TARRYTOWN, N.Y. and
PARIS, Feb.
25, 2019 /PRNewswire/ --
Dupixent showed significant improvement on every primary and
secondary endpoint in patients with severe CRSwNP who had failed
previous treatment with surgery and/or systemic
corticosteroids
Dupixent also showed significant improvement of co-morbid
asthma
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi
today announced detailed results from two Phase 3 trials in adults
with recurring severe chronic rhinosinusitis with nasal polyps
(CRSwNP) despite previous treatment with surgery and/or systemic
corticosteroids. These trials, known as SINUS-24 and SINUS-52,
demonstrated that Dupixent® (dupilumab), when added to
the standard-of-care corticosteroid nasal spray, improved nasal
polyp size, nasal congestion severity, chronic sinus disease, sense
of smell and co-morbid asthma outcomes. In these severe patients,
Dupixent reduced the need for systemic corticosteroid use and the
need for nasal/sinus surgery. These data were presented in two
late-breaking sessions at the 2019 Annual Meeting of the American
Academy of Allergy, Asthma & Immunology (AAAAI) in San Francisco.
"Dupixent is the first biologic therapy to demonstrate the
potential to produce disease-modifying effects in severe CRSwNP,
significantly improving all disease measures in the study,
including sense of smell, one of the most troublesome and
challenging-to-treat symptoms for patients," said Claus Bachert, M.D., Professor and Head of
Clinics of the Department of Otorhinolaryngology at Ghent University and principal investigator of
the trials. "Patients with co-morbid CRSwNP and asthma are often
more difficult to treat so it is encouraging that Dupixent, which
targets key drivers of Type 2 inflammation, may address both
conditions in these patients."
Dupixent is a human monoclonal antibody specifically designed to
inhibit signaling of interleukin-4 and interleukin-13 (IL-4 and
IL-13). The findings from these trials, as well as from prior
trials in atopic dermatitis and asthma, demonstrate that these are
two key proteins that play a central role in Type 2 inflammation,
which seems to underlie CRSwNP as well as several other allergic
diseases.
CRSwNP is a chronic disease of the upper airway predominantly
driven by Type 2 inflammation and characterized by polyps that
obstruct the sinuses and nasal passages. Current treatment options
are intranasal corticosteroids, systemic corticosteroids and
surgery, all with suboptimal efficacy and/or high recurrence rates
after treatment. Patients may experience severe nasal
obstruction with breathing difficulties, nasal discharge, reduced
or loss of sense of smell and taste and facial pain or
pressure.
Persistent symptoms of CRSwNP have a substantial adverse impact
on patients' health-related quality of life, a composite that
includes reduced productivity and activities of daily living,
inability to enjoy food, lack of sleep and fatigue.
The 24-week SINUS-24 and 52-week SINUS-52 trials evaluated
Dupixent 300 mg every two weeks with standard-of-care mometasone
furoate nasal spray (MFNS) ("Dupixent group") compared to placebo
injection plus MFNS ("placebo group"). SINUS-52 also included a
third patient group who switched from Dupixent every two weeks to
Dupixent every four weeks after the primary endpoint was assessed
at week 24.
The topline results for both trials were announced in
October 2018. These trials met their
co-primary endpoints of change from baseline in nasal
congestion/obstruction severity and change from baseline in nasal
polyps score, measured at 24 weeks. Patients treated with Dupixent
experienced a:
- 57% and 51% improvement in their nasal congestion/obstruction
severity compared to a 19% and 15% improvement with placebo in
SINUS-24 and SINUS-52, respectively (absolute change from baseline
of -1.34 and -1.25 for Dupixent compared to -0.45 and -0.38 for
placebo; p<0.0001 for both)
- 33% and 27% reduction in their nasal polyps score compared to a
7% and 4% increase for placebo in SINUS-24 and SINUS-52,
respectively (absolute change from baseline of -1.89 and -1.71 for
Dupixent compared to 0.17 and 0.10 for placebo; p<0.0001 for
both)
New Data Presented at AAAAI
Dupixent significantly
reduced chronic sinus disease in both trials. Dupixent treatment
effects began as early as four weeks with progressive improvement
up to 24 weeks in SINUS-24, a 24-week trial, and up to 52 weeks in
SINUS-52. Both trials evaluated Dupixent treatment every two weeks
for up to 24 weeks, and after week 24 through 52 weeks, SINUS-52
included a group of patients treated every four weeks in addition
to a group treated every two weeks.
Patients in the Dupixent every two weeks group experienced
a:
- 42% and 27% improvement in sinus opacification vs. 4% and 0%
with placebo at 24 weeks in SINUS-24 and SINUS-52, respectively
(absolute change from baseline of -8.18 and -5.21 for Dupixent vs.
-0.74 and -0.09 for placebo; p<0.0001 for both). At 52 weeks in
SINUS-52, a 37% improvement in sinus opacification was achieved
with Dupixent treatment vs. 2% with placebo (absolute change from
baseline of -6.83 for Dupixent vs. 0.11 for placebo; nominal
p<0.0001)
- 146% and 108% improvement in ability to identify different
smells vs. 19% and 7% with placebo at 24 weeks in SINUS-24 and
SINUS-52, respectively (absolute change from baseline of 11.26 and
9.71 for Dupixent vs. 0.7 and -0.81 for placebo; p<0.0001 for
both). In both trials, Dupixent-treated patients reported an
improvement in sense of smell as early as four weeks based on a
separate daily assessment
- 60% and 51% improvement in health-related quality of life vs.
18% and 18% with placebo at 24 weeks in SINUS-24 and SINUS-52,
respectively (absolute change from baseline of -30.43 and -27.77
for Dupixent vs. -9.31 and -10.4 for placebo; p<0.0001 for
both). At 52 weeks in SINUS-52, there was a 58% improvement in
health-related quality of life with Dupixent vs. 14% with placebo
(absolute change from baseline of -29.84 for Dupixent vs. -8.88;
p<0.0001)
- 0.21L improvement in lung function vs. placebo at 24 weeks in
SINUS-24 in the subset of patients with asthma at baseline
(absolute change from baseline of 0.15L for Dupixent vs. -0.06L for
placebo; nominal p=0.0004) and 0.21L improvement in lung function
vs. placebo at 24 weeks in SINUS-52 (absolute change from baseline
of 0.17L for Dupixent vs. -0.015L for placebo; nominal
p<0.0001). In the trials, approximately 60% of patients had
co-morbid asthma, most of them receiving asthma controller
medication
- 73% reduction in rescue treatment with systemic corticosteroids
or nasal polyp surgery compared with placebo at 24 weeks in
SINUS-24 and 76% reduction in rescue treatment compared with
placebo at 52 weeks in SINUS-52 (Kaplan-Meier estimates at 24 weeks
were 7% for Dupixent vs. 23% for placebo in SINUS-24, HR 0.27 [95%
CI: 0.13 to 0.55], nominal p=0.0003; and Kaplan-Meier estimates at
52 weeks were 13% for Dupixent vs. 44% for placebo in SINUS-52, HR
0.24 [0.16 to 0.36]; nominal p<0.0001)
Overall, rates of adverse events were generally similar between
the Dupixent-treated group and placebo. Treatment-emergent adverse
events occurred less frequently in the Dupixent group compared to
placebo (65% vs. 71% in SINUS-24; 83% vs. 91% in SINUS-52). Adverse
events that were observed more frequently in the Dupixent group
compared with placebo included epistaxis (nosebleeds) in SINUS-24
(8% vs. 3%) and bronchitis (6% vs. 5%), cough (6% vs. 5%) and
injection site reactions (3% vs. 2%) in SINUS-52. The rate of
serious adverse events was 4% with Dupixent vs. 14% with placebo in
SINUS-24, and 5% with Dupixent vs. 10% with placebo in SINUS-52.
Adverse events leading to discontinuation occurred in 4% with
Dupixent vs. 2% with placebo in SINUS-24 and 4% with Dupixent vs.
11% with placebo in SINUS-52.
Other Dupixent presentations at AAAAI included analyses on
allergic rhinitis, CRSwNP and other sino-nasal outcomes in patients
with co-morbid asthma or atopic dermatitis.
In the U.S., Dupixent is approved for treatment of adult
patients with moderate-to-severe atopic dermatitis that is not well
controlled by topical prescription therapies, or who cannot use
topical therapies; Dupixent is also approved in the U.S. for use
with other asthma medicines for maintenance treatment of
moderate-to-severe asthma in people aged 12 years and older with an
eosinophilic phenotype or with oral corticosteroid dependent
asthma. Other potential uses for Dupixent are investigational and
the safety and efficacy have not been evaluated by the U.S. Food
and Drug Administration, the European Medicines Agency or any other
regulatory authority. Dupilumab is being developed jointly by
Regeneron and Sanofi as part of a global collaboration
agreement.
About the SINUS-24 and SINUS-52 Trials
SINUS-24
(n=276) and SINUS-52 (n=448) were randomized double-blind,
placebo-controlled pivotal Phase 3 trials in patients with severe
CRSwNP. SINUS-24 included two treatment groups added to nasal
spray: 300 mg Dupixent every two weeks for 24 weeks or placebo
every two weeks for 24 weeks. SINUS-52 included three treatment
groups added to nasal spray: 300 mg Dupixent every two weeks for 52
weeks, 300 mg Dupixent every two weeks for 24 weeks and then every
four weeks until 52 weeks, or placebo every two weeks for 52 weeks.
The co-primary and secondary endpoints of the trials included
change from baseline in: nasal congestion/obstruction severity, a
0-3 scale, at 24 weeks (co-primary); nasal polyps score (a measure
of polyp size), as assessed by nasal endoscopy, a 0-8 scale, at 24
weeks (co-primary); Lund-Mackay
score, a 0-24 scale, as assessed by computed tomography (CT) scans
at 24 weeks; University of Pennsylvania
Smell Identification Test (UPSIT), 0-40 scale, at 24 weeks;
severity of decreased or loss of smell by patient daily assessment
on a 0-3 scale at 24 weeks; 22-item Sino-Nasal Outcome Test
(SNOT-22), a 0-110 scale at 24 weeks; and the previous endpoints up
to 52 weeks in SINUS-52.
Other pre-specified endpoints included the: change from baseline
to 24 weeks in forced expiratory volume over one second
(FEV1) in patients with co-morbid asthma; and proportion
of patients during trial treatment who received rescue treatment
with systemic corticosteroids and/or nasal polyp surgery.
The trials enrolled patients who were 18 years or older with
bilateral nasal polyps who, despite treatment with systemic
corticosteroids in the previous two years or history of surgery,
continued to have ongoing moderate or severe symptoms of nasal
congestion, blockage, loss of smell or nasal discharge. Consistent
with the overlap seen among patients with Type 2 or allergic
inflammatory diseases, more than three-quarters also suffered from
other conditions, including asthma (approximately 59%), allergic
rhinitis (approximately 58%) and NSAID-exacerbated respiratory
disease (approximately 28%). Patients with co-morbid asthma and
CRSwNP tend to have more severe disease.
Dupilumab Development Program
In addition to the
approved indications in moderate-to-severe atopic dermatitis and
moderate-to-severe asthma, Regeneron and Sanofi are also studying
dupilumab in a broad range of clinical development programs for
diseases driven by allergic and other Type 2 inflammation,
including pediatric (6 to 11 years of age) atopic dermatitis (Phase
3), pediatric (6 months to 5 years of age) atopic dermatitis (Phase
2/3), adolescent (12 to 17 years of age) atopic dermatitis (Phase 3
completed), pediatric (6 to 11 years of age) asthma (Phase 3),
eosinophilic esophagitis (Phase 2/3) and food and environment
allergies (Phase 2). A future trial is planned for chronic
obstructive pulmonary disease. Dupilumab is also being studied in
combination with REGN3500, which targets IL-33. These potential
uses are investigational and the safety and efficacy have not been
evaluated by any regulatory authority. Dupilumab and REGN3500 were
invented using Regeneron's proprietary
VelocImmune® technology that yields optimized
fully human antibodies.
For more information on dupilumab clinical trials please visit
www.clinicaltrials.gov.
U.S. INDICATIONS
DUPIXENT is a prescription medicine used:
- to treat adults 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 18 years of age.
- with other asthma medicines for the maintenance treatment of
moderate-to-severe 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.
IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS
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 (if you also have atopic dermatitis)
- have a parasitic (helminth) infection
- are taking oral, topical, or inhaled corticosteroid medicines.
Do not stop taking your corticosteroid medicines unless
instructed by your healthcare provider. This may cause other
symptoms that were controlled by the corticosteroid medicine to
come back.
- 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.
- 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. If you are taking asthma medicines, do not
change or stop your asthma medicine without talking to your
healthcare provider.
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. If you have atopic dermatitis, tell your
healthcare provider if you have any new or worsening eye problems,
including eye pain or changes in vision.
- Inflammation in 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 injection site reactions, pain in the
throat (oropharyngeal pain) and cold sores in your mouth or on your
lips. Eye and eyelid inflammation, including redness,
swelling and itching have been seen in patients who have atopic
dermatitis.
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 www.fda.gov/medwatch, or call 1-800-FDA-1088.
Use DUPIXENT exactly as prescribed. 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 adolescents with asthma 12 years of age and
older, it is recommended that DUPIXENT be administered by or under
supervision of an adult.
Please see accompanying full Prescribing Information
including Patient Information.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading
biotechnology company that invents life-transforming medicines for
people with serious diseases. Founded and led for 30 years by
physician-scientists, our unique ability to repeatedly and
consistently translate science into medicine has led to seven
FDA-approved treatments and numerous product candidates in
development, all 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, neuromuscular diseases,
infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune® which produces optimized fully-human
antibodies, and ambitious research initiatives such as the
Regeneron Genetics Center, which is conducting one of the largest
genetics sequencing efforts in the world.
For additional information about the company, please visit
www.regeneron.com or follow @Regeneron on Twitter.
About Sanofi
Sanofi is dedicated to supporting people
through their health challenges. We are a global biopharmaceutical
company focused on human health. We prevent illness with vaccines,
provide innovative treatments to fight pain and ease suffering. We
stand by the few who suffer from rare diseases and the millions
with long-term chronic conditions.
With more than 100,000 people in 100 countries, Sanofi is
transforming scientific innovation into healthcare solutions around
the globe.
Sanofi, Empowering Life
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
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without limitation Dupixent® (dupilumab) Injection; the
likelihood, timing, and scope of possible regulatory approval and
commercial launch of Regeneron's late-stage product candidates and
new indications for marketed products, such as dupilumab for the
treatment of chronic rhinosinusitis with nasal polyps, pediatric
atopic dermatitis, pediatric asthma, eosinophilic esophagitis,
grass allergy, food allergy (including peanut), chronic obstructive
pulmonary disease, and other potential indications (as well as in
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and product candidates (such as Dupixent) and the impact of studies
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changes to the assumptions underlying those projections or
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including Regeneron's agreements with Sanofi, Bayer, and Teva
Pharmaceutical Industries Ltd. (or their respective affiliated
companies, as applicable), to be cancelled or terminated without
any further product success; and risks associated with intellectual
property of other parties and pending or future litigation relating
thereto, including without limitation the patent litigation
proceedings relating to EYLEA® (aflibercept) Injection,
Dupixent, and Praluent® (alirocumab) Injection, the
ultimate outcome of any such litigation proceedings, and the impact
any of the foregoing may have on Regeneron's business, prospects,
operating results, and financial condition. A more complete
description of these and other material risks can be found in
Regeneron's filings with the U.S. Securities and Exchange
Commission, including its Form 10-K for the year ended December 31, 2018. Any forward-looking
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Regeneron uses its media and investor relations website and
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Forward-looking statements are generally identified by the words
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Regeneron
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