Confirming the results of Study A, this second pivotal trial in biologic-naïve patients met primary and key secondary endpoints, showing treatment with Dupixent resulted in a nearly 50% reduction in itch and urticaria activity scores compared to placebo

More than 300,000 people in the U.S. suffer from CSU that is inadequately controlled by antihistamines

Data will support regulatory resubmission in the U.S. by year-end; if approved, Dupixent would be the first targeted therapy for CSU in a decade

TARRYTOWN, N.Y. and PARIS, Sept.  11, 2024  (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that a Dupixent (dupilumab) confirmatory Phase 3 trial (LIBERTY-CUPID Study C) met the primary and key secondary endpoints for the investigational treatment of patients with uncontrolled, biologic-naïve chronic spontaneous urticaria (CSU) receiving background therapy with antihistamines. CSU is a chronic skin condition that causes sudden and debilitating hives and persistent itch, which can impact quality of life. This positive trial confirms results from Study A, the first Phase 3 trial of Dupixent in this setting. Earlier this year, Japan was the first country in the world to approve and launch Dupixent for adult and adolescent CSU patients based on the results from Study A.

"Patients with uncontrolled chronic spontaneous urticaria experience debilitating itch and hives that appear without warning and disrupt their lives," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. "With a nearly 50% reduction in itch and urticaria activity scores compared to placebo, these positive Phase 3 results reaffirm the potential of Dupixent to bring relief and its well-established safety profile to those living with this chronic inflammatory skin disease."

Study C enrolled 151 children and adults who were randomized to receive Dupixent (n=74) or placebo (n=77) added to standard-of-care histamine-1 (H1) antihistamines. At 24 weeks, efficacy among patients receiving Dupixent compared to placebo was as follows:

• 8.64-point reduction in itch severity from baseline with Dupixent versus a 6.10-point reduction with placebo (p=0.02).

• 15.86-point reduction in urticaria activity (itch and hive) severity from baseline with Dupixent versus an 11.21-point reduction with placebo (p=0.02).

Notably, 30% of Dupixent-treated patients reported no urticaria (complete response) compared to 18% of those on placebo (p=0.02).

The safety results were generally consistent with the known safety profile of Dupixent in its approved dermatological indications. Overall rates of treatment emergent adverse events (AEs) were 53% for Dupixent and 53% for placebo. AEs more commonly observed with Dupixent (≥5%) compared to placebo included injection site reactions (12% vs. 4%), accidental overdose (7% vs. 3%) and COVID-19 infection (8% vs. 5%).

Detailed results from this trial will be provided to the U.S. Food and Drug Administration by year-end 2024 in response to the additional data requested for inclusion in the supplemental biologics license application for Dupixent in CSU. These data are also planned for presentation at a forthcoming medical meeting.

"The positive pivotal data from this study reinforce the potential of Dupixent to offer a new treatment option for the many people suffering from chronic spontaneous urticaria who do not respond to standard-of-care antihistamines," said Dietmar Berger, M.D., Ph.D., Chief Medical Officer, Global Head of Development at Sanofi. "With clinically meaningful reductions in itch and hives for patients receiving Dupixent, we look forward to sharing these data with the FDA to bring Dupixent to patients with CSU in the U.S. as soon as possible. With Dupixent now treating 1 million patients across seven approved indications, these new results underscore there are still many more patients that Dupixent can potentially benefit."

Outside of Japan, the safety and efficacy of Dupixent for CSU has not been fully evaluated by any regulatory authority.

About Chronic Spontaneous Urticaria (CSU)
CSU is a chronic inflammatory skin disease driven in part by type 2 inflammation, which causes sudden and debilitating hives and persistent itch. CSU is typically treated with H1 antihistamines, medicines that target H1 receptors on cells to control symptoms of urticaria. However, the disease remains uncontrolled despite antihistamine treatment in many patients, some of whom are left with limited alternative treatment options. These individuals continue to experience symptoms that can be debilitating and significantly impact their quality of life.

About the Dupixent Phase 3 CSU Program (LIBERTY-CUPID)
The LIBERTY-CUPID Phase 3 program evaluating Dupixent in CSU consists of Study A, Study B and Study C. Study C was a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of Dupixent as an add-on to standard-of-care antihistamines compared to antihistamines alone in 151 patients aged six years and older with CSU who remained symptomatic despite antihistamine use and were not previously treated with omalizumab (i.e., biologic-naïve). The primary endpoint assessed the change from baseline in itch at 24 weeks (measured by the weekly itch severity score [ISS7], 0-21 scale). A key secondary endpoint was the change from baseline in itch and hives at 24 weeks (measured by the weekly urticaria activity score [UAS7], 0-42 scale).

Study A supported the approval of Dupixent in Japan for the treatment of CSU in people aged 12 years and older whose disease is not adequately controlled with existing therapy.

Results from Study A and Study B (which assessed Dupixent in patients aged 12 years and older who were uncontrolled on standard-of-care H1 antihistamines and refractory to omalizumab) were published in the Journal of Allergy and Clinical Immunology.

About Dupixent
Dupixent, which was invented using Regeneron's proprietary VelocImmune technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases.

Dupixent has received regulatory approvals in more than 60 countries in one or more indications including certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, prurigo nodularis, CSU, and chronic obstructive pulmonary disease in different age populations. More than 1,000,000 patients are being treated with Dupixent globally.

About Regeneron's VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV (casirivimab and imdevimab), Dupixent, Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb), Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz (pozelimab-bbfg).

Dupilumab Development Program
Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.

In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including chronic pruritus of unknown origin and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.

U.S. INDICATIONS
DUPIXENT is a prescription medicine used:

• to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) 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 months of age.

• with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age 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 6 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.

• to treat adults and children 1 year of age and older with eosinophilic esophagitis (EoE), who weigh at least 33 pounds (15 kg). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 1 year of age, or who weigh less than 33 pounds (15 kg).

• to treat adults with prurigo nodularis (PN). It is not known if DUPIXENT is safe and effective in children with prurigo nodularis 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.

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" right before and during treatment with DUPIXENT.

• are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.

  • A pregnancy registry for women who take DUPIXENT during pregnancy collects information about the health of you and your baby. To enroll or get more information call 1-877-311-8972 or go to .

• 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, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, or prurigo nodularis 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. DUPIXENT can cause allergic reactions that can sometimes be severe. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms: breathing problems or wheezing, swelling of the face, lips, mouth, tongue or throat, fainting, dizziness, feeling lightheaded, fast pulse, fever, hives, joint pain, general ill feeling, itching, skin rash, swollen lymph nodes, nausea or vomiting, or cramps in your stomach-area.

• Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision, such as blurred vision. Your healthcare provider may send you to an ophthalmologist for an exam if needed.

• 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, chest pain, worsening shortness of breath, a feeling of pins and needles or numbness of your arms or legs, or persistent fever.

• Joint aches and pain. Some people who use DUPIXENT have had trouble walking or moving due to their joint symptoms, and in some cases needed to be hospitalized. Tell your healthcare provider about any new or worsening joint symptoms. Your healthcare provider may stop DUPIXENT if you develop joint symptoms.

The most common side effects include:

• Eczema: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, dry eye, cold sores in your mouth or on your lips, and high count of a certain white blood cell (eosinophilia).

• Asthma: injection site reactions, high count of a certain white blood cell (eosinophilia), pain in the throat (oropharyngeal pain), and parasitic (helminth) infections.

• Chronic Rhinosinusitis with Nasal Polyposis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, high count of a certain white blood cell (eosinophilia), gastritis, joint pain (arthralgia), trouble sleeping (insomnia), and toothache.

• Eosinophilic Esophagitis: injection site reactions, upper respiratory tract infections, cold sores in your mouth or on your lips, and joint pain (arthralgia).

• Prurigo Nodularis: eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, herpes virus infections, common cold symptoms (nasopharyngitis), dizziness, muscle pain, and diarrhea.

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 , or call 1-800-FDA-1088.

Use DUPIXENT exactly as prescribed by your healthcare provider. It's an injection given under the skin (subcutaneous injection). Your healthcare provider will decide if you or your caregiver can inject DUPIXENT. Do not try to prepare and inject DUPIXENT until you or your caregiver have been trained by your healthcare provider. In children 12 years of age and older, it's recommended DUPIXENT be administered by or under supervision of an adult. In children 6 months to less than 12 years of age, DUPIXENT should be given by a caregiver.

Please see accompanying full Prescribing Information including Patient Information.

About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.

For more information, please visit  or follow Regeneron on LinkedIn, Instagram, Facebook or X.

About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.

Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY.

Regeneron Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products") and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation Dupixent (dupilumab); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, such as Dupixent for the treatment of chronic spontaneous urticaria ("CSU") as discussed in this press release as well as other potential indications; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products (such as Dupixent for the treatment of CSU) and Regeneron's Product Candidates; whether the results from the confirmatory Phase 3 trial discussed in this press release will be sufficient for purposes of the request from the U.S. Food and Drug Administration for additional data to include in the supplemental biologics application for Dupixent in CSU; the ability of Regeneron's collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products (such as Dupixent) and Regeneron's Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable) to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics (such as the COVID-19 pandemic) on Regeneron's business; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA (aflibercept) Injection), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. 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Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website () and its LinkedIn page ().

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