TARRYTOWN, N.Y., Dec. 5, 2020 /PRNewswire/ --
63% response rate in patients treated with the highest
reported dose
Among all patients responding to treatment, 95% experienced a
very good partial response or better; among responding patients
with ≥6 months of follow-up, 83% have ongoing responses for
up to 13 months at the time of analysis
Potentially registrational Phase 2 portion of the trial has
been initiated and is enrolling patients
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced
updated data for REGN5458, a BCMAxCD3 bispecific antibody, from the
Phase 1 portion of a Phase 1/2 trial in patients with relapsed
or refractory (R/R) multiple myeloma. The results were shared in an
oral presentation at the virtual 2020 American Society of
Hematology (ASH) Annual Meeting. 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 in order to bridge them
together and activate T-cells to kill the cancer cells.
"REGN5458 continues to show early, deep and durable anti-tumor
responses in patients with relapsed and refractory multiple myeloma
across all dose levels. This is particularly encouraging given that
a majority of patients were heavily pretreated and had few options
remaining. All patients were triple-refractory, with 57% being
penta-refractory," said Deepu
Madduri, M.D., Assistant Professor of Medicine at the Icahn
School of Medicine at Mount Sinai
in New York and a trial
investigator. "As these data continue to mature, we look forward to
assessing whether responses will further deepen and remain durable
with ongoing REGN5458 treatment."
In the trial, the 49 patients evaluated had a median of five
prior lines of therapy (range: 2-17) with 100% being
triple-refractory and 57% being penta-refractory; all patients were
refractory to anti-CD38 therapy. With a median follow up of 2.6
months (range: 1-13), responses generally occurred by week 4 and
deepened over time. Exploratory analyses suggest that
patient-reported global health status/quality of life (per EORTC
QLQ-C30) also improved meaningfully at week 4 and was maintained
through week 24, with assessment ongoing.
Efficacy results, a secondary endpoint, by dose level were as
follows:
%
(n)
|
Dose Levels 1, 2,
3
(3, 6, 12 mg;
n=24)
|
Dose Levels 4,
5
(24, 48 mg;
n=17)
|
Dose Level
6
(96 mg;
n=8)
|
Median follow-up
(range)
|
3 months
(1-13
months)
|
3 months
(1-9
months)
|
2 months
(1-6
months)
|
Overall response
rate (ORR)
|
29% (7)
|
41% (7)
|
63% (5)
|
Complete response
(CR) or stringent CR (sCR)
|
21% (5)
|
18% (3)
|
0% (0)*
|
Very good partial
response (VGPR)
|
4% (1)
|
24% (4)
|
63% (5)
|
Partial response
(PR)
|
4% (1)
|
0% (0)
|
0% (0)
|
*As of data cut-off, dose level 6 patients had been followed for
a median of 2 months, and responses may deepen over
time.
Among all patients who responded to treatment (n=19) as of data
cut-off:
- 95% (n=18) achieved a VGPR or better
- 42% (n=8) had a CR or sCR
- 57% of evaluable patients (4 of 7 patients) were minimal
residual disease (MRD) negative
- Tumor response was not correlated with BCMA expression as
assessed by immunohistochemistry
In assessing durability among patients who responded to
treatment and with data continuing to mature at the time of
analysis:
- Among responding patients with ≥6 months of follow-up, 83% (10
of 12 patients) have ongoing responses for up to 13 months at the
time of analysis
- 74% of responders (n=14) remain on treatment
- The observed median duration of response was 6 months (range:
1-13)
The most common adverse events (AEs) were cytokine release
syndrome (CRS; 39%; n=19), anemia (37%; n=18), fatigue (35%; n=17),
nausea (31%; n=15), pyrexia (31%; n=15) and back pain (27%; n=13).
Grade ≥3 AEs occurred in 69% (n=34) of patients with the most
common being anemia (22%; n=11), neutropenia (14%; n=7) and
lymphopenia (12%; n=6). There were no reports of Grade ≥3 CRS or
neurotoxicity. Dose-limiting toxicity was reported in 2 patients
with 1 patient experiencing acute kidney injury and 1 patient
experiencing elevated alanine aminotransferase (ALT)/raised
aspartate aminotransferase (AST). Both cases were resolved with
supportive care, and the patient that experienced elevated ALT/AST
remains on REGN5458 and has since achieved a VGPR.
"REGN5458 is the second CD3 bispecific in our oncology portfolio
to show clinically meaningful results. Alongside our CD20xCD3
bispecific odronextamab, REGN5458 offers additional evidence to
support the potential of our bispecific platform to transform the
treatment of diverse blood cancers for patients," said L.
Andres Sirulnik, M.D., Ph.D., Senior
Vice President, Translational & Clinical Sciences, Hematology
at Regeneron. "Regeneron continues to drive increasing momentum
across our oncology and non-oncology hematology programs. We are
currently enrolling patients in a potentially registrational Phase
2 portion of this REGN5458 trial. We are also expanding our
odronextamab program with multiple pivotal trials in 2021."
In addition to the REGN5458 data, updated results from the Phase
1 odronextamab trial in R/R follicular lymphoma, diffuse large
B-cell lymphoma and other B-cell non-Hodgkin lymphomas will also be
shared in an oral presentation (Abstract 400) at ASH and will
include patient follow-up data of up to 3 years.
REGN5458 and odronextamab were invented using Regeneron's
proprietary VelocImmune® technology and created
using the company's Veloci-Bi® 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 monoclonal antibody
medicines, yielding similar properties and pharmacokinetics.
REGN5458 and odronextamab are currently under clinical
development, and their safety and efficacy have not been evaluated
by any regulatory authority.
About the 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 are
at least triple refractory to existing therapeutic options,
including proteasome inhibitors, immunomodulatory drugs and CD38
antibody treatments. The Phase 1 portion of the trial is primarily
assessing safety, tolerability, and dose-limiting toxicities of
REGN5458, with efficacy as secondary endpoints. The Phase 2 portion
is currently enrolling patients and will further assess REGN5458
anti-tumor activity and safety.
Among the patients being enrolled are those with heavily
pre-treated, triple refractory and penta-exposed multiple myeloma,
including those with extra-medullary (outside of the bone marrow)
and non-secretory (do not secrete detectable myeloma proteins)
disease.
About Multiple Myeloma
Multiple myeloma is the second
most common blood cancer with approximately 30,192 and 168,765 new
diagnoses in the U.S. and the world, respectively, in 2020. 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. Multiple myeloma is not curable
despite treatment advances. While current treatments are able to
slow progression of the cancer, most patients will ultimately
experience cancer progression and require additional therapies.
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 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, 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 impact of
SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on
Regeneron's business and its employees, collaborators, and
suppliers and other third parties on which Regeneron relies,
Regeneron's and its collaborators' ability to continue to conduct
research and clinical programs, Regeneron's ability to manage its
supply chain, net product sales of products marketed or otherwise
commercialized 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 Regeneron's product candidates and
research and clinical programs now underway or planned, including
without limitation REGN5458 (a BCMAxCD3 bispecific antibody) and
odronextamab (a CD20xCD3 bispecific antibody); 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 REGN5458 in
relapsed/refractory (R/R) multiple myeloma and other potential
indications and odronextamab in R/R stages of follicular lymphoma,
diffuse large B-cell lymphoma, other B-cell non-Hodgkin lymphomas,
and other potential indications; uncertainty of market
acceptance and commercial success of Regeneron's Products and
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Regeneron or others and whether mandated or voluntary), including
the studies discussed in this press release, on the commercial
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safety issues resulting from the administration of Regeneron's
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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
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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 product
candidates; the extent to which the results from the research and
development programs conducted by Regeneron and/or its
collaborators may be replicated in other studies and/or lead
to advancement of product candidates to clinical trials,
therapeutic applications, or regulatory approval; 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; 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, Bayer, and
Teva Pharmaceutical Industries Ltd. (or their respective affiliated
companies, as applicable), to be cancelled or terminated; 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, 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 and its Form 10-Q for the
quarterly period ended September 30,
2020. 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
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Regeneron
Contacts:
Media
Relations
Taylor
Ramsey
Tel: +1 (914)
409-2381
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Relations
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Tosic
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847-5443
vesna.tosic@regeneron.com
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