bb21217 early safety profile consistent with
CAR T platform therapies
83 percent objective response rate in 12
heavily pretreated multiple myeloma patients at first dose level
studied
Higher dose of bb21217 being assessed in the
ongoing Phase 1 study
bluebird bio, Inc. (Nasdaq:BLUE) and Celgene Corporation
(NASDAQ:CELG) announced initial data from the ongoing Phase 1
clinical study of bb21217 (CRB-402), an investigational
next-generation anti-BCMA CAR T cell therapy being studied in
patients with relapsed/refractory multiple myeloma. The data were
presented by Nina Shah, M.D., University of California, San
Francisco, as an oral presentation at the 60th Annual Meeting of
the American Society of Hematology (ASH).
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20181202005065/en/
bb21217 is an investigational anti-BCMA CAR T cell therapy that
uses the bb2121 chimeric antigen receptor (CAR) molecule with a
manufacturing process designed to improve CAR T cell functional
persistence. bb21217 has exhibited improved functional persistence
and increased anti-tumor activity in preclinical animal
studies.
“Anti-BCMA CAR T therapy with bb2121 has shown clinical
responses in a substantial proportion of patients with
relapsed/refractory multiple myeloma. With the bb21217 program we
are pursuing an approach intended to improve the in vivo
persistence of functional CAR T cells with the hope that this
provides a more durable benefit for patients,” said David Davidson,
M.D., chief medical officer, bluebird bio. “The safety results and
promising response rate in the initial dose cohort, as well as the
observation of detectable CAR T cells in the first three patients
with follow up to the month 6 study visit and beyond, support
advancing to a higher dose to further characterize the potential of
bb21217 as a treatment option for patients with relapsed/refractory
multiple myeloma.”
“The initial results of bb21217 are encouraging in terms of the
adverse event profile, as well as the instances of ongoing, deep
responses shown in these heavily pre-treated patients,” said Alise
Reicin, M.D., President, Global Clinical Development for Celgene.
“We look forward to further results from this next-generation agent
in this area of continued medical need.”
bb21217 is being evaluated in the ongoing dose escalation part
of the Phase 1 CRB-402 study in adults with relapsed/refractory
multiple myeloma who have received at least three prior treatments,
including a proteasome inhibitor and immunomodulatory agent (or are
double refractory).
“Patients with multiple myeloma often undergo multiple cycles of
treatment because there is currently no known cure for this
aggressive cancer,” said Nina Shah, M.D., University of California,
San Francisco, San Francisco, Calif. “The early clinical data from
this Phase 1 study show manageable safety findings, and most
patients in this initial group achieved an objective response.
Future study is needed to assess durability of response at the
current dose, as well as safety and activity at higher doses of
bb21217.”
Patients included in these preliminary Phase 1 results (n=12)
had a median age of 63 years (min; max: 44 – 69 years). They had
received a median of seven prior lines of therapy (min; max: 4 – 17
lines) and 83 percent of patients received a prior autologous stem
cell transplant. Fifty-eight percent (n=7) of patients had
high-risk cytogenetics.
All treated patients received a dose of 150 x 106 CAR+ T cells.
The median follow-up after bb21217 infusion was 26 weeks (min; max:
4 – 51 weeks). The primary endpoint is safety measured by frequency
of adverse events (AEs), dose limiting toxicity (DLT) and changes
in laboratory results. Secondary endpoints include disease specific
response criteria based on the International Myeloma Working Group
(IMWG) Uniform Response Criteria for Multiple Myeloma.
Safety Results
The safety results, reported as of the data extract of October
18, 2018, were manageable and consistent with known toxicities of
CAR T therapies.
Eight of the 12 patients (67 percent) treated with bb21217
developed cytokine release syndrome (CRS); four Grade 1, three
Grade 2, one Grade 3 case and no Grade 4 cases. Additionally, three
of the 12 patients (25 percent) experienced neurotoxicity,
including one Grade 1, one Grade 2 and one Grade 4 case. All CRS
and neurotoxicity events resolved and no deaths occurred on study.
Following the Grade 4 neurotoxicity event, patients were divided
into two groups based on tumor burden and dosing continued at 150 x
106 CAR+ T cells for a total of 12 subjects treated at this dose
level.
Efficacy Results
Of the 12 patients who received treatment with bb21217, 83
percent (n=10) achieved an objective clinical response by IMWG
criteria. As of the data extract, responses are ongoing in nine of
10 patients, including three with a complete response (CR) or
stringent complete response (sCR), two with a very good partial
response (VGPR) and four with a partial response (PR).
Evidence of myeloma in the bone marrow, known as minimal
residual disease (MRD), was undetectable at a minimum of two time
points, by next-generation sequencing at a sensitivity level of
10-5 or better in all responders who had evaluable bone marrow
samples (n=4) with some as early as day 15.
CAR+ T cell expansion was observed during the first 30 days
following treatment in all evaluable patients (n=11) with anti-BCMA
CAR+T cells showing sustained persistence in all patients (3/3)
with six or more months of follow-up.
The ongoing Phase 1 CRB-402 study is assessing a higher dose of
300 x106 CAR+ T cells in both high and low tumor burden
cohorts.
About bb21217
bb2121 and bb21217 are bluebird bio’s lead investigational
anti-BCMA CAR T therapies being developed in collaboration with
Celgene.
Chimeric antigen receptors (CAR) are receptor proteins that have
been engineered to give T cells the ability to target a specific
protein. bb2121 and bb21217 are designed to recognize and kill
plasma cells, notably malignant myeloma cells, that express the B
cell maturation antigen (BCMA).
bluebird bio’s clinical development program for bb21217 includes
the ongoing Phase 1 CRB-402 two-part (dose escalation and dose
expansion), non-randomized, open label study with sites in the
United States. For more information visit: clinicaltrials.gov using
identifier NCT03274219.
bb21217 is not approved for any indication in any geography.
About Multiple Myeloma
Multiple myeloma is a cancer of certain cells in the blood,
called plasma cells. The cause of multiple myeloma is not known,
and currently there is no cure. However, there are a number of
treatment options available that can lead to remission. For some
people with multiple myeloma, remission can last many years.
Patients who have already been treated with some available
therapies but continue to have progression of their disease have
“relapsed” or “refractory” multiple myeloma, meaning their cancer
has reoccurred after they have received initial treatments.
Patients with relapsed/refractory multiple myeloma have fewer
treatment options.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy
expertise and gene editing capabilities, bluebird bio has built a
pipeline with broad potential application in severe genetic
diseases and cancer.
bluebird bio's gene therapy clinical programs include
investigational treatments for cerebral adrenoleukodystrophy,
transfusion-dependent β-thalassemia and sickle cell disease.
bluebird bio's oncology pipeline is built upon the company's
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. The
company’s lead oncology programs are anti-BCMA CAR T programs
partnered with Celgene.
bluebird bio’s discovery research programs include 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.
For more information, visit www.bluebirdbio.com.
Follow bluebird bio on social media: @bluebird bio, LinkedIn,
Instagram, YouTube.
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: Twitter, Pinterest, LinkedIn,
Facebook and YouTube.
UC Disclaimer
The information stated above was prepared by bluebird bio Inc.
and reflects solely the opinion of bluebird bio. Nothing in this
statement shall be construed to imply any support or endorsement of
bluebird bio, or any of its products, by the Regents of the
University of California, its officers, agents and employees.
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
and bb21217; the potential of bb2121 and bb21217 as therapeutic
drugs; 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. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20181202005065/en/
For bluebird bio:Investors:Elizabeth Pingpank,
617-914-8736epingpank@bluebirdbio.comorMedia:Catherine Falcetti,
617-583-3411cfalcetti@bluebirdbio.com
For
Celgene:Investors:+1-908-673-9628ir@celgene.comorMedia:+1-908-673-2275media@celgene.com
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Feb 2024 to Mar 2024
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Mar 2023 to Mar 2024