Celgene Corporation (Nasdaq: CELG) and bluebird bio, Inc.
(Nasdaq: BLUE) today announced that the New England Journal of
Medicine (NEJM) has published interim results from CRB-401, the
ongoing phase 1 study of bb2121, the companies’ lead
investigational BCMA-targeted chimeric antigen receptor (CAR)
T-cell therapy candidate for patients with relapsed and refractory
multiple myeloma.
The manuscript, “Anti-BCMA CAR T Cell Therapy bb2121 in
Relapsed/Refractory Multiple Myeloma”, published in NEJM includes
key safety and efficacy results from the dose escalation and first
expansion cohort, including a minimum of six months follow up on
all subjects. As of the data cut-off date of April 30, 2018,
manageable safety and deep and durable responses were reported in
the first 33 patients infused with bb2121 BCMA-targeted CAR
T-cells. Patients in the study were heavily pre-treated, with a
median of seven prior multiple myeloma treatment regimens (range, 3
to 23), which included prior treatment with immunomodulatory drugs,
proteasome inhibitors and daratumumab in the majority of patients.
All but one patient had previously received an autologous stem cell
transplant.
“CAR T-cell therapy is an important area of research for
relapsed/refractory multiple myeloma patients where there remains a
need for new options. We are encouraged by the expansion and
persistence of the CAR T-cells, as well as the deep and durable
responses with a manageable safety profile we’ve seen for bb2121 to
date,” said senior author and principal investigator James N.
Kochenderfer, M.D., Experimental Transplantation and Immunology
Branch, National Cancer Institute Center for Cancer Research.
For the first 33 patients, the most common grade ≥3 events were
hematologic toxicities, including neutropenia (85%), leukopenia
(58%), anemia (45%) and thrombocytopenia (45%). Neurotoxicity
all-grades occurred in 14 (42%) patients; 13 (39%) were grade ≤2
and one patient (3%) had grade 4 neurotoxicity which resolved
within one month. Twenty-five (76%) patients experienced cytokine
release syndrome; 23 (70%) were grade ≤2 events and two (6%) were
grade 3 events; all events were reversible. Infection occurred in
14 (42%) patients; two were grade 3 (6%) and there were no grade 4
events. Peak CAR T cell expansion was higher in patients with
cytokine release syndrome and CAR T-cells remained detectable in
the blood in 57% of patients at six months following infusion.
Treatment with bb2121 resulted in an 85% objective response rate
(ORR) with 45% of patients achieving a complete response (CR)
(n=15) and an additional 27% of patients (n=9) achieving a very
good partial response (VGPR) to yield a ≥ VGPR rate of 73%. Sixteen
responding patients were evaluable for assessment of minimal
residual disease (MRD) and all tested MRD negative at one or more
time points.
Responses to bb2121 CAR T-cell infusion occurred early, with a
median time to first partial response or better of 1.0 month
(range, 0.5 to 3.0), and responses were durable, with a median
duration of response of 10.9 months (95% CI, 7.2 to not estimable).
Researchers observed that greater CAR T-cell expansion occurred in
responding patients. Responses were observed independent of tumor
or serum BCMA levels. Median progression-free survival among all 33
patients was 11.8 months (95% CI, 6.2–17.8).
“These data from CRB-401 demonstrate that BCMA is a promising
target in the treatment of patients with multiple myeloma. We
continue to be encouraged by the potential of bb2121 as a
first-in-class BCMA-targeted CAR T-cell therapy,” said Alise
Reicin, M.D., President, Global Clinical Development for Celgene.
“The compelling data in these heavily pre-treated
relapsed/refractory patients has provided important insights in the
development of bb2121 as we continue the follow up of patients in
our recently fully enrolled pivotal KarMMa trial. We are also
evaluating the potential for bb2121 in earlier lines of multiple
myeloma treatment in the other KarMMa trials.”
"The data published in NEJM from CRB-401 provide the foundation
for advancing the development of bb2121, which is currently being
assessed in multiple clinical studies across different patient
populations within multiple myeloma,” said Dave Davidson, M.D.,
chief medical officer, bluebird bio. “We hope that this potentially
first-in-class BCMA-targeted CAR T-cell therapy may provide a new
treatment option for patients living with multiple myeloma.”
In November 2017, bb2121 was granted Breakthrough Therapy
Designation (BTD) by the U.S. Food and Drug Administration and
PRIority Medicines (PRIME) eligibility by the European Medicines
Agency based on preliminary clinical data from the phase 1 CRB-401
study.
bb2121 is being developed as part of a Co-Development,
Co-Promote and Profit Share Agreement between Celgene and bluebird
bio.
Potential approval of bb2121 in the U.S. is anticipated in the
second half of 2020. bb2121 is an investigational therapy; safety
and efficacy have not yet been established. bb2121 has not been
approved for use by any health authority.
About CRB-401
The open-label phase 1 CRB-401 study (NCT02658929) is evaluating
the preliminary safety and efficacy of bb2121 BCMA-targeted CAR
T-cell therapy in patients with relapsed/refractory multiple
myeloma. The primary endpoint of the study is safety. The first
portion of the study included a dose-escalation phase in which
cohorts of patients received ascending doses of bb2121 to determine
the maximum tolerated dose; these findings established the
recommended dose of the phase 2 KarMMa trial. The second portion of
the study was a dose expansion phase where patients received bb2121
to further evaluate the safety, tolerability and clinical activity
at the recommended phase 2 dose. All patients have been treated in
the study and follow-up is ongoing. Complete data from the
additional expansion cohorts will be published at a later date.
Patients in the dose escalation cohort and first expansion
cohort of the study were heavily pre-treated, with a median of
seven prior multiple myeloma treatment regimens (range: 3-14) in
the dose escalation cohort (n=21) and eight prior regimens (range:
3-23) in the dose expansion cohort (n=12). Patients in the dose
escalation phase had received at least three previous lines of
therapy, including a proteasome inhibitor and an immunomodulatory
agent, or were refractory to both drug classes. In addition,
patients in the expansion cohorts had received a CD38 antibody and
were refractory to their last regimen. All but one patient had
previously received an autologous stem cell transplant. As of the
data cut-off, patients had at least six months of follow-up or had
disease progression, and there was one patient death unrelated to
study treatment.
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.
Patients were enrolled and dosed in either the dose-escalation
cohort of the study, at four target 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 target dose range between 150-450 x 106 CAR+
T cells.
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.
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 by researching cerebral adrenoleukodystrophy, sickle cell
disease, transfusion-dependent 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.
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 in the development of bb2121;
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, or that marketing approval will be granted. 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 and includes risk factors related to the
proposed transaction between Bristol-Myers Squibb and Celgene, such
as, but not limited to, the risks that: Celgene’s management’s time
and attention is diverted on transaction related issues; disruption
from the transaction makes it more difficult for Celgene to
maintain business, contractual and operational relationships; and
Bristol-Myers Squibb, Celgene or the combined company is unable to
retain key personnel. 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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For
Celgene:Investors:+1-908-673-9628ir@celgene.comorMedia:+1-908-673-2275media@celgene.comFor
bluebird bioInvestors:Elizabeth Pingpank,
617-914-8736epingpank@bluebirdbio.comorMedia:Catherine Falcetti,
617-583-3411cfalcetti@bluebirdbio.com
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