bluebird bio Receives Positive Opinion from CHMP for ZYNTEGLO™ (autologous CD34+ cells encoding βA-T87Q-globin gene) Gene Therapy for Patients 12 Years and Older with Transfusion-Dependent β-Thalassemia (TDT) Who Do Not Have β0/β0 Genotype

bluebird
bio, Inc. (Nasdaq:BLUE) announced today that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines Agency
(EMA) adopted a positive opinion recommending conditional marketing
authorization for ZYNTEGLO™ (autologous CD34+ cells encoding β
^A-T87Q-globin gene), a gene therapy for patients 12 years and
older with transfusion-dependent β-thalassemia (TDT) who do not have a β⁰/β⁰ genotype,
for whom hematopoietic stem cell (HSC) transplantation is appropriate
but a human leukocyte antigen (HLA)-matched related HSC donor is not
available. If approved, ZYNTEGLO, formerly referred to as LentiGlobin™
for TDT, will be the first gene therapy to treat TDT.

The CHMP’s positive opinion will now be reviewed by the European
Commission (EC), which has the authority to grant marketing
authorization for ZYNTEGLO in the European Union (EU). A CHMP positive
opinion is one of the final steps before the EC decides on whether to
authorize a new medicine. A final decision by the EC for ZYNTEGLO is
anticipated in the second quarter of 2019.

TDT is a severe genetic disease caused by mutations in the β-globin gene
that result in reduced or absent hemoglobin. In order to survive, people
with TDT maintain hemoglobin levels through lifelong chronic blood
transfusions. These transfusions carry the risk of progressive
multi-organ damage due to unavoidable iron overload.

“The goal of treatment with ZYNTEGLO is to enable patients with
transfusion-dependent β-thalassemia to produce hemoglobin at sufficient
levels to allow lifelong independence from blood transfusions,” said
David Davidson, M.D., chief medical officer, bluebird bio. “The positive
CHMP opinion for ZYNTEGLO is a crucial step toward providing what would
be the first one-time gene therapy for people living with TDT. We share
this achievement with the TDT community, patients and clinical
investigators whose dedication made it possible. We look forward to the
upcoming decision from the European Commission.”

“For many of my patients, living with TDT means a lifetime of chronic
blood transfusions, iron chelation therapy and supportive treatments to
manage anemia and other serious complications of this disease,” said
Professor Franco Locatelli, M.D., Ph.D., Professor of Pediatrics,
Sapienza University of Rome, Italy and Director, Department of Pediatric
Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico
Bambino Gesù, Rome, Italy. “The burden placed on these patients and
their families is significant. It extends beyond immediate health
implications to their daily lives, which are affected by the symptoms,
hospitalizations and necessary chronic care required for TDT.”

“The present management of TDT, including regular blood transfusions
every two to four weeks and daily iron chelation therapy has many
psychological and social consequences, including marginalization and
isolation. And in many patients TDT-related morbidities can lead to a
shortened life span. Therefore, it is with great anticipation and
eagerness that the international patient community has closely followed
the dynamic rejuvenation of scientific interest and research of gene
therapy in TDT over the last few years,” said Dr. Androulla Eleftheriou,
Thalassaemia International Federation Executive Director. “Thus, the
potential approval of a gene therapy brings hope that we can
dramatically change the course of this disease and the health and
quality of lives of patients with TDT.”

ZYNTEGLO adds functional copies of a modified form of the β-globin gene
(β ^A-T87Q-globin gene) into a patient’s own hematopoietic
(blood) stem cells (HSCs). This means there is no need for donor HSCs
from another person as is required for allogeneic HSC transplantation
(allo-HSCT). A patient’s HSCs are collected and removed from the body
through a process called apheresis. These HSCs are taken to a lab where
a lentiviral vector is used to insert the β ^A-T87Q-globin
gene into the patient’s HSCs. This step is called transduction. Before
their modified HSCs are returned, the patient receives chemotherapy to
prepare their bone marrow for the modified HSCs, which are returned
through an infusion. Once a patient has the β ^A-T87Q-globin
gene they have the potential to produce HbA^T87Q, which is
gene therapy- derived-hemoglobin, at levels that significantly reduce or
eliminate the need for transfusions.

“The EMA’s collaborative approach and innovative programs have been
instrumental in improving timely access of new medicines to patients
with significant unmet needs, like those who are living with TDT,” said
Anne-Virginie Eggimann, senior vice president of regulatory science at
bluebird bio.

ZYNTEGLO was reviewed under an accelerated assessment timeline as part
of the EMA’s Priority Medicines (PRIME) and Adaptive Pathways programs,
which support medicines that may offer a major therapeutic advantage
over existing treatments, or benefit patients without treatment options.

Data Supporting Clinical Profile of ZYNTEGLO

The positive CHMP opinion is supported by efficacy, safety and
durability data from the Phase 1/2 HGB-205 study and the completed Phase
1/2 Northstar (HGB-204) study as well as available data from the ongoing
Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies, and the
long-term follow-up study LTF-303.

As of September 14, 2018, data from Phase 1/2 Northstar showed that 80
percent (n=8/10) of patients who do not have a β⁰/β⁰ genotype
achieved transfusion independence, meaning they had not received a
transfusion for at least 12 months and maintained hemoglobin ≥9 g/dL.
These eight patients had maintained transfusion independence for a
median duration of 38 months (21 – 44 months) at the time of data cut
off.

In the Phase 3 Northstar-2 and Northstar-3 studies, a refined
manufacturing process was used to produce ZYNTEGLO and was intended to
further improve the clinical results observed in the Northstar study. As
of September 14, 2018, the median (min – max) total hemoglobin for
patients six months after ZYNTEGLO infusion in the Northstar-2 study
(n=10) was 11.9 (8.4, 13.3) g/dL.

Non-serious adverse events (AEs) observed during clinical trials that
were attributed to ZYNTEGLO were hot flush, dyspnoea, abdominal pain,
pain in extremities and non-cardiac chest pain. One serious adverse
event (SAE) of thrombocytopenia was considered possibly related to
ZYNTEGLO.

Additional AEs observed in clinical studies were consistent with the
known side effects of HSC and bone marrow ablation with busulfan
including SAEs of veno-occlusive disease.

ZYNTEGLO continues to be evaluated in the ongoing Phase 3 Northstar-2
and Northstar-3 studies and the long-term follow-up study LTF-303.

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.

ZYNTEGLO and LentiGlobin are trademarks of bluebird bio.

The full common name for ZYNTEGLO: A genetically modified autologous
CD34+ cell enriched population that contains hematopoietic stem cells
transduced with lentiviral vector encoding the β ^A-T87Q-globin
gene.

Forward-Looking Statements
This release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements regarding
the Company’s plans and expectations for the regulatory approval, and
commercialization for ZYNTEGLO™ (autologous CD34+ cells encoding β ^A-T87Q-globin
gene, formerly LentiGlobin™ in TDT) to treat TDT, and the potential
implications of clinical data for patients. Any forward-looking
statements are based on management’s current expectations of future
events and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those set
forth in or implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to: the risk that our MAA
submitted for ZYNTEGLO may not be approved by the European Commission
when expected, or at all; the risk that the efficacy and safety results
from our prior and ongoing clinical trials of ZYNTEGLO will not continue
or be repeated in our ongoing or planned clinical trials of ZYNTEGLO;
the risk that the current or planned clinical trials of ZYNTEGLO will be
insufficient to support regulatory submissions or marketing approval in
the US and EU; the risk that the production of HbAT87Q may not be
sustained over extended periods of time; and the risk that we may not
secure adequate pricing or reimbursement to support continued
development or commercialization of ZYNTEGLO following regulatory
approval. For a discussion of other risks and uncertainties, and other
important factors, any of which could cause our actual results to differ
from those contained in the forward-looking statements, see the section
entitled “Risk Factors” in our most recent Form 10-K, as well as
discussions of potential risks, uncertainties, and other important
factors in our subsequent filings with the Securities and Exchange
Commission. All information in this press release is as of the date of
the release, and bluebird bio undertakes no duty to update this
information unless required by law.

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