High rates of response that were both deep and
durable were seen at the highest dose levels.
Median PFS of approximately one year achieved
in heavily pre-treated patients in the active doses of the dose
escalation cohort
Consistent response observed for both low and
high BCMA expression levels
Adverse events have been manageable across
doses
Celgene Corporation (NASDAQ:CELG) and bluebird bio, Inc. (NASDAQ:BLUE) today announced updated
results from the ongoing CRB-401 phase I clinical study of bb2121,
an investigational anti-B-cell maturation antigen (BCMA) CAR T cell
therapy, in 43 patients with late-stage relapsed/refractory
multiple myeloma. These data were the subject of an oral
presentation by Noopur Raje, M.D. at the American Society of
Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.
“We are encouraged by the continuing deep and durable responses
seen in this study and look forward to the results of our pivotal
study, KarMMa, which is currently enrolling,” said Jay Backstrom,
Chief Medical Officer for Celgene. “We continue to see BCMA as an
excellent target in multiple myeloma and we believe bb2121 has the
potential to have a significant impact on the treatment approach
and outcomes for these patients. We and our partners at bluebird
bio are fully committed to the continued rapid clinical development
of bb2121 and the evaluation of its potential in the treatment of
patients with relapsed and refractory multiple myeloma.”
“To see a median PFS of 11.8 months in this heavily pretreated
patient population is very encouraging,” said David Davidson, M.D.,
Chief Medical Officer, bluebird bio. “As the data from this program
continue to mature, bb2121 has set a high bar as the leading
investigational anti-BCMA CAR T cell candidate for relapsed and
refractory multiple myeloma. In addition, the deep MRD-negative
responses, the activity seen across myeloma with high and low
levels of BCMA expression, as well as adverse events observed
support the evaluation of bb2121 in earlier lines of multiple
myeloma, where patients may experience more durable outcomes.”
The open-label phase I CRB-401 study (NCT02658929) is evaluating
the preliminary safety and efficacy of bb2121 anti-BCMA CAR T cell
therapy in patients with relapsed/refractory multiple myeloma.
Patients in the study were heavily pre-treated, with a median of
seven prior myeloma treatment regimens (min, max: 3,14) in the dose
escalation cohort (n=21) and eight prior regimens (min, max: 3, 23)
in the dose expansion cohort (n=22). More than 90% of patients had
received prior treatment with two IMiD® therapies, two proteasome
inhibitors, daratumumab and an autologous stem cell transplant.
As of the March 29, 2018 data cut-off, 43 patients had been
enrolled and dosed in either the dose-escalation cohort of the
study, at four dose levels (50 x 106, 150 x 106, 450 x 106 and 800
x 106 CAR+ T cells), or in the dose expansion cohort in a dose
range between 150-450 x 106 CAR+ T cells.
Patients received a lymphodepleting conditioning regimen of
fludarabine and cyclophosphamide, followed by an infusion of bb2121
anti-BCMA CAR T cells. The CAR T cells were produced from each
patient’s own blood cells, which were modified using a proprietary
lentiviral vector encoding the anti-BCMA CAR.
Response outcomes in efficacy evaluable patients* in the
study were as follows:
Measure
50 x 106 (n=3),
median follow-up 84
days (59,94)
150 x 106 (n=14),
median follow-up 87
days (36,638)
>150 x 106 (n=22),
median follow-up 194
days (46, 556)
Overall response
(ORR)
33.3% 57.1% 95.5%
Complete response
(CR)
0% 42.9% 50%
Very good partial
response (VGPR)
0% 7.1% 36.4%
Median duration of
response mDOR
1.9 months Not estimable 10.8 months
*Patients with ≥2 months of response data
or PD/death within <2 months
Responses were dose-related and observed for both low and high
BCMA expression levels. In patients treated with 450 x 106 CAR+ T
cells whose myeloma cells expressed low levels of BCMA (0 to 50% of
cells BCMA positive), 8 of 8 had a response. In those expressing
high BCMA (≥50% BCMA positive), 10 of 11 had a response.
The median progression-free survival (PFS) estimate for patients
in the dose-escalation phase treated at active doses (≥150 x 106
CAR+ T cells) was 11.8 months (95% CI 8.8, NE), while patients
receiving 50 x 106 CAR+ T cells had a median PFS of 2.7 months (95%
CI 1.0, 2.9).
In the dose-escalation and expansion phase of the study, all
patients who responded and were evaluable for minimal residual
disease (MRD as measured by adaptive next-generation sequencing
assay) (n=16) were MRD negative at one or more time points.
Additionally, two patients who did not have a response and were
evaluated for MRD were MRD positive at month one. The median PFS
estimate in MRD negative responders was 17.7 months (95% CI: 5.8,
NE).
Among all infused patients (n=43), 63% had cytokine release
syndrome (CRS), mostly Grade 1 & 2, with 2 patients
experiencing Grade 3 CRS (5%). Nine patients (21%) received
tocilizumab, including 4 patients (9%) who also received steroids
and the median duration of CRS was 6 days (1,32). For patients
receiving 150 x 106 CAR+ T cells (n=18), the rate of CRS was 39%
with no grade 3 cases. For patients receiving ≥150 x 106 CAR+ T
cells (n=22), the rate of CRS was 82% with 9.1% of patients
experiencing grade 3 events. Also among all infused patients, there
were 14 patients (33%) who experienced neurotoxicity, with one
patient experiencing a grade 3 or higher event. Other frequent
Grade 3/4 AEs included cytopenias commonly associated with
lymphodepleting chemotherapy such as neutropenia (79%),
thrombocytopenia (51%) and anemia (44%), as well as infection (any
grade) with a frequency of 61% overall and 23% in the first month.
Grade 3 or higher infection occurred with a frequency of 21%
overall and 5% in the first month.
“The continuing high, durable response rates and MRD-negative
results in this heavily pre-treated population of multiple myeloma
patients further illustrates BCMA as a promising target in this
incurable disease and bb2121 as an investigational therapy of great
potential in patients with relapsed and refractory multiple myeloma
with both high and low BCMA expression,” said Dr. Raje., Professor
of Medicine at Harvard Medical School and Director of the Multiple
Myeloma Center at Massachusetts General Hospital. “We will continue
to evaluate the long-term effect of bb2121 as we learn more about
the potential for this investigational therapy.”
bb2121 is an investigational compound that is not approved for
any use in any country. bb2121 received Breakthrough Therapy
Designation from the U.S. FDA and PRIME eligibility from the EMA.
Celgene has also sponsored an open-label, single-arm, pivotal,
phase 2 study (KarMMa), which is recruiting in North America and
Europe, to evaluate bb2121 further in patients with relapsed and
refractory multiple myeloma (NCT03361748).
About Celgene
Celgene Corporation, headquartered in Summit, New
Jersey, is an integrated global biopharmaceutical company engaged
primarily in the discovery, development and commercialization of
innovative therapies for the treatment of cancer and inflammatory
diseases through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com. Follow
Celgene on Social
Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy
expertise and gene editing capabilities, bluebird bio has built an
integrated product platform with broad potential application to
severe genetic diseases and cancer. bluebird bio's gene therapy
clinical programs include Lenti-D™ for the treatment of cerebral
adrenoleukodystrophy, and LentiGlobin™ for the treatment of
transfusion-dependent β-thalassemia, also known as β-thalassemia
major, and severe sickle cell disease. bluebird bio's oncology
pipeline is built upon the company's leadership in lentiviral gene
delivery and T cell engineering, with a focus on developing novel T
cell-based immunotherapies, including chimeric antigen receptor
(CAR T) and T cell receptor (TCR) therapies. bluebird bio's lead
oncology programs, bb2121 and bb21217, are anti-BCMA CAR T programs
partnered with Celgene. bluebird bio also has discovery research
programs utilizing megaTAL/homing endonuclease gene editing
technologies with the potential for use across the company's
pipeline.
bluebird bio has operations in Cambridge, Massachusetts,
Seattle, Washington, Durham, North Carolina and Zug,
Switzerland.
LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. Such forward-looking statements include those regarding the
potential benefits of, and plans relating to the collaboration
between bluebird bio and Celgene; the potential of bb2121 as a
therapeutic drug; and the benefit of each company’s strategic plans
and focus. The words “anticipate,” “believe,” “estimate,” “expect,”
“intend,” “may,” “plan,” “predict,” “project,” “would,” “could,”
“potential,” “possible,” “hope” and similar expressions are
intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Such
statements are subject to numerous important factors, risks and
uncertainties that may cause actual events or results to differ
materially from current expectations and beliefs. For example,
there can be no guarantee that any product candidate will be
successfully developed or complete necessary preclinical and
clinical phases, or that development of any of product candidates
will successfully continue. There can be no guarantee that any
positive developments will result in stock price appreciation.
Management's expectations and, therefore, any forward-looking
statements in this press release could also be affected by risks
and uncertainties relating to a number of other important factors,
including: results of clinical trials and preclinical studies,
including subsequent analysis of existing data and new data
received from ongoing and future studies; the content and timing of
decisions made by the U.S. FDA and other regulatory authorities,
investigational review boards at clinical trial sites and
publication review bodies; the ability to obtain and maintain
requisite regulatory approvals and to enroll patients in planned
clinical trials; unplanned cash requirements and expenditures;
competitive factors; the ability to obtain, maintain and enforce
patent and other intellectual property protection for any product
candidates; the ability to maintain key collaborations; and general
economic and market conditions. These and other risks are described
in greater detail under the caption "Risk Factors" included in each
company’s public filings with the Securities and Exchange
Commission. Any forward-looking statements contained in this press
release speak only as of the date hereof, and neither company has
any obligation to update any forward-looking statements, whether as
a result of new information, future events or otherwise, except as
may be required by law.
Hyperlinks are provided as a convenience and for informational
purposes only. Neither Celgene nor bluebird bio bears
responsibility for the security or content of external websites or
websites outside of their respective control.
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version on businesswire.com: https://www.businesswire.com/news/home/20180601005907/en/
For Celgene:Investors:Patrick Flanigan,
908-673-9969pflanigan@celgene.comorMedia:Greg Geissman,
908-673-9854ggeissman@celgene.comorFor bluebird
bioInvestors:Elizabeth Pingpank,
617-914-8736epingpank@bluebirdbio.comorMedia:Stephanie Fagan,
201-572-9581sfagan@bluebirdbio.com
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