Sanofi: FDA Approves Asthma Indication for Dupixent® (Dupilumab)

FDA Approves Asthma Indication For Dupixent^® (Dupilumab)

• Only approved biologics for moderate and severe asthmatic patients with eosinophilic phenotype
• Only biological product approved for oral asthma dependent on corticosteroids, no matter the phenotype
• Only biological product for asthma allowing patients to self-administer at home
• Only organic products for asthma are also approved for adult patients with moderate to severe atopic dermatitis, an inflammatory type 2 disease induced by the IL-4 and IL pathways. -13.
• In clinical trials, Dupixent reduced severe exacerbations and the use of oral corticosteroids, while improving lung function.

PARIS and TARRYTOWN, NY – October 19, 2018 – The US Food and Drug Administration has approved Dupixent^® (dupilumab) as add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with eosinophilic phenotype or oral corticosteroid-dependent asthma.

Dupixent inhibits the overactive signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that contribute to type 2 inflammation that may be at the origin of moderate to severe asthma. This effect is associated with the reduction of inflammatory biomarkers, including fractionated exhaled nitric oxide (FeNO), immunoglobulin E (IgE) and eotaxin-3 (CCL26).

"Dupixent is now approved in the United States for two major groups of uncontrolled asthmatic patients – those moderate to severe with eosinophilic phenotype or those with oral corticosteroid-dependent asthma," said George D. Yancopoulos, MD, Ph.D., President and Scientific Director of Regeneron. "In the asthma clinical trial program, Dupixent reduced severe exacerbations and use of oral corticosteroids, improved quality of life, and showed statistically and clinically significant improvements in lung function." regarding atopic dermatitis and asthma, and recently announced positive Phase 3 results in chronic rhinosinusitis with nasal polyps, we are committed to advancing our extensive program for the development of additional type 2 inflammatory diseases. "

"Today's approval marks a significant development for some people with moderate to severe asthma aged 12 and older. For oral corticosteroid-dependent patients, Dupixent improved lung function, reduced the use of oral corticosteroids, and reduced exacerbations, regardless of the initial eosinophil levels. " Olivier Brandicourt, MD, General Manager, Sanofi. "Despite the wide range of asthma treatments, so many patients with moderate-to-severe asthma still have unmet needs." Because Dupixent works differently than other biologics, there is now a new option. treatment for some of these patients, Dupixent has already made the difference for many adults with atopic dermatitis, and we now have the opportunity to do the same for some adults and adolescents with moderate-to-severe asthma in the United States. United "

Patients with moderate to severe asthma often have persistent, uncontrolled symptoms despite standard treatment that may make them suitable for treatment with biologic therapy. They live with coughing, wheezing, difficulty breathing and risk of severe asthma attacks that may require emergency visits or hospitalizations.^[1],^[2] Oral corticosteroids can relieve severe symptoms in the short term. However, their chronic use is limited to the most serious patients because of the risk of serious side effects.^[3],^[4]

"While they are complying with their current treatment, many people with moderate to severe asthma, including those with an eosinophilic phenotype or oral steroid dependence, are living with persistent symptoms such as seizures. unpredictable and breathing difficulties, "said Kenneth Mendez, president and CEO of the American Foundation Against Asthma and Allergies (AAFA). "AAFA supports the availability of new and innovative treatment options for asthmatics with uncontrolled symptoms that affect their quality of life."

Dupixent is intended for people with asthma in two doses (200 mg and 300 mg) administered every two weeks at different injection sites after a first loading dose.

Results of the effectiveness and safety of the pivotal clinical trial program

The pivotal trial program evaluated 2,888 adult and adolescent patients with moderate-to-severe asthma in three randomized, placebo-controlled, multicenter trials (Trial 1, Trial 2, and Trial 3). 39, lasting from six months to one year (24 to 52 weeks). All trials included patients, regardless of the initial minimal eosinophil levels.

In Trial 2 (the most important test), Dupixent reduced exacerbations and improved lung function in the general population. Exacerbating benefits were observed in patients with eosinophil counts greater than or equal to 150 cells / microliter, which accounted for 70% of patients included. The effectiveness has improved in patients with high numbers of eosinophils. For example, in patients with blood eosinophils of 300 cells / microliter or greater, Dupixent reduced severe exacerbations by 67% compared with placebo and improved FEV1.₁ (pulmonary function) from 29% to 33%, versus 14% to 16% for placebo. In patients whose eosinophil count was less than 150 cells / microliter, there was no difference between the rates of severe exacerbation between Dupixent and placebo.

In Trial 3, which tested patients with severe oral corticosteroids, Dupixent reduced the average daily use of oral corticosteroids by 70% compared to 42% with placebo. More than half of patients treated with Dupixent have completely eliminated the use of oral corticosteroids. The effects on lung function and on the reduction of oral steroids and oral exacerbation were similar in Dupixent, regardless of baseline eosinophil levels.

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

Additional data can be found in the prescription information. The data from Trial 1 have been published in The lancet April 2016 and the data from trials 2 and 3 were published in the New England Journal of Medicine in May 2018.

About Dupixent

Dupixent is presented in a pre-filled syringe. It is intended for subcutaneous injection (subcutaneous injection) under the supervision of a health care provider. It can be administered in a clinic or, for convenience, at home by self-administration after training by a health professional.

Dupixent is also approved in the United States for the treatment of adults with moderate to severe atopic dermatitis whose disease is not adequately controlled by prescribed topical treatments or where such treatments are not recommended. In the United States, Dupixent is marketed by Sanofi Genzyme, Sanofi's global specialty care division, and Regeneron.

The wholesale purchase cost of Dupixent remains unchanged and will be the same for both doses of asthma. Sanofi and Regeneron are committed to helping patients in the United States who are prescribed Dupixent to have access to the drug and to receive the support they may need. DUPIXENT MyWay^®program. For more information, call 1-844-DUPIXENT (1-844-387-4936) or visit www.DUPIXENT.com.

Dupixent is currently undergoing a regulatory study on moderate to severe asthma in several other countries, including Japan and the European Union (EU).

Dupilumab's development program is underway

Sanofi and Regeneron are also studying dupilumab as part of a broad range of clinical development programs for diseases caused by type 2 inflammation, including chronic rhinosinusitis with nasal polyps (phase 3), asthma of the child (phase 3), atopic dermatitis of the child (phase 3), atopic dermatitis (phase 3), eosinophilic esophagitis (phase 3), allergy to the grass (phase 2) ) and allergy to peanut (phase 2). A future trial is planned for chronic obstructive pulmonary disease. Dupixent is also being studied in combination with REGN-3500, which targets IL-33. These potential uses are experimental and the safety and efficacy have not been evaluated by any regulatory authority. Dupilumab and REGN-3500 are jointly developed by Sanofi and Regeneron as part of a global collaborative agreement.

For more information on clinical trials of dupilumab, please visit www.clinicaltrials.gov.

IMPORTANT INFORMATION ON SAFETY AND INDICATIONS FOR US PATIENTS
Do not use if you are allergic to dupilumab or any of the ingredients of DUPIXENT®.

Before using DUPIXENT, inform your health care provider of all your medical conditions, including if you:

• have eye problems (if you also have atopic dermatitis)
• have a parasitic infection (helminths)
• take oral, topical or inhaled corticosteroids. Do not stop taking your corticosteroid medications unless directed otherwise by your health care provider. This may result in the return of other symptoms controlled by the corticosteroid medication.
• are intended to receive vaccines. You should not receive a "live vaccine" if you are treated with DUPIXENT.
• Are pregnant or planning to become pregnant It is not known if DUPIXENT will harm your unborn baby.
• breastfeed or plan to breastfeed. It is not known if DUPIXENT passes into breast milk.

Inform your health care provider of any medications you are taking, including prescription and over-the-counter medications, vitamins, and herbal supplements. If you are taking medication for asthma, do not modify and stop taking your asthma medications without consulting your health care provider.

DUPIXENT can cause serious side effects, comprising:

• Allergic reactions (hypersensitivity), including a serious reaction called anaphylaxis. Stop using DUPIXENT and talk to your health care provider or get emergency help if you experience any of the following symptoms: breathing problems, fever, feeling of general malaise, swollen lymph nodes, swelling of the face, mouth and tongue, hives, itching, fainting, dizziness, lightheadedness (low blood pressure), joint pain or rash.
• Eye problems. If you have atopic dermatitis, talk to your health care provider if you have new or worsening vision problems, including eye pain or vision impairment.
• Inflammation in your blood vessels: Rarely, this can happen in people with asthma receiving DUPIXENT. This usually, but not always, occurs in people who are also taking an oral steroid drug, who is stopped or whose dose is reduced. Inform your health care provider immediately if you have: skin rash, shortness of breath, persistent fever, chest pain, pins and needles, or numbness of arms or legs .

The most common side effects include injection site reaction, throat pain (oropharyngeal pain) and cold sores in the mouth or on the lips. Inflammation of the eyes and eyelids, including redness, swelling and itching, has been observed in patients with atopic dermatitis.

Tell your health care provider if you have a side effect that bothers you or does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice on side effects. We encourage you to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Use DUPIXENT exactly as prescribed. If your health care provider decides that you or a caregiver can give DUPIXENT injections, you or your caregiver should be trained on how to prepare and inject DUPIXENT. Do not try injecting DUPIXENT until your health care provider shows you the right way. In adolescents with asthma aged 12 years and older, it is recommended to:
DUPIXENT be administered by or under the supervision of an adult.

Please see the complete prescribing information enclosed, including patient information.

INDICATIONS

DUPIXENT is a prescription medication used:

• to treat adults with moderate to severe atopic dermatitis (eczema) who are not well controlled with prescription treatments used on the skin (topical), or who can not use topical treatments. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children under 18 years of age with atopic dermatitis.
• with other asthma medications for the treatment of maintenance of moderate to severe asthma in people aged 12 and over whose asthma is not not controlled with their current medications for asthma. DUPIXENT helps prevent severe asthma attacks (exacerbations) and may improve your breathing. DUPIXENT can 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.

About Regeneron

Regeneron (NASDAQ: REGN) is a leading biotech company that invents life-transforming drugs for people with serious diseases. Founded and led for 30 years by medical scientists, our unique ability to translate science repeatedly and consistently into medicine has led to seven FDA-approved treatments and many product candidates in development, all developed in our labs. Our drugs and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancers, cardiovascular and metabolic diseases, neuromuscular diseases, infectious diseases and rare diseases.

Regeneron speeds up and enhances the development process of traditional medicines with our patented system VelociSuite^® technologies, such as VelocImmune^® which produces all-human optimal antibodies and ambitious research initiatives such as the Regeneron Genetics Center, which is leading one of the world's largest sequencing efforts.

For more information on the company, go to www.regeneron.com or follow @regeneron on Twitter.

About Sanofi Sanofi is committed to helping people meet their health challenges. We are a global biopharmaceutical company focused on human health. We prevent diseases through vaccines, provide innovative treatments to fight pain and relieve suffering. We support the rare people with rare diseases and the millions of people with chronic diseases in the long term. With more than 100,000 people in 100 countries, Sanofi turns scientific innovation into healthcare solutions around the world. Sanofi, empowering life
Sanofi Press Relations Contact Ashleigh Koss Tel: +1 908-981-8745 [email protected] Regeneron Media Relations Sarah Cornhill Tel: +1 914-847-5018 [email protected]	Investor Relations Contact Sanofi George Grofik Tel: +33 (0) 1 53 77 45 45 [email protected] Regeneron Investor Relations Manisha Narasimhan, Ph.D. Tel: +1 914-847-5126 [email protected]
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^[1] Global Asthma Initiative (GINA). Global Strategy for Asthma Management and Prevention. 2018. Available at: http://ginasthma.org/download/832/. Last accessed in July 2018.

^[2] Price D, Fletcher M, T. van der Molen. Control and management of asthma in 8,000 European patients: REALIZE survey on the recognition of asthma and the link between symptoms and experience. NPJ Prim Care Respir Med 2014; 24: 14009.

^[3] Daugherty J et al. The impact of long-term systemic use of glucocorticoids in severe asthma: a retrospective cohort analysis in the United Kingdom. J Asthma. September 19, 2017: 1-8.

^[4] Lefebvre et al. Burden of systemic complications related to glucocorticoids in severe asthma. Curr Med Res Opin. 2017 Jan; 33 (1): 57-65.