TARRYTOWN, N.Y., Dec.
8, 2019 /PRNewswire/ -- Regeneron Pharmaceuticals,
Inc. (NASDAQ: REGN) today announced initial clinical
data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with
relapsed or refractory (R/R) multiple myeloma. BCMA (B-cell
maturation antigen) is a protein that is typically over-expressed
on multiple myeloma cells. REGN5458 is designed to bind to BCMA on
multiple myeloma cells and the CD3 receptor on T-cells, bridging
them together and activating T-cell killing of the cancer cell.
Results were presented today at the American Society of
Hematology (ASH) Annual Meeting from the first two dose groups (3
mg and 6 mg weekly doses). Patients had a median of seven lines of
prior systemic therapy, and all had failed CD38 antibody treatment.
Responses were observed in 4 of 7 (57%) patients, including 3 of 4
(75%) in the 6 mg dose group. In the 6 mg dose group, 2 patients
(50%) were also minimal residual disease (MRD) negative, meaning
that no cancer cells were detectable in their bone marrow.
"We are encouraged to see promising, rapid clinical activity
even at the initial two doses of REGN5458 in heavily pretreated
patients with multiple myeloma. Two patients achieved the high bar
of MRD negativity, and another patient attained a very good partial
response despite entering the trial with difficult-to-treat
plasmacytomas outside of the bone marrow," said Israel Lowy, M.D., Ph.D., Senior Vice President
and Head of Clinical and Translational Sciences for Oncology at
Regeneron. "We are actively recruiting patients into higher
dose groups in this trial and look forward to sharing further
results in 2020. In addition, we have also initiated a clinical
trial for our second BCMAxCD3 bispecific, REGN5459, which has
different binding characteristics."
REGN5458 and REGN5459 were invented using Regeneron's next
generation VelocImmune® "human
antibody mouse" technology, together with its
VelociBi™ platform. These allow for the
creation of bispecific antibodies that closely resemble natural
human antibodies with no linkers or artificial sequences.
Additionally, Regeneron bispecifics are manufactured using similar
approaches used for human antibody medicines, with similar
pharmacokinetics.
As of data cutoff, there have been no neurotoxicity,
dose-limiting toxicities or treatment discontinuations due to
adverse events (AEs). The most common treatment-emergent AEs were
lymphopenia (n=5), anemia (n=4) and thrombocytopenia and cytokine
release syndrome (n=3 each). Grade 3 or higher treatment-emergent
AEs were seen in 5 patients and included lymphopenia (n=3),
hypertension (n=2) and anemia, atrial fibrillation, fatigue,
febrile neutropenia, pain in extremity, septic shock and
thrombocytopenia (n=1 each).
Multiple myeloma is the second most common blood cancer, with
approximately 32,000 and 138,500 new diagnoses in the U.S. and
world respectively. It is characterized by the proliferation of
cancerous plasma cells (multiple myeloma cells) that crowd out
healthy blood cells in the bone marrow, infiltrate other tissues
and cause potentially life-threatening organ injury. Recent
advances, such as CD38 antibody treatment, have increased life
expectancy of patients from 3-4 years to 7-8 years. Despite this,
multiple myeloma remains incurable, and most patients will
experience relapse and require additional therapy.
The REGN5458 data follow other positive results from Regeneron's
growing bispecific pipeline, including updated REGN1979 data that
will be presented at ASH. REGN1979 is an investigational CD3
bispecific that is being studied in R/R follicular lymphoma and
diffuse large B-cell lymphoma, including in patients whose cancer
did not respond to CAR-T therapy. Regeneron has also invented a
second class of CD28 bispecifics, called co-stimulatory
bispecifics, which have recently entered clinical trials.
About the REGN5458 Phase 1/2 Dose-escalation
Trial
REGN5458 monotherapy is being investigated in an
open-label, Phase 1/2 dose-escalation trial in patients with R/R
multiple myeloma who have exhausted all therapeutic options,
including proteasome inhibitors, immunomodulatory drugs and CD38
antibody treatments. The Phase 1 portion is assessing safety,
tolerability and dose-limiting toxicities. Beyond the initial dose
groups presented at ASH, additional dose groups are being evaluated
to determine a recommended Phase 2 dose regimen. The Phase 2
portion will further assess REGN5458 anti-tumor activity and
safety.
Among the patients being enrolled are those with heavily
pre-treated multiple myeloma, including those with extra-medullary
(outside of the bone marrow) and non-secretory disease (do not
secrete detectable myeloma proteins).
In multiple myeloma clinical trials, treatment effectiveness is
typically assessed by overall response rate (ORR; with response
types categorized by the level of reduction in myeloma protein) and
the rate of conversion to negative MRD (which measures the
eradication of myeloma cells in bone marrow). For ORR, myeloma
protein levels in the blood are reduced by more than 50% in partial
responses (PR) and 90% in very good PR (VGPR), while complete
responses are defined as no evidence of myeloma protein and ≤5% of
plasma cells in the bone marrow. MRD is measured separately from
ORR, and MRD negativity is defined as the absence of myeloma cells
within 100,000 bone marrow cells.
About the Regeneron Bispecific Antibody Platform
All
of Regeneron's bispecific antibodies are designed to closely
resemble natural human antibodies. They are derived from a
next-generation version of Regeneron's proprietary
VelocImmune technology and created using the company's
VelociBi platform.
There are six Regeneron investigational bispecific antibodies
currently in ongoing clinical trials for multiple blood cancers and
solid tumors. These bispecifics fall into three categories:
-- CD3 bispecifics are designed to bridge T-cells and
tumor cells. At the tumor site, they activate T-cells via their CD3
receptors and promote T-cell killing of the cancer cells.
Investigational candidates include:
- CD20xCD3 (REGN1979) for non-Hodgkin B-cell lymphomas;
- Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple
myeloma;
- MUC16xCD3 (REGN4018) for ovarian cancer.
-- CD28 costimulatory bispecifics are also designed
to bridge T-cells and tumor cells. At the tumor site, they
costimulate T-cells via their CD28 receptors and may synergize with
PD-1 inhibitors and/or CD3 bispecifics. Investigational candidates
include:
- PSMAxCD28 (REGN5678) in combination with
Libtayo® (cemiplimab) for prostate
cancer.
-- Tumor-targeted bispecifics are designed
to target proteins only on the cancer cell. In this way, they
may affect various signaling pathways to hamper the cancer cells'
ability to survive and proliferate. Investigational candidates
include:
- METxMET (REGN5093) for non-small cell lung cancer that is
driven by MET mutations and/or amplifications. REGN5093 targets two
different parts of the MET receptor on cancer cells to degrade the
receptor and block its ability to trigger cell proliferation.
Regulatory Status of Oncology Programs
REGN1979,
REGN5458, REGN5459, REGN4018, REGN5678, REGN5093 and Libtayo are
currently under clinical development for the diseases noted in this
press release, and their safety and efficacy have not been
evaluated by any regulatory authority for these diseases. As part
of a global collaboration agreement, Regeneron and Sanofi are
jointly developing Libtayo, as well as Regeneron's BCMAxCD3 and
MUC16xCD3 bispecific programs.
Libtayo is approved in the U.S. for the treatment of patients
with metastatic cutaneous squamous cell carcinoma (CSCC) or locally
advanced CSCC who are not candidates for curative surgery or
curative radiation, and in other countries for similar indications.
In the U.S., the generic name for Libtayo 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.
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, infectious diseases,
pain and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune®, which uses a unique
genetically-humanized mouse 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.
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 nature, timing, and
possible success and therapeutic applications of Regeneron's
products, product candidates, and research and clinical programs
now underway or planned, including without limitation REGN5458 (a
BCMAxCD3 bispecific antibody) in patients with relapsed or
refractory multiple myeloma, as well as REGN5459 (a BCMAxCD3
bispecific antibody), REGN1979 (a CD20xCD3 bispecific antibody),
REGN4018 (a MUC16xCD3 bispecific antibody), REGN5678 (a PSMAxCD28
bispecific antibody), REGN5093 (a METxMET bispecific antibody), and
Regeneron's earlier-stage product candidates (as a monotherapy or
in combination with Libtayo® (cemiplimab),
as applicable); unforeseen safety issues resulting from the
administration of products and product candidates in patients,
including serious complications or side effects in connection with
the use of Regeneron's product candidates (such as REGN5458,
REGN5459, REGN1979, REGN4018, REGN5678, and REGN5093) in clinical
trials; the extent to which the results from the research and
development programs conducted by Regeneron or its collaborators
(including the open-label, Phase 1/2 dose-escalation trial
evaluating REGN5458 discussed in this press release) may be
replicated in other studies and lead to therapeutic applications;
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; ongoing regulatory
obligations and oversight impacting Regeneron's marketed products,
research and clinical programs, and business, including those
relating to patient privacy; 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; competing drugs and
product candidates that may be superior to Regeneron's products and
product candidates; 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 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, labeling,
distribution, and other steps related to Regeneron's products and
product candidates; the availability and extent of reimbursement of
the Company'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; 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
fiscal year ended December 31, 2018
and its Form 10-Q for the quarterly period ended September 30, 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).
Contacts:
Media Relations
Daren Kwok
Tel: +1 (914) 598-7590
Daren.Kwok@regeneron.com
Investor Relations
Justin Holko
Tel: +1 (914) 847-7786
Justin.Holko@regeneron.com
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SOURCE Regeneron Pharmaceuticals, Inc.