Celgene and bluebird bio happy with expansion and persistence ofthe CAR T-cells seen in Phase 1 Study

Celgene and bluebird bio happy with expansion and persistence ofthe CAR T-cells seen in Phase 1 Study

May 2, 2019 Off By BusinessWire

SUMMIT, N.J. & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Celgene Corporation and bluebird in New England Journal of Medicine (NEJM)published the manuscript, “Anti-BCMA CAR T Cell Therapy bb2121 in Relapsed/Refractory Multiple Myeloma”, said the 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,

“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

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: @CelgenePinterestLinkedInFacebook 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: @bluebirdbioLinkedInInstagram 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
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their respective control.


For Celgene:
[email protected]
[email protected]

bluebird bio
Elizabeth Pingpank, 617-914-8736
[email protected]
Falcetti, 617-583-3411
[email protected]