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Establishing Links Between Certain Inflammatory Diseases
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Establishing Links Between Certain Inflammatory Diseases

How two companies came together to target a source of type 2 inflammation that may drive asthma, eczema and chronic rhinosinusitis with nasal polyposis.

Many people with certain inflammatory diseases may have more than one. They may suffer from asthma and atopic dermatitis (the most common form of eczema), or asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Over decades, physicians have noted this pattern, and theorized that these conditions might share the same underlying cause.

At the same time, epidemiologists have documented a notable rise in many allergic diseases.1 This rise has been most dramatic in a subset of allergic inflammatory diseases, which have widely varying symptoms, but similar underlying drivers in the immune system.2,3 For example, the prevalence of asthma rose steadily from 1980-2010, according to the U.S. Centers for Disease Control and Prevention (CDC).4,5 Studies also document a steady increase in the prevalence of atopic dermatitis.6 Studies have shown that with an innovative medicine called Dupixent® (dupilumab), three different chronic diseases may be treated by targeting a source of an underlying immune component called type 2 inflammation.7

Created by scientists at Regeneron, who partnered with Sanofi Genzyme to develop the medicine, Dupixent has been approved in the U.S. in certain patients for the treatment of uncontrolled moderate-to-severe atopic dermatitis, and with other medicines for uncontrolled moderate-to-severe eosinophilic or oral steroid dependent asthma and uncontrolled chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupixent is not used to treat sudden breathing problems.8

INDICATIONS

DUPIXENT® (dupilumab) is a prescription medicine used:
  • to treat people aged 6 years and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 years of age.

  • with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in people aged 12 years and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 12 years of age.

  • with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.

IMPORTANT SAFETY INFORMATION

Do not use if you are allergic to dupilumab or to any of the ingredients in Dupixent.

Please scroll down or click here to view full Important Safety Information and Indications

Impact to patients

Atopic dermatitis is the most common form of eczema9
  • This chronic inflammatory disease often appears as an itch and rash on the skin that can crack, crust and ooze.10,11

  • In its moderate-to-severe form, rashes can cover much of the body and people can experience intense, persistent and sometimes debilitating itch.11,12

Asthma is a lower airway disease
  • People with moderate-to-severe asthma often live with coughing, wheezing and difficulty breathing and are also at risk of severe asthma attacks.13

  • Asthma attacks and worsening of symptoms can result in unplanned or urgent medical visits.13,14,15

CRSwNP is an upper airway disease in which tissue growths (nasal polyps) form in the sinus and nasal passages16,17
  • This chronic disease can lead to breathing difficulties, nasal congestion and discharge, reduced or loss of sense of smell and taste, and facial pressure.16,17

  • Standard of care – which includes intranasal and systemic steroids and sinus surgery – may not fully address symptoms of CRSwNP.16

An underlying driver that may be shared

portrait of Jennifer Hamilton

“Although type 2 inflammation may cause different symptoms in different organs, such as itching on the skin or wheezing from the lungs, it’s the same inflammation that could be driving these various diseases. Type 2 inflammation isn’t limited to just one organ or another. That explains why people who have one of these diseases can often have another.”

Jennifer Davidson Hamilton, Ph.D.

Executive director and head of precision medicine at Regeneron

Type 2 inflammation as a shared underlying driver of these diseases may also support a potential explanation for their rising prevalence.2,18 The type 2 immune response helps rid the body of tiny worms and other infectious parasites.7,19 It is because parasites have become so rare in the developed world, researchers theorize, that the type 2 immune response may develop sensitivity to everyday substances to cause type 2 inflammation.2,7,18

“Due to a combination of genetic and environmental factors, the body gets fooled into thinking there are parasites around,” says Naimish Patel, M.D., head of global development, immunology, and inflammation at Sanofi Genzyme. “But there are no parasites. The body ends up chronically fighting itself, sometimes with harmful results.”

Diseases such as atopic dermatitis and asthma can be challenging to control, as chronic symptoms may wax and wane unpredictably.11,13 Some people with severe symptoms may use immunosuppressants such as oral steroids for long periods of time.20,21 Additionally, people with uncontrolled asthma and CRSwNP have an increased risk of emergency room or hospital visits from severe asthma attacks or planned nasal polyp surgery.14,15,22 As the prevalence of these diseases rose through the late 20th century, the need grew for additional treatment options for these conditions.

Dual inhibition with one biologic medicine

The scientific history leading to Dupixent goes back to the 1990s, when academic and government researchers studying the intricate web of cells and molecules involved in the type 2 immune response found two proteins, interleukin-4 (IL-4) and interleukin-13 (IL-13), that play a key part in orchestrating the immune response with distinct, yet overlapping roles.23 In diseases such as atopic dermatitis and certain types of asthma, this immune response is dysregulated and leads to type 2 inflammation. It was then that Regeneron, a fledgling biotechnology company at the time, took on the arduous mission of creating a medicine that would interfere with the activity of both IL-4 and IL-13 to help reduce type 2 inflammation.

“It used to be thought that IL-4 and IL-13 almost totally overlapped in their functions. And they do overlap some, but there are unique roles they play in the inflammatory cascade. So we felt it’s important to hit the activity of both,” Hamilton says.

Scientists at Regeneron found a way to block activity of both proteins by targeting a similarity between them. Although IL-4 and IL-13 are distinct proteins, the structures that they use to interact with cells share one component.25,26 During the 1990s, Regeneron scientists conducted research based on new insights into this shared structure that ultimately led to the discovery of Dupixent. One important aspect of Dupixent is that it is not an immunosuppressant, and it has not been shown to affect the broader immune system.

portrait of Naimish Patel

“You can target two components of the immune response that contributes to the disease without suppressing the other parts of the immune system. That’s really the innovation.”

Naimish Patel, M.D.

Head of global development, immunology, and inflammation at Sanofi Genzyme

After years of lab research, Regeneron partnered with Sanofi Genzyme starting in 2007 to investigate the potential of promising medicines such as Dupixent for appropriate patients.

“We had different strengths that we brought to the table and were laser focused on figuring out how to bring this exciting discovery to patients,” Hamilton says.

Showing clinical evidence

That combination of scientific excellence and strategic capability would be essential to tackle the clinical development needed to support approval in these three diseases. The teams embarked on clinical trials for Dupixent in atopic dermatitis, asthma and CRSwNP. Yet even after years of research and preparation, findings in the studies surprised them – Dupixent had an effect on certain symptoms in atopic dermatitis, asthma and CRSwNP patients as early as two weeks after the first dose.

In a one-year clinical trial of Dupixent with topical steroids compared to topical steroids alone, adults with moderate-to-severe atopic dermatitis taking Dupixent experienced reduced itch as measured at two weeks after the first dose (18% vs. 8% not taking Dupixent).27,28,29 After 16 weeks of Dupixent treatment, over three times more adults saw clearer skin compared to placebo (39% vs. 12% not taking Dupixent) and more than two-thirds saw at least 75% skin improvement (69% vs. 23% not taking Dupixent).8 The improvements were sustained at 52 weeks.8 The most common side effects in adult atopic dermatitis patients were injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, and cold sores in the mouth or on the lips.8

CRSwNP can reduce or eliminate a person’s sense of smell. In a one-year clinical trial of Dupixent with standard of care compared to standard of care alone in adults with CRSwNP, patients on Dupixent improved their sense of smell by 71%, versus a 6% worsening in the standard of care group.30,31

In addition, 67% of the total improvement in sense of smell was measured at two weeks after the first dose.30,31 In two clinical trials, at 24 weeks, Dupixent reduced nasal congestion by as much as 50% (vs. 17% with standard of care) and significantly reduced nasal polyp size compared to standard of care.8 The most common side effects in CRSwNP patients included injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, high count of a certain white blood cell (eosinophilia), trouble sleeping (insomnia), toothache, gastritis and joint pain (arthralgia).8

Results on itch and loss of smell seen as early as week 2 in the trials suggested that type 2 inflammation may reach farther than thought.32,33,34

“These results really opened our eyes to the idea that inflammatory signals can regulate some symptoms directly,” Hamilton says. “We are still learning how type 2 inflammation may be connected to sensory nerve cell control of symptoms like itch and smell.”

Researchers also observed rapid efficacy of Dupixent in helping people with asthma breathe better, also known as lung function. In a one-year clinical trial of Dupixent with standard of care compared to standard of care alone, patients 12 years and older with specific types of moderate-to-severe asthma experienced improved lung function within two weeks, with up to 72% of the total improvement seen after the first dose.8 At 12 weeks, patients on Dupixent with standard of care significantly improved their lung function as compared to standard of care alone and this was sustained through 52 weeks.8 Importantly, Dupixent reduced asthma attacks by up to 67% over one year in these patients compared to standard of care alone.8 The most common side effects in asthma patients included injection site reactions, pain in the throat (oropharyngeal pain), and high count of a certain white blood cell (eosinophilia).8

IMPORTANT SAFETY INFORMATION

Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you:

  • have eye problems
  • have a parasitic (helminth) infection
  • are scheduled to receive any vaccinations. You should not receive a “live vaccine” if you are treated with DUPIXENT.
  • are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.
    • There is a pregnancy exposure registry for women who take DUPIXENT during pregnancy to collect information about the health of you and your baby. Your healthcare provider can enroll you or you may enroll yourself. To get more information about the registry call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/.
  • are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk.

Please scroll down or click here to view full Important Safety Information and Indications

Illustration of two scientists

A rare opportunity

By targeting two components of the immune system that contribute to the type 2 inflammation that underlies certain diseases, Dupixent represents another approach to treatment. It shows that by identifying an underlying cause of disease, we can develop effective medications. We can also discover aspects of these diseases that were never appreciated before, for example, by exploring how biological processes such as type 2 inflammation manifest themselves in the body.35

“Not only are we breaking barriers in treatment as the first biologic medicine to treat uncontrolled moderate-to-severe atopic dermatitis and CRSwNP, but we also have the opportunity to really understand a lot of the underlying biology,” Hamilton says.

“That’s a rare opportunity,” Patel adds. He feels exceedingly fortunate to be part of the team that is helping to realize that vision with Dupixent.

“It’s such a privilege for me to work on this clinical program,” he says. “Few times in your career do you get to make a real difference for patients, and at the same time make a meaningful scientific contribution.”

Important Safety Information & Indications


Do not use if you are allergic to dupilumab or to any of the ingredients in DUPIXENT®.

Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you:

  • have eye problems
  • have a parasitic (helminth) infection
  • are scheduled to receive any vaccinations. You should not receive a “live vaccine” if you are treated with DUPIXENT.
  • are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.
    • There is a pregnancy exposure registry for women who take DUPIXENT during pregnancy to collect information about the health of you and your baby. Your healthcare provider can enroll you or you may enroll yourself. To get more information about the registry call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/.
  • are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Especially tell your healthcare provider if you are taking oral, topical, or inhaled corticosteroid medicines; have asthma and use an asthma medicine; or have atopic dermatitis or CRSwNP, and also have asthma. Do not change or stop your corticosteroid medicine or other asthma medicine without talking to your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine or other asthma medicine to come back.

DUPIXENT can cause serious side effects, including:

  • Allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following symptoms: breathing problems, fever, general ill feeling, swollen lymph nodes, swelling of the face, mouth and tongue, hives, itching, fainting, dizziness, feeling lightheaded (low blood pressure), joint pain, or skin rash.
  • Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision.
  • Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive DUPIXENT. This may happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known whether this is caused by DUPIXENT. Tell your healthcare provider right away if you have: rash, shortness of breath, persistent fever, chest pain, or a feeling of pins and needles or numbness of your arms or legs.

The most common side effects include:

  • Atopic dermatitis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, and cold sores in your mouth or on your lips.
  • Asthma: injection site reactions, pain in the throat (oropharyngeal pain), and high count of a certain white blood cell (eosinophilia).
  • Chronic rhinosinusitis with nasal polyposis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, high count of a certain white blood cell (eosinophilia), trouble sleeping (insomnia), toothache, gastritis, and joint pain (arthralgia).

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch, or call 1-800-FDA-1088.

Use DUPIXENT exactly as prescribed. Your healthcare provider will tell you how much DUPIXENT to inject and how often to inject it. DUPIXENT is an injection given under the skin (subcutaneous injection). If your healthcare provider decides that you or a caregiver can give DUPIXENT injections, you or your caregiver should receive training on the right way to prepare and inject DUPIXENT. Do not try to inject DUPIXENT until you have been shown the right way by your healthcare provider. In children 12 years of age and older, it is recommended that DUPIXENT be administered by or under supervision of an adult. In children younger than 12 years of age, DUPIXENT should be given by a caregiver.

Please see accompanying full Prescribing Information including Patient Information.

INDICATIONS

DUPIXENT is a prescription medicine used:

  • to treat people aged 6 years and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 years of age.
  • with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in people aged 12 years and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 12 years of age.
  • with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.

DUP.20.08.0206 01/21

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