Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
positive data from three independent cohorts evaluating an
investigational combination of LAG-3 inhibitor fianlimab and PD-1
inhibitor Libtayo® (cemiplimab) in adults with advanced
melanoma. The early clinical trial results, which demonstrated the
combination led to clinically meaningful and durable results across
multiple clinical settings, will be shared in an oral session at
the 2023 American Society of Clinical Oncology (ASCO) Annual
Meeting in Chicago on Monday, June 5 at 3:00 PM CT.
“LAG-3 inhibitors are known to complement PD-1 inhibitors in the
treatment of advanced melanoma. There exists an unmet need to
further improve the benefit to patients, including those with liver
metastases and other high-risk prognostic markers,” said Omid
Hamid, M.D., Director, Clinical Research and Immunotherapy at The
Angeles Clinic and Research Institute, and principal investigator
of the trial. “These updated and independent expansion cohort
results reinforce the potential of the fianlimab and cemiplimab
(Libtayo) combination to deliver clinically meaningful and durable
responses in diverse clinical settings and patient populations,
with an acceptable safety profile. Particularly encouraging is that
the clinical activity was observed in post hoc analyses of patient
subgroups, including in patients with a poor prognosis or those who
had been previously treated with an anti-PD-1 therapy in the
adjuvant setting.”
The data to be presented at ASCO 2023 include findings from
three independent expansion cohorts of adults with unresectable or
metastatic melanoma who were all naïve to anti-PD-1 therapy for
advanced disease (n=98). Additional follow up will be reported on
an initial cohort of first- or second-line patients (n=40) and a
confirmatory cohort of first-line patients (n=40), previously
reported at ESMO 2022. New for this presentation is a cohort of
patients who had received prior systemic treatment for melanoma in
the neoadjuvant or adjuvant setting (n=18), including adjuvant
anti-PD-1 therapy (n=13 of 18).
Tumor responses were based on RECIST 1.1 criteria and per
investigator assessment. The median duration of response (DOR) was
not reached in any cohort, and the objective response rate (ORR) by
cohort was as follows:
- Initial cohort: 63% (25 of 40 patients),
including 6 complete responses (CR) and 19 partial responses
(PR).
- Confirmatory cohort: 63% (25 of 40 patients),
including 5 CRs and 20 PRs.
- Prior neo/adjuvant systemic therapy cohort:
56% (10 of 18 patients). Among the 13 patients in this latest
cohort who had prior anti-PD-1 adjuvant
treatment, the ORR was 62% (8 of 13 patients), including 1
CR and 7 PRs.
In a post hoc analysis of the three combined cohorts, the ORR
was 61% (60 of 98 patients), the median progression-free survival
(PFS) was 15 months per Kaplan-Meier estimate (95% CI: 9–NE), and
the median follow-up was 13 months (interquartile range 9-19).
Additional post hoc analyses found clinically meaningful activity
in multiple subgroups of interest, with ORRs in each as
follows:
- Poor prognosis: 53% (17 of 32 patients) in
cases with high baseline lactate dehydrogenase (LDH), 43% (9 of 21
patients) in cases of liver metastasis, and 35% (6 of 17 patients)
in cases of M1c stage (visceral metastatic) disease and high
baseline LDH.
- Varying tumor PD-L1 expression levels: 73% (19
of 26 patients) in cases of ≥1% PD-L1 expression and 56% (23 of 41
patients) in cases of <1% PD-L1 expression.
The safety profile of the fianlimab and Libtayo combination in
these expansion cohorts appeared to be generally consistent with
the safety profile of Libtayo monotherapy and other anti-PD-(L)1
agents, except for higher rates of adrenal insufficiency, which
were ≤Grade 2 in the majority of cases (64%) and all cases were
successfully managed with steroid replacement. Adverse events (AEs)
occurred in 94% of patients, with 44% being ≥Grade 3 and 30%
considered serious. AEs occurring in ≥10% of patients included rash
(20%), pruritis (16%), diarrhea (15%), arthralgia (13%),
hypothyroidism (12%), adrenal insufficiency (11%) and myalgia
(10%). The treatment discontinuation rate due to AEs was 16%.
“Fianlimab in combination with Libtayo has now demonstrated
robust response rates in three independent advanced melanoma
cohorts – each with unique patient populations,” said Israel Lowy,
M.D., Ph.D., Senior Vice President, Translational and Clinical
Sciences, Oncology at Regeneron. “These positive results support
the clinical potential of fianlimab in combination with Libtayo. We
look forward to partnering with the oncology community to further
investigate this combination in a broad pivotal clinical
development program that includes Phase 3 trials in the advanced
and adjuvant melanoma settings, alongside ongoing Phase 2/3 trials
in non-small cell lung cancer and research in other solid
tumors.”
Additional presentations on the fianlimab and Libtayo
combination will be shared at ASCO during a poster session on
Saturday, June 3 from 1:15 to 4:15 PM CT, including:
- A Phase 1 study of fianlimab (anti-LAG-3) in combination with
cemiplimab (anti-PD-1) in patients with advanced melanoma: poor
prognosis subgroup analysis (#9548)
- A Phase 3 trial of fianlimab (anti-LAG-3) plus cemiplimab
(anti-PD-1) versus pembrolizumab in patients with previously
untreated unresectable locally advanced or metastatic melanoma
(#TPS9602)
- A Phase 3 trial comparing fianlimab (anti-LAG-3) plus
cemiplimab (anti-PD-1) to pembrolizumab in patients with completely
resected high-risk melanoma (#TPS9598)
The potential use of fianlimab and Libtayo described above is
investigational, and safety and efficacy of this combination have
not been evaluated by any regulatory authority.
About Regeneron’s Approach to Cancer Research
At Regeneron, we’re applying more than three decades of scientific
innovation with the goal of developing paradigm-changing therapies
for patients with cancer.
Our portfolio is built around two foundational approaches – our
approved PD-1 inhibitor Libtayo and investigational bispecific
antibodies – which are being evaluated both as monotherapies and in
combination with emerging therapeutic modalities. Together, they
provide us with unique combinatorial flexibility to develop
potentially synergistic treatments for a wide range of solid tumors
and blood cancers.
If you are interested in learning more about our clinical
trials, please contact us (clinicaltrials@regeneron.com or
844-734-6643) or visit our clinical trials website.
About the Phase 1 Trial The Phase 1 trial is a
first-in-human, multi-cohort study investigating fianlimab in
combination with Libtayo in patients with advanced melanoma. The
primary endpoint is ORR per RECIST 1.1 criteria; secondary
endpoints include PFS, DOR, disease control rate (DCR), safety and
pharmacokinetics (PK).
In these three expansion cohorts, 98 patients were enrolled and
received fianlimab 1600 mg and Libtayo 350 mg intravenously every 3
weeks for up to 51 weeks, with a median follow up of 12.6 months
and median treatment duration of 32.9 weeks. Additional analyses
from the Phase 1 trial are ongoing.
About fianlimabFianlimab is a fully human
monoclonal antibody targeting the immune checkpoint receptor LAG-3
on T cells and was invented using Regeneron’s proprietary
VelocImmune® technology. In melanoma, LAG-3 expression on
cancer cells is associated with therapeutic resistance to PD-1
inhibitors. Fianlimab is being investigated in combination with
Regeneron's PD-1 inhibitor Libtayo to determine whether concurrent
blockade of LAG-3 and PD-1 can help overcome this resistance and
release the brakes on T cell activation.
About LibtayoLibtayo is a fully human
monoclonal antibody targeting the immune checkpoint receptor PD-1
on T cells and was invented using Regeneron's proprietary
VelocImmune® technology. By binding to PD-1, Libtayo has been shown
to block cancer cells from using the PD-1 pathway to suppress
T-cell activation. In the U.S. and other countries
Libtayo is indicated in certain patients with advanced basal cell
carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC)
and advanced NSCLC, as well as in advanced cervical cancer
in the European Union, Canada and Brazil. As
of July 1, 2022, Libtayo is developed and marketed globally by
Regeneron.
In the U.S., the generic name for Libtayo in its
approved indications is cemiplimab-rwlc, with rwlc as the
suffix designated in accordance with Nonproprietary Naming of
Biological Products Guidance for Industry issued by the U.S.
Food and Drug Administration (FDA). Outside of the U.S.,
the generic name of Libtayo in its approved indication is
cemiplimab.
The extensive clinical program for Libtayo is focused on
difficult-to-treat cancers. Libtayo is currently being investigated
in trials as a monotherapy, as well as in combination with either
conventional or novel therapeutic approaches for other solid tumors
and blood cancers. These potential uses are investigational,
and their safety and efficacy have not been evaluated by any
regulatory authority.
U.S. FDA-approved Indications Libtayo
is a prescription medicine used to treat:
- People with a type of skin cancer called cutaneous squamous
cell carcinoma (CSCC) that has spread or cannot be cured by surgery
or radiation.
- People with a type of skin cancer called basal cell carcinoma
(BCC) when your BCC cannot be removed by surgery (locally advanced
BCC) or when it has spread (metastatic BCC) and have received
treatment with a hedgehog pathway inhibitor (HHI), or cannot
receive treatment with a HHI.
- Adults with a type of lung cancer called non-small cell lung
cancer (NSCLC).
- LIBTAYO may be used in combination with chemotherapy that
contains a platinum medicine as your first treatment when your lung
cancer has not spread outside your chest (locally advanced lung
cancer) and you cannot have surgery or chemotherapy with radiation,
or your lung cancer has spread to other areas of your body
(metastatic lung cancer), and your tumor does not have an abnormal
“EGFR,” “ALK,” or “ROS1” gene.
- LIBTAYO may be used alone as your first treatment when your
lung cancer has not spread outside your chest (locally advanced
lung cancer) and you cannot have surgery or chemotherapy with
radiation, or your lung cancer has spread to other areas of your
body (metastatic lung cancer), and your tumor tests positive for
high “PD-L1,” and your tumor does not have an abnormal “EGFR,”
“ALK,” or “ROS1” gene.
It is not known if Libtayo is safe and effective in
children.
IMPORTANT SAFETY INFORMATION
FOR U.S. PATIENTS
What is the most important information I should know
about LIBTAYO?LIBTAYO is a medicine that may treat certain
cancers by working with your immune system. LIBTAYO can cause your
immune system to attack normal organs and tissues in any area of
your body and can affect the way they work. These problems can
sometimes become severe or life-threatening and can lead to death.
You can have more than one of these problems at the same time.
These problems may happen anytime during treatment or even after
your treatment has ended.Call or see your healthcare
provider right away if you develop any new or worsening signs or
symptoms, including:
- Lung problems: cough, shortness of breath, or
chest pain
- Intestinal problems: diarrhea (loose stools)
or more frequent bowel movements than usual, stools that are black,
tarry, sticky or have blood or mucus, or severe stomach-area
(abdomen) pain or tenderness
- Liver problems: yellowing of your skin or the
whites of your eyes, severe nausea or vomiting, pain on the right
side of your stomach-area (abdomen), dark urine (tea colored), or
bleeding or bruising more easily than normal
- Hormone gland problems: headache that will not
go away or unusual headaches, eye sensitivity to light, eye
problems, rapid heartbeat, increased sweating, extreme tiredness,
weight gain or weight loss, feeling more hungry or thirsty than
usual, urinating more often than usual, hair loss, feeling cold,
constipation, your voice gets deeper, dizziness or fainting, or
changes in mood or behavior, such as decreased sex drive,
irritability, or forgetfulness
- Kidney problems: decrease in
your amount of urine, blood in your urine, swelling of your ankles,
or loss of appetite
- Skin problems: rash, itching, skin blistering
or peeling, painful sores or ulcers in mouth or nose, throat, or
genital area, fever or flu-like symptoms, or swollen lymph
nodes
- Problems can also happen in other organs and tissues.
These are not all of the signs and symptoms of immune system
problems that can happen with LIBTAYO. Call or see your healthcare
provider right away for any new or worsening signs or symptoms,
which may include: chest pain, irregular heartbeat,
shortness of breath or swelling of ankles, confusion, sleepiness,
memory problems, changes in mood or behavior, stiff neck, balance
problems, tingling or numbness of the arms or legs, double vision,
blurry vision, sensitivity to light, eye pain, changes in eyesight,
persistent or severe muscle pain or weakness, muscle cramps, low
red blood cells, or bruising
- Infusion reactions that can sometimes be severe or
life-threatening. Signs and symptoms of infusion reactions
may include: nausea, vomiting, chills or shaking, itching or rash,
flushing, shortness of breath or wheezing, dizziness, feel like
passing out, fever, back or neck pain, or facial swelling
- Rejection of a transplanted organ. Your
healthcare provider should tell you what signs and symptoms you
should report and monitor you, depending on the type of organ
transplant that you have had
- Complications, including graft-versus-host disease
(GVHD), in people who have received a bone marrow (stem cell)
transplant that uses donor stem cells (allogeneic). These
complications can be serious and can lead to death. These
complications may happen if you underwent transplantation either
before or after being treated with LIBTAYO. Your healthcare
provider will monitor you for these complications
Getting medical treatment right away may help keep these
problems from becoming more serious. Your healthcare
provider will check you for these problems during your treatment
with LIBTAYO. Your healthcare provider may treat you with
corticosteroid or hormone replacement medicines. Your healthcare
provider may also need to delay or completely stop treatment with
LIBTAYO if you have severe side effects.
Before you receive LIBTAYO, tell your healthcare
provider about all your medical conditions, including if
you:
- have immune system problems such as Crohn’s disease, ulcerative
colitis, or lupus
- have received an organ transplant
- have received or plan to receive a stem cell transplant that
uses donor stem cells (allogeneic)
- have received radiation treatment to your chest area
- have a condition that affects your nervous system, such as
myasthenia gravis or Guillain-Barré syndrome
- are pregnant or plan to become pregnant. LIBTAYO can harm your
unborn babyFemales who are able to become
pregnant:
- Your healthcare provider will give you a pregnancy test before
you start treatment
- You should use an effective method of birth control during your
treatment and for at least 4 months after your last dose of
LIBTAYO. Talk to your healthcare provider about birth control
methods that you can use during this time
- Tell your healthcare provider right away if you become pregnant
or think you may be pregnant during treatment with LIBTAYO
- are breastfeeding or plan to breastfeed. It is not known if
LIBTAYO passes into your breast milk. Do not breastfeed during
treatment and for at least 4 months after the last dose of
LIBTAYO
Tell your healthcare provider about all the medicines
you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
The most common side effects of LIBTAYO when used alone include
tiredness, muscle or bone pain, rash, diarrhea, and low levels of
red blood cells (anemia). The most common side effects of LIBTAYO
when used in combination with platinum-containing chemotherapy
include hair loss, muscle or bone pain, nausea, tiredness,
numbness, pain, tingling, or burning in your hands or feet, and
decreased appetite. These are not all the possible side effects of
LIBTAYO. Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088. You may also
report side effects to Regeneron Pharmaceuticals at
1-877-542-8296.
Please see full Prescribing
Information,
including Medication
Guide.
About
Regeneron's VelocImmune TechnologyRegeneron'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® (dupilumab), Libtayo®,
Praluent® (alirocumab), Kevzara® (sarilumab),
Evkeeza® (evinacumab-dgnb) and Inmazeb® (atoltivimab,
maftivimab and odesivimab-ebgn).
About RegeneronRegeneron is a leading
biotechnology company that invents, develops and commercializes
life-transforming medicines for people with serious diseases.
Founded and led for 35 years by physician-scientists, our unique
ability to repeatedly and consistently translate science into
medicine has led to nine FDA-approved treatments and numerous
product candidates in development, almost 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, hematologic conditions, 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 more information, please
visit www.Regeneron.com or follow @Regeneron on
Twitter.
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 fianlimab in combination with Libtayo®
(cemiplimab); the likelihood, timing, and scope of possible
regulatory approval and commercial launch of Regeneron’s Product
Candidates and new indications for Regeneron’s Products,
including fianlimab in combination with Libtayo for the
treatment of advanced melanoma as well as Libtayo (as a monotherapy
or in combination with conventional or novel therapeutic
approaches, as applicable) for other solid tumors and blood cancers
and Regeneron’s investigational bispecific antibodies referenced in
this press release; 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 and Regeneron's Product Candidates
(such as fianlimab); 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
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, Praluent® (alirocumab), and REGEN-COV® (casirivimab
and imdevimab)), 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, 2022 and its Form 10-Q for the
quarterly period ended March 31, 2023. 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 or otherwise) 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).
Contacts:Media
Relations Ashley
Buford Tel: +1
914-356-2235ashely.buford@regeneron.com |
Investor RelationsVesna TosicTel:
+1 914-847-5443vesna.tosic@regeneron.com |
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