TARRYTOWN, N.Y. and
PARIS, Oct.
26, 2020 /PRNewswire/ --
First Phase 3 trial in eosinophilic esophagitis (EoE) to show
a biologic medicine significantly improved structural and
histologic measures, while rapidly improving ability to swallow in
patients 12 years and older
New late-breaking data show additional improvements in
disease severity and extent, as well as normalized gene expression
associated with type 2 inflammation
Results presented for the first time at virtual ACG 2020 and
UEG Week 2020
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today
announced additional positive results from Part A of a pivotal
Phase 3 trial evaluating the investigational use of
Dupixent® (dupilumab) in patients 12 years and
older with eosinophilic esophagitis (EoE). As previously reported,
the trial met both of its co-primary and all key secondary
endpoints. New late-breaking data showing additional improvements
in disease severity and extent at the microscopic level, as well as
normalization of gene expression pattern associated with type 2
inflammation, were presented at the virtual American College of
Gastroenterology (ACG) Annual Scientific Meeting and the United
European Gastroenterology (UEG) Week Virtual 2020.
There are currently no FDA-approved medicines for EoE, a chronic
and progressive inflammatory disease that damages the esophagus and
prevents it from working properly. Over time, excessive type 2
inflammation may cause scarring and narrowing of the esophagus,
making it difficult to swallow. EoE can affect a patient's ability
to eat and cause food to become stuck after being swallowed (food
impaction), which can lead to a medical emergency.
Previously announced results showed Dupixent improved
symptomatic, structural and histologic measures of EoE. The use of
Dupixent to treat EoE is investigational and has not been fully
evaluated by any regulatory authority.
"The results from this trial show dupilumab significantly
improved both patients' ability to swallow, as well as structural
abnormalities in the esophagus, by targeting type 2 inflammation to
help reverse tissue damage and scarring that usually worsens over
time," said Evan S. Dellon, M.D.,
M.P.H., Professor of Gastroenterology and Hepatology at the
University of North Carolina School of
Medicine and principal investigator of the trial. "These results
also demonstrate that eosinophilic esophagitis is a disease caused
by factors beyond just the presence of elevated eosinophils.
Dupilumab, which targets the activity of the cytokines IL-4 and
IL-13 that drive type 2 inflammation, was able to show significant
improvements in a broad range of clinical, anatomic, cellular and
molecular measures."
Part A of the randomized, double-blind, placebo-controlled trial
enrolled 81 patients aged 12 years and older with EoE, who were
treated with Dupixent 300 mg weekly over a 24-week treatment period
or placebo.
New results presented at virtual ACG 2020 and UEG Week 2020
showed patients treated with Dupixent experienced:
- Rapid improvement in ability and comfort of swallowing:
patients reported significant improvement on the Dysphagia Symptom
Questionnaire (DSQ) as early as 4 weeks and continued to improve
through 24 weeks (p<0.05 and p<0.001, respectively).
- Reduced esophageal eosinophil count below the diagnostic
disease threshold: 64% of patients treated with Dupixent achieved
<15 eosinophils/high-power field (eos/hpf) compared to 8% for
placebo at 24 weeks (p<0.001). Peak esophageal eosinophil count
was reduced by 71% with Dupixent compared to 3% with placebo from
baseline (p<0.001).
- Reduced severity and extent of the disease at the microscopic
level: the grade and stage scores that measure esophageal tissue
changes associated with the disease were reduced by 0.761 and 0.753
with Dupixent compared to a 0.001 and 0.012 reduction for placebo
at 24 weeks; the EoE Histology Scoring System (EoE-HSS) grade and
stage scores measure changes in eight cellular and tissue features
on four-point scales, respectively (p<0.001 for all
values).
- Normalized gene expression in esophageal tissue: gene
expression pattern associated with type 2 inflammation and EoE was
reduced by 1.97-fold and 2.66-fold, compared to a 0.32-fold and
0.16-fold reduction with placebo, respectively, as measured by the
Normalized Enrichment Score (NES) at 24 weeks from baseline. The
NES evaluated a panel of genes associated with type 2 inflammation
or EoE (p<0.001 for all values). The changes observed with
Dupixent demonstrate a shift in gene expression pattern from one
that resembles EoE disease to a pattern that resembles healthy
controls.
The trial demonstrated similar safety results to the
well-established safety profile of Dupixent in its approved
indications. For the 24-week treatment period, overall rates of
adverse events were 86% for Dupixent and 82% for
placebo. Adverse events that were more commonly observed with
Dupixent included injection site reactions (n=15 for Dupixent, n=12
for placebo) and upper respiratory tract infections (n=11 for
Dupixent, n=6 for placebo). There was one treatment discontinuation
in the Dupixent group due to joint pain.
In September 2020, the FDA granted
Breakthrough Therapy designation to Dupixent for the treatment of
patients 12 years and older with EoE. Breakthrough Therapy
designation is designed to expedite the development and review of
drugs in the U.S. that target serious or life-threatening
conditions. Drugs qualifying for this designation must show
preliminary clinical evidence that it may demonstrate a substantial
improvement on clinically significant endpoints over available
therapies, or over placebo if there are no available therapies. In
2017, Dupixent was also granted Orphan Drug designation for the
potential treatment of EoE. This is given to investigational
medicines intended for the treatment of rare diseases that affect
fewer than 200,000 people in the U.S. and in which no adequate
medicines have been developed and approved.
Dupixent is a fully-human monoclonal antibody that inhibits the
signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13)
proteins, that was invented using Regeneron's proprietary
VelocImmune® technology. Data from Dupixent
clinical trials have shown that IL-4 and IL-13 are key drivers of
the type 2 inflammation that plays a major role in atopic
dermatitis, asthma, chronic rhinosinusitis with nasal polyposis
(CRSwNP) and EoE.
About the Dupixent Eosinophilic Esophagitis Trial
The
Phase 3, randomized, double-blind, placebo-controlled trial
evaluated the efficacy and safety of Dupixent in adolescents and
adults with EoE. Part A of the trial enrolled 81 patients (42
treated with Dupixent and 39 with placebo) aged 12 years and older
with EoE, as determined by histological and patient-reported
measures. The co-primary endpoints assessed the change from
baseline in the DSQ, a patient-reported measure of difficulty
swallowing, and the proportion of patients achieving peak
esophageal intraepithelial eosinophil count of ≤6 eos/hpf, a
measure of esophageal inflammation, at 24 weeks. Key secondary
endpoints of the trial assessed histopathologic measures of the
severity and extent of tissue scarring in the esophagus, as
measured by the EoE-HSS grade and stage scores, and the
proportion of patients achieving peak esophageal intraepithelial
eosinophil count of <15 eos/hpf at 24 weeks. Other secondary
endpoints of the trial assessed NES for the relative change from
baseline to week 24 in the EoE diagnostic panel and type 2
inflammation transcriptome signatures. In total, 85% of these
patients suffered from at least one concurrent atopic condition
such as allergic rhinitis, food allergy and asthma. Patients
received weekly subcutaneous injections of Dupixent 300 mg or
placebo for the 24-week treatment period.
The EoE trial is ongoing, with additional patients enrolling in
Part B as well as patients continuing in a 28-week extended active
treatment period (Part C) after completing either Part A or Part B.
Part B of the trial is evaluating an additional Dupixent dosing
regimen.
About Dupixent
Dupixent is approved for
adolescents and adults with moderate-to-severe atopic dermatitis,
asthma and/or in adults with CRSwNP in a number of countries around
the world, including the European Union and Japan, as well as the U.S. where Dupixent is
also approved for children with moderate-to-severe atopic
dermatitis. Dupixent is currently approved in more than 60
countries, and more than 190,000 patients have been treated
globally.
Dupixent was invented using Regeneron's
VelocImmune® technology that utilizes a
proprietary genetically-engineered mouse platform endowed with a
genetically-humanized immune system to produce optimized
fully-human antibodies. VelocImmune technology has been used
to create multiple antibodies including Libtayo®
(cemiplimab-rwlc), Praluent® (alirocumab) and
Kevzara® (sarilumab), which are approved in multiple
countries around the world. Regeneron previously used these
technologies to rapidly develop a treatment for Zaire ebolavirus infection, which is
approved by the FDA, and to create a potentially preventative and
therapeutic medicine for COVID-19 that was recently submitted to
the FDA for an Emergency Use Authorization (EUA).
Dupilumab Development Program
To date, dupilumab has
been studied in more than 10,000 patients across 50 clinical trials
in various chronic diseases driven 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, including EoE
(Phase 3), pediatric atopic dermatitis (6 months to 5 years of age,
Phase 3), pediatric asthma (6 to 11 years of age, Phase 3), chronic
obstructive pulmonary disease (Phase 3), bullous pemphigoid (Phase
3), prurigo nodularis (Phase 3), chronic spontaneous urticaria
(Phase 3), and food and environmental allergies (Phase 2). These
potential uses are investigational, and the safety and efficacy of
dupilumab in these conditions have not been fully evaluated by any
regulatory authority. Dupilumab is being jointly developed by
Regeneron and Sanofi under a global collaboration agreement.
U.S. 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.
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
- 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 by
indication are as follows:
- 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
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 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 over 30 years by
physician-scientists, our unique ability to repeatedly and
consistently translate science into medicine has led to eight
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, pain, infectious diseases
and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune, which uses unique genetically-humanized mice to
produce optimized fully-human antibodies and bispecific antibodies,
and through 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 statements. Words such as
"anticipate," "expect," "intend," "plan," "believe," "seek,"
"estimate," variations of such words, and similar expressions are
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and environmental allergies, and other potential indications;
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(including without limitation the patent litigation and other
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Injection, Dupixent, and Praluent® (alirocumab)),
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ultimate outcome of any such proceedings and investigations, and
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