact them for most of their lives,” said Julie Block, president and chief executive officer, National Eczema Association (NEA). “To date, there have been few options available to treat people with moderate to severe atopic dermatitis who have uncontrolled disease. That’s why this approval of Dupixent is so important for our community. Now we have a treatment that is expected to help address patients coping with this life-altering disease.”
Dupilumab is a human monoclonal antibody that is designed to specifically inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD. The medication comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupilumab can be used with or without topical corticosteroids (TCS). However, it should not be used in patients who are pregnant or breastfeeding or allergic to dupilumab or any of the ingredients in the product.
Cost Considerations
The wholesale acquisition cost (WAC) of dupilumab in the United States is $37,000 annually. Actual costs to patients, payers, and health systems are anticipated to be lower as WAC pricing does not reflect discounts, rebates, or patient assistance programs, according to the companies.
Peter Lio, MD, who practices at Medical Dermatology Associates of Chicago and also serves on the Scientific Advisory Board for the NEA, noted that there has been a lot of discussion about the cost of medications, and he said, there is no doubt that dupilumab is expensive. “However, when we think about the target group: adult patients with moderate to severe atopic dermatitis who are either still struggling with the current best treatments or overusing topical and sometimes even systemic corticosteroids, it becomes clear that the relief from suffering and quality of life improvements from dupilumab are worth it, especially considering the price of biologic agents for psoriasis,” he said.
“Perhaps more importantly, dupilumab offers hope for the patients who are most miserable with AD: those who are missing work and school for weeks and months, those hospitalized with frequent skin infections, and those who have not had a good night’s sleep in months or even years, and that is something worth celebrating,” he said, adding that this drug will mostly be used by specialists.
“My sense is that most physicians will never write [a prescription for] this medication at all; the type of patient who is appropriate for dupilumab treatment is usually referred to a specialist and are those who are either using or considering systemic treatments such as cyclosporine, methotrexate, and phototherapy. That said, it’s important that dermatologists and allergists in particular are aware of it and know how and when to use it, as we will likely be called upon in those difficult cases where it will be most helpful,” Dr Lio said.
Article continues on page 2
{{pagebreak}}
Patient Support Program
Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi, market dupilumab in the United States, which became available at the end of March. The companies have launched DUPIXENT MyWay, a specialized program that provides support and services to patients during the treatment process. The program also will help eligible patients who are uninsured, lack coverage, or need assistance with their out-of-pocket costs. The program offers personalized support from registered nurses and other specialists who are available 24/7 to speak with patients and help them navigate the insurance process.
Clinical Trials
The approval of dupilumab was based on data from the global LIBERTY AD clinical program, which included 3 randomized phase 3 pivotal trials known as SOLO 1, SOLO 2, and CHRONOS (total enrolled 2119 adult patients). The studies examined the use of dupilumab either alone (SOLO 1 or SOLO 2—1379 adult patients enrolled) or with topical TCS (CHRONOS—740 adult patients enrolled) in patients with inadequately controlled moderate to severe AD. In all these studies, dupilumab alone or with TCS met the primary and key secondary endpoints. In the SOLO 1 and SOLO 2 studies, treatment with dupilumab as monotherapy significantly improved measures of skin clearing and overall extent and severity of disease. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 38% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved clear or almost clear skin as measured by the 5-point Investigator’s Global Assessment (IGA) scale (primary endpoint) compared to 10% and 9% with placebo.1-3
At 16 weeks, for SOLO 1 and SOLO 2, respectively, 51% and 44% of patients who received dupilumab 300 mg every 2 weeks achieved a 75% or greater reduction in their Eczema Area and Severity Index score (EASI 75) from baseline, a key secondary endpoint, compared to 15% and 12% with placebo. At 16 weeks, for SOLO 1 and SOLO 2, respectively, 41% and 36% of patients who received dupilumab 300 mg every 2 weeks achieved a ≥4-point improvement in the daily intensity of patient-reported itch, as measured by the Pruritus Numerical Rating Scale compared to 12% and 10% with placebo.1
In the CHRONOS study, treatment with dupilumab with TCS significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS. At 16 weeks, 39% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 12% of patients receiving placebo with TCS. At 16 weeks, 69% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved EASI 75 compared to 23% of patients receiving placebo with TCS. At 16 weeks, 59% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved a ≥4-point improvement in the daily intensity of patient-reported itch compared to 20% of patients receiving placebo with TCS.2
The study also met additional key secondary endpoints at 52 weeks, showing that 36% of patients who received dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin (IGA 0 or 1) compared to 13% of patients receiving placebo with TCS.2
The most common adverse events that were noted to be ≥1% with dupilumab treatment included injection site reactions, eye and eye lid inflammation including redness, swelling, and itching, and cold sores in the mouth or on the lips.1-3
The regulatory agency evaluated dupilumab with Priority Review, which is reserved for medicines that represent potentially significant improvements in safety or efficacy in treating serious conditions. This followed the FDA’s 2014 Breakthrough Therapy designation for dupilumab for inadequately controlled moderate to severe AD. Breakthrough Therapy designation was created by the FDA to expedite the development and review of drugs developed for serious or life-threatening conditions. Dupilumab is the first time this designation was granted for a dermatologic disease, other than in dermatologic cancers.
“FDA’s approval of dupilumab demonstrates our commitment to approving new and innovative therapies for patients with skin disease,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Eczema can cause significant skin irritation and discomfort for patients, so it is important to have a variety of treatment options available to patients, including those patients whose disease is not controlled by topical therapies.”
Other Studies
Dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (6 months to 11 years of age) and adolescents with moderate to severe AD (12-17 years of age), according to the companies. In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.
Dupilumab is also being studied in other inflammatory diseases that are thought to be driven by IL-4 and IL-13 cytokines, including persistent uncontrolled asthma (phase 3, results expected later this year), nasal polyposis (phase 3), and eosinophilic esophagitis (phase 2).
References
1. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016; 375(24):2335-2348.
2. Blauvelt A, Gooderham M, Foley P, et al. Long-term management of moderate-to-severe atopic dermatitis (AD) with dupilumab and concomitant topical corticosteroids (TCS): a 1-year, randomized, placebo-controlled phase 3 trial (CHRONOS). Presented at 2017 American Academy of Dermaotlogy Meeting; March 3-7, 2017; Orlando, Fl.
3. Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2017.
