PARIS and TARRYTOWN, N.Y., May
21, 2018 /PRNewswire/ -- The New England Journal of
Medicine (NEJM) today published detailed results from two Phase
3 trials for the investigational use of Dupixent®
(dupilumab) in moderate-to-severe asthma. The results showed that
Dupixent significantly reduced the risk of severe asthma attacks
(exacerbations), improved lung function and reduced dependence on
oral corticosteroids (OCS). The trials, known as QUEST and VENTURE,
are part of the pivotal clinical trial program that evaluated
Dupixent in uncontrolled asthma patients. These data were
simultaneously presented at the American Thoracic Society 2018
International Conference.
Dupixent demonstrated significant improvements in the key
primary and secondary endpoints across the overall populations in
both QUEST and VENTURE, with the largest benefit experienced in
patients with more severe Type 2 inflammatory asthma, as evidenced
by elevated blood eosinophils or exhaled nitric oxide levels. Type
2 asthma can also be characterized by other parameters, including
elevated Immunoglobulin E (IgE). Dupixent blocks the IL-4/IL-13
pathway, which is emerging as a central driver of Type 2 allergic
inflammation in asthma, as well as in a range of other allergic or
atopic diseases.
The investigational use of Dupixent as an add-on maintenance
treatment of adults and adolescents with uncontrolled
moderate-to-severe asthma is currently under regulatory review in
several countries, including the U.S., Japan and in the European Union (EU), and the
safety and efficacy for this use have not been evaluated by any
regulatory authority. In the U.S., the target action date is
October 20, 2018. Dupixent is
currently approved in a number of countries for the treatment of
adults with uncontrolled moderate-to-severe atopic dermatitis.
About LIBERTY ASTHMA QUEST
The Phase 3 QUEST trial showed that a broad population of adults
and adolescents with moderate-to-severe asthma (no minimum blood
eosinophil level requirement or other biomarker requirement at
baseline) benefited when Dupixent was added to their standard
therapies. Dupixent reduced severe asthma attacks and
improved lung function compared to placebo. Lung function
improvements were observed from the first measurement two weeks
after receiving the first dose of Dupixent, and improvements were
sustained throughout the 52-week trial. Patients also reported
improved asthma control and quality of life, as measured by the
5-item Asthma Control Questionnaire (ACQ-5) and Asthma Quality of
Life Questionnaire (AQLQ).
"About 20 percent of people
with asthma continue to have uncontrolled moderate-to-severe
symptoms despite available treatments," said Mario Castro, M.D., Alan A. and Edith L. Wolff
Professor of Pulmonary and Critical Care Medicine at Washington University School of Medicine in
St. Louis. "The results published
today in the New England Journal of Medicine show evidence from a
Phase 3 trial that a biologic may have the potential to help a
broad population of patients improve multiple key asthma treatment
goals when added to standard treatments. Dupixent was designed to
inhibit signaling from two important proteins (IL-4 and IL-13)
involved in Type 2 inflammation that contribute to uncontrolled
symptoms in many people with moderate-to-severe asthma."
The QUEST trial enrolled 1,902 patients worldwide including
1,795 adults and 107 adolescents. The four study groups included
patients treated with 200 mg every other week (loading dose of 400
mg), 300 mg every other week (loading dose of 600 mg) and two
separate placebo groups. All patients continued on a medium- or
high-dose inhaled corticosteroid (ICS) and up to two additional
controller medicines throughout the study.
The NEJM publication provides data on key endpoints, including
data in the table below.
QUEST Data
Summary
|
Placebo-adjusted
reduction in annualized rate of severe asthma exacerbations over 52
weeks
|
|
200 mg Dupixent
(n=631) vs.
Placebo (n=317)
|
300 mg Dupixent
(n=633) vs.
Placebo (n=321)
|
Overall
population1
|
48
percent*
|
46
percent*
|
|
200 mg Dupixent
(n=264) vs.
Placebo (n=148)
|
300 mg Dupixent
(n=277) vs.
Placebo (n=142)
|
Patients with 300
eosinophils/microliter or greater
|
66
percent±*
|
67
percent*
|
Placebo-adjusted
absolute (percent) change in lung function (measured by
FEV1) from baseline to week
122
|
|
200 mg Dupixent
(n=611) vs.
Placebo (n=307)
|
300 mg Dupixent
(n=610) vs.
Placebo (n=313)
|
Overall
population1
|
140 mL*
(9
percent)
|
130 mL*
(9
percent)
|
|
200 mg Dupixent
(n=256) vs.
Placebo (n=144)
|
300 mg Dupixent
(n=266) vs.
Placebo (n=139)
|
Patients with 300
eosinophils/microliter or greater
|
210mL±
(13
percent)
|
240mL*
(18
percent)
|
1 Co-primary endpoint, * p-value <0.001,
± p-value nominal
2 Number of patients with FEV1 measurement at
week 12
For the 52-week treatment period, the overall rate of adverse
events was similar across treatment groups (81 percent in the
combined Dupixent-treated group and 83 percent in the combined
placebo-treated group). The rate of serious adverse events was 8
percent in the combined Dupixent-treated group and 8 percent in the
combined placebo-treated group. The most frequent adverse events
that occurred more frequently with Dupixent treatment vs. placebo
were injection site reactions (17 percent vs. 8 percent,
respectively),back pain (4 percent, both groups) and eosinophilia
(4 percent vs. 1 percent, respectively).
About LIBERTY ASTHMA VENTURE
The Phase 3 VENTURE trial also did not require minimum biomarker
levels for enrollment. The study showed that adults and
adolescents with severe, steroid-dependent asthma who were treated
with Dupixent, when added to standard therapies, could reduce their
use of OCS medications while improving asthma control compared to
placebo at 24 weeks. With Dupixent, OCS use decreased by 70 percent
in the overall population (vs. 42 percent for placebo), and 80
percent for patients with baseline eosinophil levels 300
cells/microliter or greater (vs. 43 percent for placebo).
Despite reductions in OCS, patients treated with Dupixent reduced
the risk of severe asthma attacks and improved their lung
function.
"Up to 45 percent of people
with severe asthma rely on systemic corticosteroids to control
their symptoms but potential long-term side-effects should be taken
into account according to global asthma treatment guidelines," said
Klaus Rabe, MD, Director of
the Department of Pneumology at LungenClinic Grosshansdorf and
Professor of Medicine at Christian Albrechts University, Kiel,
Germany. "In the Phase 3 VENTURE
trial, a majority of patients treated with Dupixent and standard
therapies significantly reduced their use of oral steroids, and
nearly half of patients completely stopped using oral steroids,
while improving their asthma."
The 24-week VENTURE study enrolled 210 patients (103 in the
Dupixent group and 107 in the placebo group) with severe asthma who
regularly used maintenance OCS in the six months prior to
enrollment in the study. The two study groups were 300 mg Dupixent
every other week (loading dose of 600 mg) and placebo. All patients
continued on a high-dose ICS and up to two additional controller
medicines throughout the study. The prescribed OCS in the study was
prednisone or prednisolone.
The NEJM publication provides data on key endpoints, including
data in the tables below.
VENTURE Data
Summary
|
Reduction in OCS
dose at 24 weeks
|
|
300 mg Dupixent
(n=103)
|
Placebo
(n=107)
|
Overall
population1
|
70
percent*
|
42 percent
|
|
300 mg Dupixent
(n=48)
|
Placebo
(n=41)
|
Patients with 300
eosinophils/microliter or greater
|
80
percent*
|
43 percent
|
Proportion of
patients with 50 percent or greater reduction in OCS
|
Overall
population
|
80
percent*
|
50 percent
|
Proportion of
patients who reduced their OCS dose to less than 5 mg per
day
|
Overall
population
|
69
percent*
|
33 percent
|
1 Primary endpoint, * p-value vs. placebo
<0.001
VENTURE Data
Summary, Continued
|
|
Difference between
300 mg
DUPIXENT (n=103) vs.
Placebo (n=107)
(Overall
population)
|
Difference between
300 mg
DUPIXENT (n=48) vs.
Placebo (n=41)
(Patients with 300
eosinophils/
microliter or greater)
|
Change in
annualized rate of
severe asthma exacerbations
over 24 weeks
|
59 percent
reduction*
|
71 percent
reduction±
|
Absolute (percent)
change in
FEV1 from baseline to 24 weeks
|
220 mL (15
percent***) improvement*
|
320 mL (25
percent***) improvement±
|
* Nominal p-value vs. placebo < 0.001
±Nominal p-value vs. placebo < 0.005
*** Data not included in NEJM publication
For the 24-week treatment period, the overall rate of adverse
events was similar across treatment groups (62 percent in the
Dupixent-treated group and 64.5 percent in the placebo-treated
group). The rate of serious adverse events was 9 percent in the
Dupixent-treated group and 6 percent in the placebo-treated group.
The most frequent adverse events that occurred more frequently with
Dupixent treatment vs. placebo were injection site reaction (9
percent vs. 4 percent, respectively), bronchitis (7 percent vs. 6
percent, respectively), sinusitis (7 percent vs. 4 percent,
respectively) and eosinophilia (14 percent vs. 1 percent,
respectively).
Dupilumab Development
Program
Sanofi and Regeneron are also studying dupilumab in a
broad range of clinical development programs for diseases driven by
Type 2 inflammation, including pediatric atopic dermatitis (Phase
3), nasal polyps (Phase 3) and eosinophilic esophagitis (Phase 2).
Future trials are planned for chronic obstructive
pulmonary disease, grass allergy and food allergy (including
peanut). These potential uses are investigational
and the safety and efficacy have not been evaluated by any
regulatory authority. Dupilumab is being jointly developed by
Sanofi and Regeneron under a global collaboration
agreement.
For more information on dupilumab clinical trials please
visit www.clinicaltrials.gov.
About
Dupixent®
(dupilumab)
Dupixent is currently approved in the U.S.
for the treatment of adults with moderate-to-severe atopic
dermatitis whose disease is not adequately controlled with topical
prescription therapies, or when those therapies are not advisable.
Dupixent is also approved for use in certain patients with
moderate-to-severe atopic dermatitis in the EU and a number of
other countries, including Canada,
and Japan.
IMPORTANT SAFETY INFORMATION AND
INDICATION
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
- have asthma
- 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 have asthma and 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. Stop using
Dupixent and go to the nearest hospital emergency room if you get
any of the following symptoms: fever, general ill feeling, swollen
lymph nodes, hives, itching, 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.
The most common side effects
include injection site reactions, eye and
eyelid inflammation, including redness, swelling and itching, and
cold sores in your mouth or on your lips.
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 may report side effects to the FDA
at 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.
Please
click here for
the full Prescribing Information. The patient information is
available here.
INDICATION
Dupixent is used to treat adult patients 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. Dupixent is
administered by subcutaneous injection at different injection sites
every two weeks after an initial loading dose. Dupixent is intended
for use under the guidance of a healthcare provider. A patient may
self-inject Dupixent after training in subcutaneous injection
technique using the pre-filled syringe.
About Sanofi
Sanofi (EURONEXT: SAN) (NYSE: SNY) 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
About Regeneron Pharmaceuticals,
Inc.
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
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For additional information about the company, please visit
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Sanofi Media
Relations Contact Ashleigh
Koss Tel.: +1
908-981-8745 mr@sanofi.com
Regeneron Media
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+1 914-847-1546 sharon.chen@regeneron.com
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Investor Relations
Contact George Grofik
Tel.: +33 (0)1 53 77 45 45
ir@sanofi.com
Regeneron Investor
Relations Contact Manisha
Narasimhan, Ph.D. Tel: +1
914-847-5126 Manisha.narasimhan@regeneron.com
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