TARRYTOWN, N.Y. and
PARIS, April 27, 2020 /PRNewswire/ --
Independent Data Monitoring Committee recommended continuing
ongoing Phase 3 trial only in the more advanced "critical" group
with Kevzara higher-dose versus placebo
and discontinuing less advanced "severe" group
Phase 3 trial will be amended to enroll only "critical"
patients
Phase 3 trial also be amended to discontinue lower-dose
Kevzara (200 mg); all new patients to receive either higher-dose
Kevzara (400 mg) or placebo
No new safety findings were observed for Kevzara use in
COVID-19 patients
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and
Sanofi today announced the preliminary results from the Phase 2
portion of an ongoing Phase 2/3 trial evaluating
Kevzara® (sarilumab), an interleukin-6 (IL-6) receptor
antibody, in hospitalized patients with "severe" or "critical"
respiratory illness caused by COVID-19. Following a review by the
Independent Data Monitoring Committee (IDMC) of all available Phase
2 and Phase 3 data, the trial will be immediately amended so that
only "critical" patients continue to be enrolled to receive Kevzara
400 mg or placebo.
The randomized Phase 2 portion of the trial compared
intravenously-administered Kevzara higher dose (400 mg), Kevzara
lower dose (200 mg) and placebo. It assessed 457 hospitalized
patients, who were categorized at baseline as having either
"severe" illness (28% of patients), "critical" illness (49% of
patients) or "multi-system organ dysfunction" (MSOD) (23% of
patients). Patients were classified as "severe" if they required
oxygen supplementation without mechanical or high-flow oxygenation;
or "critical" if they required mechanical ventilation or high-flow
oxygenation or required treatment in an intensive care unit.
Preliminary analysis of the Phase 2 portion of the trial
demonstrated that Kevzara rapidly lowered C-reactive protein (CRP),
a key marker of inflammation, meeting the primary endpoint (see
table below). Baseline levels of IL-6 were elevated across all
treatment arms, with higher levels observed in "critical" patients
compared to "severe" patients. Additionally, no new safety signals
were observed with the use of Kevzara in COVID-19 patients.
Analysis of clinical outcomes in the Phase 2 trial was
exploratory and pre-specified to focus on the "severe" and
"critical" groups. In the preliminary Phase 2 analysis, Kevzara had
no notable benefit on clinical outcomes when combining the "severe"
and "critical" groups, versus placebo. However, there were negative
trends for most outcomes in the "severe" group, while there were
positive trends for all outcomes in the "critical" group (see table
below). Subsequent to the IDMC review, Regeneron and Sanofi
reviewed the discontinued "severe" group data, which revealed that
the negative trends in the Phase 2 trial (n=126) were not
reproduced in Phase 3 trial (n=276), and that clinical outcomes
were balanced across the Kevzara and placebo treatment arms.
Outcomes for the "severe" group were better than expected based on
prior reports, regardless of treatment assignment: for example, in
the Phase 2 portion, approximately 80% were discharged, 10% of
patients died and 10% remain hospitalized.
"Even in a pandemic setting, it's both crucial and possible to
obtain controlled data in adequately-sized trials to provide the
evidence needed to inform optimal medical care," said George D. Yancopoulos, M.D., Ph.D., Regeneron
Co-Founder, President and Chief Scientific Officer. "Emerging
evidence with Kevzara and other repurposed drugs in the COVID-19
crisis highlight the challenges of making decisions about existing
medicines for new viral threats using small, uncontrolled studies.
We await results of the ongoing Phase 3 trial to learn more about
COVID-19, and better understand whether some patients may benefit
from Kevzara treatment. In addition, there is an acute need
for tailored approaches that specifically target this virus. To
that end, Regeneron is rapidly advancing our targeted
anti-SARS-CoV-2 antibody cocktail and we plan to initiate clinical
trials in June."
The Kevzara trial was designed after a small (n=21), single-arm
study in China (Xu et al)
among mostly severe, febrile hospitalized COVID-19 patients found
elevated IL-6 levels and suggested that inhibiting this pathway
with the IL-6 blocker tocilizumab rapidly reduced fever and
improved oxygenation in severe patients, allowing for successful
hospital discharge. These uncontrolled findings require
confirmation in adequately-sized and well-controlled trials. Last
month, Regeneron and Sanofi moved rapidly to evaluate Kevzara in a
prospective, randomized, placebo-controlled adaptively-designed
U.S. Phase 2/3 trial in collaboration with U.S. groups including
the Biomedical Advanced Research and Development Authority (BARDA,
part of the office of the Assistant Secretary for Preparedness and
Response at the U.S. Department of Health and Human Services), the
Food and Drug Administration (FDA) and hospitals across the
country.
"At Sanofi, we are committed to help combat the global COVID-19
pandemic. As we quickly follow the science to better understand
this disease and explore how to best treat patients, these initial
results from the randomized clinical trial setting provide
physicians much needed insights and information regarding the
potential of Kevzara for patients with COVID-19 treatment," said
John Reed, M.D., Ph.D., Sanofi's
Global Head of Research and Development. "While our evaluation of
the use of Kevzara for COVID-19 treatment remains an
investigational approach, Sanofi continues to stay at the forefront
of multiple initiatives to fight this disease, including
researching other potential treatment options, developing vaccine
candidates that can be manufactured at large-scale, and a potential
collaboration for an innovative SARS-CoV-2 smartphone-based
self-testing solution."
The Phase 2 numerical results are presented in the table below,
including exploratory clinical endpoints for the "critical" group,
which is the focus of the ongoing Phase 3 trial.
U.S. Kevzara Trial – Phase 2 Efficacy
Results
|
Placebo
|
Kevzara 200
mg
|
Kevzara 400
mg
|
PRIMARY ENDPOINT
(REDUCTION IN C-REACTIVE PROTEIN)
|
|
(n=77)
|
(n=136)
|
(n=145)
|
% change from
baseline in CRP
(Patients with high
baseline IL-6, where data was
available)
|
-21%
|
-77%
|
-79%
|
EXPLORATORY CLINICAL
ENDPOINTS IN "CRITICAL" GROUP
|
|
(n=44)
|
(n=94)
|
(n=88)
|
Died or "On a
ventilator"
|
24 (55%)
|
43 (46%)
|
28 (32%)
|
Died
|
12
(27%)
|
34
(36%)
|
20
(23%)
|
On a
ventilator
|
12
(27%)
|
9
(10%)
|
8
(9%)
|
Clinical
improvement
(Achieved ³2 point
improvement on 7-point scale)1
|
18 (41%)
|
48 (51%)
|
52 (59%)
|
Off
oxygenation
|
18 (41%)
|
40 (43%)
|
51 (58%)
|
Discharged
|
18 (41%)
|
37 (39%)
|
47 (53%)
|
1. 7-point scale consists of: 1) death; 2)
hospitalized, requiring invasive mechanical ventilation or
extracorporeal membrane oxygenation (ECMO); 3) hospitalized,
requiring non-invasive ventilation or high flow oxygen devices; 4)
hospitalized, requiring supplemental oxygen; 5) hospitalized, not
requiring supplemental oxygen – requiring ongoing medical care
(COVID-19 related or otherwise); 6) hospitalized, not requiring
supplemental oxygen – no longer requires ongoing medical care; 7)
discharged from hospital.
The ongoing portion of the Phase 3 trial, which is continuing to
enroll, currently includes more than 600 patients in the "critical"
group. Regeneron and Sanofi remain blinded to the ongoing portion
of the Phase 3 trial and expect to report results by June.
In addition, the companies are also conducting a second trial in
countries outside of the U.S. The Phase 3 trial of Kevzara in
approximately 400 patients hospitalized with COVID-19 infection is
currently enrolling in Italy,
Spain, Germany, France, Canada, Russia, Israel and Japan. Initial results from this second trial
are expected in the third quarter of 2020. The findings from the
U.S. trial will be shared immediately with the IDMC and similar
amendments to the trial outside the U.S. will be considered.
The U.S. Kevzara trial has been funded in part with Federal
funds from the Department of Health and Human Services; Office of
the Assistant Secretary for Preparedness and Response; and BARDA,
under OT number: HHSO100201700020C.
The use of Kevzara to treat the symptoms of COVID-19 is
investigational and has not been fully evaluated by any regulatory
authority.
Kevzara was jointly developed by Regeneron and Sanofi under a
global collaboration agreement. Kevzara is a fully-human monoclonal
antibody that was invented using Regeneron's proprietary
VelocImmune® technology that utilizes a
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 Dupixent®
(dupilumab), Praluent® (alirocumab) and
Libtayo® (cemiplimab), which are approved in multiple
countries around the world. Regeneron previously used its
VelociSuite® technologies to rapidly develop an
investigational treatment for Ebola virus infection (currently
under review by the FDA) and is now using these same technologies
to create novel preventative and therapeutic antibodies for
COVID-19.
About Kevzara® (sarilumab)
Injection
Kevzara is currently approved in multiple
countries to treat adults with moderately to severely active
rheumatoid arthritis who have not responded to or tolerated
previous therapy.
Kevzara binds specifically to the IL-6 receptor and has been
shown to inhibit IL-6-mediated signaling. IL-6 is an immune system
protein produced in increased quantities in patients with
rheumatoid arthritis and has been associated with disease activity,
joint destruction and other systemic problems. Kevzara is being
investigated for its ability to reduce the overactive inflammatory
immune response associated with COVID-19 based on evidence of
markedly elevated levels of IL-6 in severely ill patients infected
with coronaviruses.
IMPORTANT SAFETY INFORMATION FOR KEVZARA®
(sarilumab) INJECTION
KEVZARA can cause serious side effects including:
- SERIOUS INFECTIONS: KEVZARA is a medicine that
affects your immune system. KEVZARA can lower the ability of your
immune system to fight infections. Some people have serious
infections while using KEVZARA, including tuberculosis (TB), and
infections caused by bacteria, fungi, or viruses that can spread
throughout the body. Some people have died from these
infections. Your healthcare provider should test you for TB
before starting KEVZARA. Your healthcare provider should monitor
you closely for signs and symptoms of TB during treatment with
KEVZARA.
- Before starting KEVZARA, tell your healthcare provider if
you:
-
- think you have an infection or have symptoms of an infection,
with or without a fever. Symptoms may include sweats or chills,
muscle aches, a cough, shortness of breath, blood in your phlegm,
weight loss, warm, red, or painful skin or sores on your body,
diarrhea or stomach pain, burning when you urinate or urinating
more often than normal, if you feel very tired, or if you are being
treated for an infection, get a lot of infections or have repeated
infections
- have diabetes, HIV, or a weakened immune system
- have TB, or have been in close contact with someone with
TB
- live or have lived, or have traveled to certain parts of the
country (such as the Ohio and
Mississippi River valleys and the Southwest) where there is an
increased chance of getting certain fungal infections
(histoplasmosis, coccidioidomycosis, or blastomycosis)
- have or have had hepatitis
- After starting KEVZARA, call your healthcare provider right
away if you have any symptoms of an infection.
- CHANGES IN CERTAIN LABORATORY TEST RESULTS: Your
healthcare provider should do blood tests before and after starting
KEVZARA to check for low neutrophil (white blood cells that help
the body fight off bacterial infections) counts, low platelet
(blood cells that help with blood clotting and stop bleeding)
counts, and an increase in certain liver function tests. Changes in
test results are common with KEVZARA and can be severe. You may
also have changes in other laboratory tests, such as your blood
cholesterol levels. Your healthcare provider should do blood tests
4 to 8 weeks after starting KEVZARA and then every 6 months during
treatment to check for an increase in blood cholesterol
levels.
- TEARS (PERFORATION) OF THE STOMACH OR INTESTINES: Tell
your healthcare provider if you have had a condition known as
diverticulitis (inflammation in parts of the large intestine) or
ulcers in your stomach or intestines. Some people using KEVZARA had
tears in their stomach or intestine. This happens most often in
people who also take nonsteroidal anti-inflammatory drugs (NSAIDS),
corticosteroids, or methotrexate. Call your healthcare provider
right away if you have fever and stomach (abdominal) pain that does
not go away.
- CANCER: KEVZARA may increase your risk of certain
cancers by changing the way your immune system works. Tell your
healthcare provider if you have ever had any type of cancer.
- SERIOUS ALLERGIC REACTIONS: Serious allergic reactions
can happen with KEVZARA. Get medical attention right away if you
have any of the following signs: shortness of breath or trouble
breathing; feeling dizzy or faint; swelling of your lips, tongue or
face; moderate or severe stomach (abdominal) pain or vomiting; or
chest pain.
- Do not use KEVZARA if you are allergic to Sarilumab or any of
the ingredients of KEVZARA.
- Before using KEVZARA, tell your healthcare provider if you
-
- have an infection
- have liver problems
- have had stomach (abdominal) pain or a condition known as
diverticulitis (inflammation in parts of the large intestine) or
ulcers in your stomach or intestines
- recently received or are scheduled to receive a vaccine. People
who take KEVZARA should not receive live vaccines
- plan to have surgery or a medical procedure
- are pregnant or plan to become pregnant. It is not known if
KEVZARA will harm your unborn baby
- are breastfeeding or plan to breastfeed. Talk to your
healthcare provider about the best way to feed your baby if you use
KEVZARA. It is not known if KEVZARA passes into your breast
milk
- take any prescription or nonprescription medicines, vitamins or
herbal supplements. It is especially important to tell your
healthcare provider if you use any other medicines to treat your
RA. Using KEVZARA with these medicines may increase your risk of
infection
- medicines that affect the way certain liver enzymes work. Ask
your healthcare provider if you are not sure if your medicine is
one of these
- The most common side effects include:
-
- injection site redness
- upper respiratory tract infection
- urinary tract infection
- nasal congestion, sore throat, and runny nose
These are not all the possible side effects of
KEVZARA. Tell your doctor about any side effect that
bothers you or does not go away. You are encouraged to report side
effects of prescription drugs to the FDA at
www.fda.gov/medwatch or call 1-800-FDA-1088.
WHAT IS KEVZARA?
Kevzara is an injectable prescription medicine called an
interleukin-6 (IL-6) receptor blocker. Kevzara is used to treat
adult patients with moderately to severely active rheumatoid
arthritis (RA) after at least one other medicine called a
disease-modifying antirheumatic drug (DMARD) has been used and did
not work well or could not be tolerated.
Click here for full Prescribing Information including risk
of SERIOUS SIDE EFFECTS and Medication Guide for KEVZARA.
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 over 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, 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.regneron.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 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 impact of
SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on
Regeneron's business and its employees, collaborators, suppliers,
and other third parties on which Regeneron relies, Regeneron's and
its collaborators' ability to continue to conduct research and
clinical programs (including those discussed in this press
release), Regeneron's ability to manage its supply chain, net
product sales of products marketed by Regeneron and/or its
collaborators (collectively, "Regeneron's Products"), and the
global economy; the nature, timing, and possible success and
therapeutic applications of Regeneron's Products and product
candidates and research and clinical programs now underway or
planned, including without limitation Kevzara®
(sarilumab) for the treatment of hospitalized patients with severe
or critical respiratory illness caused by COVID-19 and Regeneron's
novel antibody cocktail for the prevention and treatment of
COVID-19 (the "COVID-19 Multi-antibody Therapy"); 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 Kevzara for the treatment of patients
with COVID-19 and the COVID-19 Multi-antibody Therapy; unforeseen
safety issues resulting from the administration of Regeneron's
Products and product candidates (such as Kevzara and the COVID-19
Multi-antibody Therapy) in patients, including serious
complications or side effects in connection with the use of
Regeneron's Products and 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
product candidates, including without limitation Kevzara and the
COVID-19 Multi-antibody Therapy; ongoing regulatory obligations and
oversight impacting Regeneron's Products (such as Kevzara),
research and clinical programs, and business, including those
relating to patient privacy; uncertainty of market acceptance and
commercial success of Regeneron's Products and product candidates
and the impact of studies (whether conducted by Regeneron or others
and whether mandated or voluntary) on the commercial success of
Regeneron's Products and product candidates; 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 Regeneron's Products and
product candidates; the extent to which the results from the
research and development programs conducted by Regeneron or its
collaborators may be replicated in other studies and lead to
therapeutic applications; the ability of Regeneron to manufacture
and manage supply chains for multiple products and product
candidates; the ability of Regeneron's collaborators, suppliers, or
other third parties (as applicable) to perform manufacturing,
filling, finishing, packaging, labelling, distribution, and other
steps related to Regeneron's Products and product candidates;
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 or collaboration agreement, 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 and other related proceedings
relating to Dupixent® (dupilumab) and
Praluent® (alirocumab)), other litigation and other
proceedings and government investigations relating to the Company
and/or its operations, 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. 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, 2019.
Any forward-looking statements are made based on management's
current beliefs and judgment, and the reader is cautioned not to
rely on any forward-looking statements made by Regeneron.
Regeneron does not undertake any obligation to update publicly any
forward-looking statement, including without limitation any
financial projection or guidance, whether as a result of new
information, future events, or otherwise.
Regeneron uses its media and investor relations website and
social media outlets to publish important information about the
Company, including information that may be deemed material to
investors. Financial and other information about Regeneron is
routinely posted and is accessible on Regeneron's media and
investor relations website (http://newsroom.regeneron.com) and its
Twitter feed (http://twitter.com/regeneron).
Sanofi Forward-Looking Statements
This press
release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical
facts. These statements include projections and estimates and their
underlying assumptions, statements regarding plans, objectives,
intentions and expectations with respect to future financial
results, events, operations, services, product development and
potential, and statements regarding future performance.
Forward-looking statements are generally identified by the words
"expects", "anticipates", "believes", "intends", "estimates",
"plans" and similar expressions. Although Sanofi's management
believes that the expectations reflected in such forward-looking
statements are reasonable, investors are cautioned that
forward-looking information and statements are subject to various
risks and uncertainties, many of which are difficult to predict and
generally beyond the control of Sanofi, that could cause actual
results and developments to differ materially from those expressed
in, or implied or projected by, the forward-looking information and
statements. These risks and uncertainties include among other
things, the uncertainties inherent in research and development,
future clinical data and analysis, including post marketing,
decisions by regulatory authorities, such as the FDA or the EMA,
regarding whether and when to approve any drug, device or
biological application that may be filed for any such product
candidates as well as their decisions regarding labelling and other
matters that could affect the availability or commercial potential
of such product candidates, the fact that product candidates if
approved may not be commercially successful, the future approval
and commercial success of therapeutic alternatives, Sanofi's
ability to benefit from external growth opportunities, to complete
related transactions and/or obtain regulatory clearances, risks
associated with intellectual property and any related pending or
future litigation and the ultimate outcome of such
litigation, trends in exchange rates and prevailing interest
rates, volatile economic and market conditions, cost
containment initiatives and subsequent changes thereto, and
the impact that COVID-19 will have on us, our customers, suppliers,
vendors, and other business partners, and the financial condition
of any one of them, as well as on our employees and on the global
economy as a whole. Any material effect of COVID-19 on any of the
foregoing could also adversely impact us. This situation is
changing rapidly and additional impacts may arise of which we are
not currently aware and may exacerbate other previously identified
risks. The risks and uncertainties also include the uncertainties
discussed or identified in the public filings with the SEC and the
AMF made by Sanofi, including those listed under "Risk Factors" and
"Cautionary Statement Regarding Forward-Looking Statements" in
Sanofi's annual report on Form 20-F for the year ended December 31, 2019. Other than as required by
applicable law, Sanofi does not undertake any obligation to update
or revise any forward-looking information or
statements.
Regeneron
Contacts:
|
Sanofi
Contacts:
|
|
|
Media
Relations
Sarah
Cornhill
Tel: +1 (914)
847-5018
sarah.cornhill@regeneron.com
Investor
Relations
Vesna
Tosic
Tel: +1 (914)
847-5443
Vesna.Tosic@regeneron.com
|
Media
Relations
Ashleigh
Koss
Tel: +1 (908)
981-8745
ashleigh.koss@sanofi.com
Investor
Relations
Felix
Lauscher
Tel.: +33 (0)1 53 77
45 45
ir@sanofi.com
|
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SOURCE Regeneron Pharmaceuticals, Inc.