Ide-cel, an investigational CAR T cell
therapy for multiple myeloma, met primary endpoint and key
secondary endpoints
Pivotal study results demonstrated deep and
durable responses in a heavily pre-treated and highly refractory
patient population
Bristol Myers Squibb (NYSE: BMY) and bluebird bio, Inc. (Nasdaq:
BLUE) today announced updated results from the pivotal, Phase 2
KarMMa study evaluating the efficacy and safety of the companies’
investigational B-cell maturation antigen (BCMA)-directed chimeric
antigen receptor (CAR) T cell immunotherapy, idecabtagene vicleucel
(ide-cel; bb2121), in patients with relapsed and refractory
multiple myeloma. These data will be shared in an oral presentation
at the American Society of Clinical Oncology 2020 (ASCO20) Virtual
Scientific Program on May 29 at 8:00 AM ET.
In the study, 128 patients with heavily pretreated relapsed and
refractory multiple myeloma who were exposed to at least three
prior therapies and were refractory to their last regimen per the
International Myeloma Working Group (IMWG) definition (no response
to therapy or disease progressed within 60 days) were treated with
ide-cel across target dose levels of 150-450 x 106 CAR+ T cells.
Patients had a median of six prior regimens; 84% were refractory to
all three classes of commonly used treatments including an
immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an
anti-CD38 antibody, and 94% were refractory to anti-CD38
antibodies. Median duration of follow-up was 13.3 months.
The overall response rate (ORR) was 73% across all dose levels,
including 33% of patients who had a complete response (CR) or
stringent CR (sCR). Median duration of response (DoR) was 10.7
months, with 19.0 month median DoR for patients who had a CR or
sCR. Median progression-free survival (PFS) was 8.8 months, with
20.2 month median PFS for patients who had a CR or sCR. All
patients who had CR or sCR and were evaluable for minimal residual
disease (MRD), were MRD-negative. Clinically meaningful benefit was
consistently observed across subgroups, and nearly all subgroups
had an ORR of 50% or greater, including older and high-risk
patients. The overall survival (OS) data continue to mature, with
an estimated median OS of 19.4 months across all dose levels and
78% of patients alive at 12 months.1 Results support a favorable
benefit-risk profile for ide-cel across the target dose levels of
150 to 450 × 106 CAR+ T cells.
Ide-cel Treated Population
Across Dose Range*
Dose, x 106 CAR+ T cells
150
(n=4)
300
(n=70)
450
(n=54)
150-450
(n=128)
ORR, n (%)
2 (50)
48 (69)
44 (82)
94 (73)
CR/sCR, n (%)
1 (25)
20 (29)
21 (39)
42 (33)
Median DoR, mo
Median DoR by best response (CR/sCR),
mo
-†
-†
9.9
-††
11.3
-††
10.7
19.0
Median PFS, mo
Median PFS by best response (CR/sCR),
mo
2.8
-†
5.8
-††
12.1
-††
8.8
20.2
*Data have been updated following abstract publication †Not
reported due to small n ††Data not reported
The most frequently reported adverse events (AEs) were cytopenia
and cytokine release syndrome (CRS). Cytopenias were common and not
dose related. Overall, CRS of any grade was reported in 84%
(107/128) of patients. Grade 3 or higher CRS occurred in
<6% (7/128) of patients, with one
fatal CRS event. Investigator identified neurotoxicity events
(iiNT) were reported in 18% (23/128) of patients, including Grade 3
iiNT reported in 3% (4/128) of patients. There were no Grade 4 or
Grade 5 iiNT events reported.2
“We are very encouraged and excited by the depth and durability
of responses seen with ide-cel in this first pivotal study of a CAR
T cell therapy in multiple myeloma. Patients with relapsed and
refractory multiple myeloma have decreased life expectancy, with no
clear standard of care and limited responses to currently available
treatment options, leaving them in critical need of new therapies,”
said Nikhil C. Munshi, M.D., presenting author, Associate Director,
The Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer
Institute, Boston, Massachusetts. “The hematology and oncology
community looks forward to the potential application of ide-cel in
future clinical practice.”
“These longer-term results from the KarMMa study further
demonstrate the clinical benefit of ide-cel and support its role as
a potentially important therapeutic option for patients with
triple-class exposed, relapsed and refractory multiple myeloma,”
said Kristen Hege, M.D., senior vice president, Hematology/Oncology
and Cell Therapy, Early Clinical Development, Bristol Myers Squibb.
“BMS and bluebird bio remain focused on improving outcomes in this
population and bringing ide-cel to patients as quickly as
possible.”
“Patients in the KarMMa study reflect a very advanced and highly
refractory population, so it is particularly gratifying that the
results announced today from the pivotal KarMMa study,
demonstrating deep and durable responses, underscore the potential
of ide-cel as a meaningful new treatment option for these
patients,” said David Davidson, M.D., Chief Medical Officer,
bluebird bio. “bluebird bio, together with our partners at Bristol
Myers Squibb, understands the urgency to deliver new therapeutic
options for patients living with relapsed and refractory multiple
myeloma, and we are committed to bringing this potentially
first-in-class BCMA-directed CAR T cell therapy to patients in
need.”
Ide-cel is not approved for any indication in any geography.
About Ide-cel
Ide-cel is a B-cell maturation antigen (BCMA)-directed
genetically modified autologous chimeric antigen receptor (CAR) T
cell immunotherapy. The ide-cel CAR is comprised of a murine
extracellular single-chain variable fragment (scFv) specific for
recognizing BCMA, attached to a human CD8 α hinge and transmembrane
domain fused to the T cell cytoplasmic signaling domains of CD137
4-1BB and CD3-� chain, in tandem. Ide-cel recognizes and binds to
BCMA on the surface of multiple myeloma cells leading to CAR T cell
proliferation, cytokine secretion, and subsequent cytolytic killing
of BCMA-expressing cells.
Bristol Myers Squibb and bluebird bio’s broad clinical
development program for ide-cel includes clinical studies
(KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for
patients with multiple myeloma, including newly diagnosed multiple
myeloma. For more information visit clinicaltrials.gov.
Ide-cel is being developed as part of a Co-Development,
Co-Promotion and Profit Share Agreement between Bristol Myers
Squibb and bluebird bio.
About KarMMa3
KarMMa (NCT03361748) is a pivotal, open-label, single-arm,
multicenter, multinational, Phase 2 study evaluating the efficacy
and safety of ide-cel in adults with relapsed and refractory
multiple myeloma in North America and Europe. The primary endpoint
of the study is overall response rate as assessed by an independent
review committee (IRC) according to the International Myeloma
Working Group (IMWG) criteria. Complete response rate is a key
secondary endpoint. Other efficacy endpoints include time to
response, duration of response, progression-free survival, overall
survival, minimal residual disease evaluated by Next-Generation
Sequencing (NGS) assay and safety. The study enrolled 140 patients,
of whom 128 received ide-cel across the target dose levels of
150-450 x 106 CAR+ T cells after receiving lymphodepleting
chemotherapy. All enrolled patients had received at least three
prior treatment regimens, including an immunomodulatory agent, a
proteasome inhibitor and an anti-CD38 antibody, and were refractory
to their last regimen, defined as progression during or within 60
days of their last therapy.
Bristol Myers Squibb: Advancing Cancer
Research
At Bristol Myers Squibb, patients are at the center of
everything we do. The goal of our cancer research is to increase
patients’ quality of life, long-term survival and make cure a
possibility. We harness our deep scientific experience,
cutting-edge technologies and discovery platforms to discover,
develop and deliver novel treatments for patients.
Building upon our transformative work and legacy in hematology
and Immuno-Oncology that has changed survival expectations for many
cancers, our researchers are advancing a deep and diverse pipeline
across multiple modalities. In the field of immune cell therapy,
this includes registrational CAR T cell agents for numerous
diseases, and a growing early-stage pipeline that expands cell and
gene therapy targets, and technologies. We are developing cancer
treatments directed at key biological pathways using our protein
homeostasis platform, a research capability that has been the basis
of our approved therapies for multiple myeloma and several
promising compounds in early- to mid-stage development. Our
scientists are targeting different immune system pathways to
address interactions between tumors, the microenvironment and the
immune system to further expand upon the progress we have made and
help more patients respond to treatment. Combining these approaches
is key to delivering potential new options for the treatment of
cancer and addressing the growing issue of resistance to
immunotherapy. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines a reality for patients.
About Bristol Myers
Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of
Bristol-Myers Squibb Company. In certain countries outside the
U.S., due to local laws, Celgene and Juno Therapeutics are referred
to as, Celgene, a Bristol Myers Squibb company and Juno
Therapeutics, a Bristol Myers Squibb company.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our
Cambridge, Mass., headquarters, we’re developing gene therapies for
severe genetic diseases and cancer, with the goal that people
facing potentially fatal conditions with limited treatment options
can live their lives fully. Beyond our labs, we’re working to
positively disrupt the healthcare system to create access,
transparency and education so that gene therapy can become
available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re
putting our care and expertise to work across a spectrum of
disorders including cerebral adrenoleukodystrophy, sickle cell
disease, β-thalassemia and multiple myeloma using three gene
therapy technologies: gene addition, cell therapy and
(megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham,
N.C.; and Zug, Switzerland. For more information, visit
bluebirdbio.com.
Follow bluebird bio on social media: @bluebirdbio, LinkedIn,
Instagram and YouTube.
bluebird bio is a trademark of bluebird bio, Inc.
Bristol Myers Squibb Cautionary
Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that ide-cel, or bb2121, may not achieve its
primary study endpoints or receive regulatory approval for the
indication described in this release in the currently anticipated
timeline or at all and, if approved, whether such product candidate
for such indication described in this release will be commercially
successful. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be
evaluated together with the many risks and uncertainties that
affect Bristol Myers Squibb’s business and market, particularly
those identified in the cautionary statement and risk factors
discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for
the year ended December 31, 2019, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
other filings with the Securities and Exchange Commission. The
forward-looking statements included in this document are made only
as of the date of this document and except as otherwise required by
applicable law, Bristol Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
or otherwise.
bluebird bio Cautionary Statement
Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, the possibility of unfavorable results from
additional clinical trials of ide-cel, that ide-cel may not receive
regulatory approval for the indication described in this release in
the currently anticipated timeline or at all and, if approved,
whether such product candidate for such indication described in
this release will be commercially successful, and that the
collaboration with Bristol Myers Squibb may not continue or be
successful. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be
evaluated together with the many risks and uncertainties that
affect bluebird bio’s business, particularly those identified in
the risk factors discussion in bluebird bio’s Annual Report on Form
10-K for the year ended December 31, 2019, as updated by our
subsequent Quarterly Reports on Form 10-Q, Current Reports on Form
8-K and other filings with the Securities and Exchange Commission.
The forward-looking statements included in this document are made
only as of the date of this document and except as otherwise
required by applicable law, bluebird bio undertakes no obligation
to publicly update or revise any forward-looking statement, whether
as a result of new information, future events, changed
circumstances or otherwise.
Hyperlinks are provided as a convenience and for informational
purposes only. Neither Bristol Myers Squibb nor bluebird bio bears
responsibility for the security or content of external websites or
websites outside of their respective control.
References
- Munshi NC, et al. Idecabtagene vicleucel (ide-cel; bb2121), a
BCMA-targeted CAR T cell therapy, in patients with relapsed and
refractory multiple myeloma (RRMM): initial KarMMa results. ASCO
2020 Virtual Scientific Program. Abstract #39T850339T.
- Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy
bb2121 in relapsed or refractory multiple myeloma. N Engl J Med.
2019 May 2;380(18):1726-1737.
- ClinicalTrials.gov. Efficacy and safety study of bb2121 in
subjects with relapsed and refractory multiple myeloma (KarMMA).
Available at: https://clinicaltrials.gov/ct2/show/NCT03361748.
Accessed May 2020.
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