ZYNTEGLO offers potentially curative benefit
across ages and genotypes, through the achievement of durable
transfusion independence and normal or near normal total hemoglobin
levels
Management team to host conference call
Thursday, August 18 at 8:00 am ET
bluebird bio, Inc. (Nasdaq: BLUE) today announced the U.S. Food
and Drug Administration (FDA) has approved ZYNTEGLO® (betibeglogene
autotemcel), also known as beti-cel, a one-time gene therapy
custom-designed to treat the underlying genetic cause of
beta‑thalassemia in adult and pediatric patients who require
regular red blood cell (RBC) transfusions.
“The FDA approval of ZYNTEGLO offers people with
beta-thalassemia the possibility of freedom from burdensome regular
red blood cell transfusions and iron chelation, and unlocks new
possibilities in their daily lives,” said Andrew Obenshain, chief
executive officer, bluebird bio. “After more than a decade of
research and clinical development, and through the perseverance of
clinicians, patients, and their families, the approval of ZYNTEGLO
marks a watershed moment for the field of gene therapy. As the
first ex-vivo lentiviral vector gene therapy approved in the U.S.
for the treatment of people with beta-thalassemia, we are ushering
in a new era in which gene therapy has the potential to transform
existing treatment paradigms for diseases that currently carry a
lifelong burden of care.”
Beta-thalassemia is a rare, genetic blood disease caused by
mutations in the beta-globin gene and characterized by
significantly reduced or absent adult hemoglobin production.
Patients with the most severe form, sometimes called
transfusion-dependent beta-thalassemia or beta-thalassemia major,
experience severe anemia and lifelong dependence on regular red
blood cell transfusions, a lengthy process that patients typically
undergo every 2-5 weeks. Despite advances in treatment and improved
transfusion techniques, transfusions only temporarily address
symptoms of anemia and people with beta‑thalassemia who require
regular transfusions have an increased risk for morbidity and
mortality due to complications from treatment-related iron
overload. Data from the Cooley’s Anemia Foundation indicate that
the median age of death of patients with transfusion-dependent
beta‑thalassemia in the U.S. who died during the last decade was
just 37 years. bluebird estimates that there are approximately
1,300-1,500 individuals with transfusion-dependent beta-thalassemia
in the U.S.
“Transfusion-dependent beta-thalassemia is associated with an
intense treatment burden and significant health risks related to
regular red blood transfusions and iron management,” said Alexis A.
Thompson, MD, MPH, Chief of the Division of Hematology, Children's
Hospital of Philadelphia. “As a clinician and an investigator in
the ZYNTEGLO clinical development program, I celebrate the
therapeutic potential of this treatment for patients and its
implications for the field of gene therapy, all made possible
through the incredible courage of patients and families who
participated in the clinical trials.”
“The Cooley’s Anemia Foundation applauds the FDA’s approval of
ZYNTEGLO for people with beta‑thalassemia who require regular red
blood cell transfusions. The availability of a one-time gene
therapy which offers the possibility of transfusion independence
opens up new and exciting opportunities for those who are medically
eligible to receive this treatment option,” said Craig Butler,
National Executive Director, Cooley’s Anemia Foundation. “While
advances in treatment have been of enormous benefit to those with
beta-thalassemia, a potentially curative therapy may offer a true
life-changing experience.”
The approval of ZYNTEGLO is the culmination of nearly 10 years
of clinical research of gene therapy in patients with
transfusion-dependent beta-thalassemia. ZYNTEGLO works by adding
functional copies of a modified form of the beta-globin gene
(βA-T87Q-globin gene) into a patient’s own hematopoietic (blood)
stem cells (HSCs) to allow them to make normal to near normal
levels of total hemoglobin without regular RBC transfusions. The
functional beta-globin gene is added into a patient’s cells outside
of the body (ex-vivo), and then infused into the patient. Though
ZYNTEGLO is designed to be administered to the patient once, the
treatment process is comprised of several steps that may take place
over the course of several months.
Due to the complex nature of gene therapy, ZYNTEGLO will be
available exclusively at Qualified Treatment Centers (QTCs) which
are carefully selected based on their expertise in relevant areas
such as stem cell transplantation, cell and gene therapy, and
beta-thalassemia; and receive specialized training to administer
ZYNTEGLO. Information on bluebird’s QTC network, as well as
personalized support focused on the needs of each patient
throughout their treatment journey and information on insurance
coverage and access will be available through bluebird’s patient
support program, my bluebird support. Patients can call
833-888-NEST (833-888-6378) for more information, and additional
details will be available at mybluebirdsupport.com in the coming
days.
ZYNTEGLO was reviewed under Priority Review, and the Company
received a Priority Review voucher upon approval. ZYNTEGLO was
previously granted Orphan Drug designation and Breakthrough Therapy
designation.
Clinical Data Supporting Approval of ZYNTEGLO
bluebird bio has the longest and most robust clinical program in
transfusion-dependent beta‑thalassemia (TDT) in the field of gene
therapy. The approval of ZYNTEGLO is based on data from bluebird
bio’s Phase 3 studies HGB-207 (Northstar-2) and HGB-212
(Northstar-3), and the long-term follow-up study LTF-303.
The single-arm, open-label, 24-month Phase 3 studies of ZYNTEGLO
included 41 patients aged 4 to 34 years with both non-β0/β0 and
β0/β0 genotypes, with longest follow up out to 4 years. Eighty-nine
percent (32/36) of evaluable patients across ages and genotypes
achieved transfusion independence (TI), which is defined as no
longer needing red blood cell transfusions for at least 12 months
while maintaining a weighted average total hemoglobin of at least 9
g/dL. Results in these patients were durable as of last
follow-up.
The most common non-laboratory adverse reactions (≥20%) were
mucositis, febrile neutropenia, vomiting, pyrexia, alopecia,
epistaxis, abdominal pain, musculoskeletal pain, cough, headache,
diarrhea, rash, constipation, nausea, decreased appetite,
pigmentation disorder, and pruritus. The most common Grade 3 or 4
laboratory abnormalities (>50%) include neutropenia,
thrombocytopenia, leukopenia, anemia, and lymphopenia.
Enrollment is complete and all patients have been treated in the
Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies
evaluating ZYNTEGLO. Follow-up in HGB-212 is ongoing. bluebird bio
is also conducting a long-term follow-up study, LTF-303, to monitor
safety and efficacy for patients with TDT who have participated in
bluebird bio-sponsored clinical studies of lentiviral vector (LVV)
gene therapy through 15 years post-treatment.
Across all studies, all patients who achieved transfusion
independence have remained transfusion-free.
Investor Conference Call Information
bluebird bio will host a call for analysts and investors on
Thursday, August 18, 2022, at 8:00 am ET. Please note that there is
a new process to access the call via telephone. To register and
receive a dial in number and unique PIN to access the live
conference call, please follow this link
https://register.vevent.com/register/BIf8d187c3d45b4919a79fdc98742f39da
to register online.
The live webcast of the call and slide deck may be accessed by
visiting the “Events & Presentations” page within the Investors
& Media section of the bluebird website at
http://investor.bluebirdbio.com. A replay of the webcast will be
available on the bluebird website for 90 days following the
event.
About ZYNTEGLO® (betibeglogene autotemcel) or
beti-cel
ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy
approved for the treatment of beta-thalassemia in adult and
pediatric patients who require regular red blood cell (RBC)
transfusions. ZYNTEGLO works by adding functional copies of a
modified form of the beta-globin gene (βA-T87Q-globin gene) into a
patient’s own hematopoietic (blood) stem cells to enable the
production of a modified functional adult hemoglobin (HbAT87Q).
Once a patient has the βA-T87Q-globin gene, they have the potential
to increase ZYNTEGLO-derived adult hemoglobin (HbAT87Q) and total
hemoglobin to normal or near normal levels that can eliminate the
need for regular RBC transfusions.
Indication
ZYNTEGLO is indicated for the treatment of adult and pediatric
patients with beta-thalassemia who require regular red blood cell
(RBC) transfusions.
Important Safety Information
Delayed Platelet Engraftment
Delayed platelet engraftment has been observed with ZYNTEGLO
treatment. Bleeding risk is increased prior to platelet engraftment
and may continue after engraftment in patients with prolonged
thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets
on or after Day 100.
Patients should be made aware of the risk of bleeding until
platelet recovery has been achieved. Monitor patients for
thrombocytopenia and bleeding according to standard guidelines.
Conduct frequent platelet counts until platelet engraftment and
platelet recovery are achieved. Perform blood cell count
determination and other appropriate testing whenever clinical
symptoms suggestive of bleeding arise.
Risk of Neutrophil Engraftment Failure
There is a potential risk of neutrophil engraftment failure
after treatment with ZYNTEGLO. Neutrophil engraftment failure is
defined as failure to achieve three consecutive absolute neutrophil
counts (ANC) ≥ 500 cells/microliter obtained on different days by
Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until
engraftment has been achieved. If neutrophil engraftment failure
occurs in a patient treated with ZYNTEGLO, provide rescue treatment
with the back-up collection of CD34+ cells.
Risk of Insertional Oncogenesis
There is a potential risk of LVV mediated insertional
oncogenesis after treatment with ZYNTEGLO.
Patients treated with ZYNTEGLO may develop hematologic
malignancies and should be monitored lifelong. Monitor for
hematologic malignancies with a complete blood count (with
differential) at Month 6 and Month 12 and then at least annually
for at least 15 years after treatment with ZYNTEGLO, and
integration site analysis at Months 6, 12, and as warranted.
In the event that a malignancy occurs, contact bluebird bio at 1
833-999-6378 for reporting and to obtain instructions on collection
of samples for testing.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of ZYNTEGLO. The
dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity
reactions, including anaphylaxis.
Anti-retroviral and Hydroxyurea Use
Patients should not take prophylactic HIV anti-retroviral
medications or hydroxyurea for at least one month prior to
mobilization, or for the expected duration for elimination of the
medications, and until all cycles of apheresis are completed. If a
patient requires anti-retrovirals for HIV prophylaxis, then confirm
a negative test for HIV before beginning mobilization and apheresis
of CD34+ cells.
Interference with Serology Testing
Patients who have received ZYNTEGLO are likely to test positive
by polymerase chain reaction (PCR) assays for HIV due to integrated
BB305 LVV proviral DNA, resulting in a false-positive test for HIV.
Therefore, patients who have received ZYNTEGLO should not be
screened for HIV infection using a PCR‑based assay.
Adverse Reactions
The most common non-laboratory adverse reactions (≥20%) were
mucositis, febrile neutropenia, vomiting, pyrexia, alopecia,
epistaxis, abdominal pain, musculoskeletal pain, cough, headache,
diarrhea, rash, constipation, nausea, decreased appetite,
pigmentation disorder, and pruritus. The most common Grade 3 or 4
laboratory abnormalities (>50%) include neutropenia,
thrombocytopenia, leukopenia, anemia, and lymphopenia.
Drug Interactions
Drug-drug interactions between iron chelators and the
myeloablative conditioning agent must be considered. Iron chelators
should be discontinued at least 7 days prior to initiation of
conditioning. The prescribing information for the iron chelator(s)
and the myeloablative conditioning agent should be consulted for
the recommendations regarding co-administration with CYP3A
substrates.
Some iron chelators are myelosuppressive. After ZYNTEGLO
infusion, avoid use of these iron chelators for 6 months. If iron
chelation is needed, consider administration of
non-myelosuppressive iron chelators. Phlebotomy can be used in lieu
of iron chelation, when appropriate.
Pregnancy/Lactation
Advise patients of the risks associated with conditioning
agents, including on pregnancy and fertility.
ZYNTEGLO should not be administered to women who are pregnant,
and pregnancy after ZYNTEGLO infusion should be discussed with the
treating physician.
ZYNTEGLO is not recommended for women who are breastfeeding, and
breastfeeding after ZYNTEGLO infusion should be discussed with the
treating physician.
Females and Males of Reproductive Potential
A negative serum pregnancy test must be confirmed prior to the
start of mobilization and re-confirmed prior to conditioning
procedures and before ZYNTEGLO administration.
Women of childbearing potential and men capable of fathering a
child should use an effective method of contraception (intra
uterine device or combination of hormonal and barrier
contraception) from start of mobilization through at least 6 months
after administration of ZYNTEGLO.
Advise patients of the option to cryopreserve semen or ova
before treatment if appropriate.
Please see full Prescribing Information for ZYNTEGLO.
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give
patients and their families more bluebird days. With a dedicated
focus on severe genetic diseases, bluebird has industry-leading
clinical and research programs for sickle cell disease,
beta-thalassemia and cerebral adrenoleukodystrophy and is advancing
research to apply new technologies to these and other diseases. We
custom design each of our therapies to address the underlying cause
of disease and have developed in-depth and effective analytical
methods to understand the safety of our lentiviral vector
technologies and drive the field of gene therapy forward.
Founded in 2010, bluebird has the largest and deepest ex-vivo
gene therapy data set in the world—setting the standard for
industry. Today, bluebird continues to forge new paths, combining
our real‑world experience with a deep commitment to patient
communities and a people-centric culture that attracts and grows a
diverse flock of dedicated birds.
For more information, visit bluebirdbio.com or follow us
on social media at @bluebirdbio, LinkedIn,
Instagram and YouTube.
ZYNTEGLO and bluebird bio are trademarks of bluebird bio,
Inc.
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. 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 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 goals, plans and objectives to differ materially from
those expressed in, or implied by, the statements. 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, 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. These risks and uncertainties include, but are not
limited to: the risk that the efficacy and safety results from our
prior and ongoing clinical trials will not continue or be seen in
the commercial treatment context; the risk that additional
insertional oncogenic or other safety events associated with
lentiviral vector, drug product, or myeloablation will be
discovered or reported over time; the risk that we may not be able
to obtain adequate price and reimbursement for any approved
products; the risk that we may encounter delays in the initiation
of our commercial operations in the United States; and the risk
that any one or more of our product candidates will not be
successfully developed, approved by the FDA or commercialized. 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20220817005667/en/
Investors: Courtney O’Leary, 978-621-7347
coleary@bluebirdbio.com Media: Jess Rowlands,
857-299-6103 jess.rowlands@bluebirdbio.com
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