Oral presentation to include data on 47
patients through five years of follow-up (median 35.5 months, range
0.3-61 months)
Endpoints of sVOE-CR and VOE-CR achieved in 94%
(32/34) and 88% (30/34) of evaluable patients respectively
100% of adolescents (10/10) experienced
complete resolution of VOEs and sVOEs, providing evidence of
potential benefit for this population
Impact on hemolysis markers and health-related
quality of life measures further support potential therapeutic
benefits
bluebird bio, Inc. (NASDAQ: BLUE) (“bluebird bio” or “bluebird”)
today announced new and updated efficacy, safety and health-related
quality of life (HRQoL) data from the Phase 1/2 HGB-206 Group C and
Phase 3 HGB-210 studies of lovotibeglogene autotemcel (lovo-cel)
gene therapy for sickle cell disease through five years of
follow-up (median 35.5 months, range 0.3-61 months). Data were
highlighted in a press briefing at the 65th American Society of
Hematology (ASH) Annual Meeting & Exposition and will be
presented in an oral presentation on Monday, December 11, 2023 at
4:30 p.m. Pacific Time.
“Years of long-term follow-up continue to suggest that lovo-cel
has the potential to address the underlying cause of sickle cell
disease and provide robust clinical benefits for patients,” said
Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio.
“The data presented at ASH give us confidence that these results
can be sustained over time and may translate to meaningful and
lasting impact on quality of life for people living with sickle
cell disease who need and deserve new treatment options.”
The analysis presented at ASH focused on 47 people living with
sickle cell disease who received lovo-cel in the HGB-206 Group C
and HGB-210 studies following enhancements to the treatment process
and manufacturing protocols. Over 85% of patients required ≤2
mobilization cycles prior to infusion. As of the February 13, 2023
cutoff date, all patients had stable production of anti-sickling
adult hemoglobin after infusion through last follow-up (median
>40% HbAT87Q), and vaso-occlusive events (VOEs) and severe
vaso-occlusive events (sVOEs) were eliminated or significantly
reduced in all patients, further suggesting that lovo-cel has shown
a durable impact on the underlying cause of sickle cell disease.
The majority of adverse events in treated patients were attributed
to underlying sickle cell disease or conditioning with
busulfan.
Lovo-cel is the most deeply studied gene therapy in development
for sickle cell disease, with the most patients treated and longest
follow-up in the field. As of February 13, 2023, 59 patients were
treated across the entire clinical development program with
follow-up beyond 8 years in the earliest treated patients.
The therapy was approved on December 8, 2023 by the U.S. Food
and Drug Administration and is currently marketed as LYFGENIA in
the U.S.
Updated efficacy data continue to support transformational
impact on VOE burden
In the studies, VOEs are defined as episodes of acute pain with
no medically determined cause other than a vaso-occlusion, lasting
more than two hours and severe enough to require care at a medical
facility. This includes acute chest syndrome requiring oxygen
treatment and/or blood transfusion, acute hepatic sequestration,
acute priapism lasting 2 hours and requiring care at a medical
facility and acute splenic sequestration. sVOEs require a 24-hour
hospital stay or emergency room visit, or at least two visits to a
hospital or emergency room over a 72-hour period, with both visits
requiring intravenous treatment; all VOEs of priapism are also
considered sVOEs.
As of February 13, 2023, 34 of the 47 patients treated in
HGB-206 Group C and HGB-210 were evaluable for the primary and
secondary endpoints of complete resolution of VOEs and sVOEs with a
median follow-up 36.3 months (12.1, 61).
- 32/34 patients (94%) experienced complete resolution of sVOEs,
maintained for a median (min, max) of 35.8 months (20.2, 61).
- 30/34 patients (88.2%) experienced complete resolution of all
VOEs, maintained for a median (min, max) of 35.8 months (20.2,
61).
- Patients who experienced VOEs at any time post-treatment
through long-term follow-up (n=8) experienced significant reduction
in VOE frequency and severity compared to before treatment.
- All 8 patients experienced a reduction in VOEs of at least
50%.
- Hospital days and admissions were reduced by as much as 100%
(annualized median hospital days reduced from 15.75 (3.5, 136)
pre-treatment to 2.20 (0.0, 25.4); (annualized median reduction in
hospital days was 85.5% (31.7%, 100%).
- Results of a sub-analysis of data from adolescent patients,
presented for the first time, showed complete resolution of VOEs
and sVOEs in 10/10 (100%) of patients during the 6-18 month
enrollment period.
“These new data provide further evidence that lovo-cel can
provide significant improvements in quality of life for people
living with sickle cell disease and that the effects are durable
for at least five years,” said Julie Kanter, M.D., a lovo-cel
investigator and director of the University of Alabama Birmingham
Adult Sickle Cell Clinic and associate professor in the Division of
Hematology and Oncology. “We see meaningful changes in hemoglobin,
excellent production of anti-sickling hemoglobin, and improvement
in all markers of hemolysis which further reinforces the clinical
effects of lovo-cel. This one-time, transformative therapy has the
potential to target the underlying cause of the disease and reduce
both pain and fatigue—outcomes that matter to people living with
sickle cell disease and their families. These findings support the
positive impact of lovo-cel on the biology of sickle cell disease
and on patients’ clinical outcomes and quality of life.”
Clinical outcomes were further supported by improvements in
total hemoglobin and markers of hemolysis
Red blood cells normally break down in the body through a
naturally occurring process called hemolysis. In sickle cell
disease, hemolysis happens too quickly due to the fragility of
sickled red blood cells, resulting in hemolytic anemia. With the
exception of patients with alpha-thalassemia trait, all patients
had improvement in total hemoglobin and markers of hemolysis;
improvements were sustained through last follow-up. As of the
February 13, 2023 cut-off date:
- Following engraftment, non‑transfused total Hb and %Hb
fractions stabilized by approximately 6 months after lovo-cel
infusion.
- Median percent of gene-therapy derived anti-sickling adult
hemoglobin (HbAT87Q) was maintained generally at >40% of
non-transfused total Hb throughout follow-up.
- From six months post-infusion through the last visit, several
indicators of the health of red blood cells suggest that treatment
with lovo-cel improved biological markers for sickle cell disease
to normal or near-normal levels. Lactate dehydrogenase and indirect
bilirubin levels normalized and reticulocyte counts approached
normal levels.
The majority of patients experienced sustained improvements
in key domains of health-related quality of life measures
The burden of sickle cell disease impacts every aspect of
patients' lives. Health-related quality of life (HRQoL) findings in
patients treated in HGB-206 Group C were generated using the
Patient Reported Outcomes Measurement Information System 57
(PROMIS-57), a validated instrument in sickle cell disease.
Improvements in key domains including pain interference, pain
intensity, and fatigue were demonstrated, showing statistically
significant improvements as early as month six which were sustained
up to 36 months for pain intensity and 48 months for pain
interference and fatigue. These findings provide a broader
understanding of the potential impact to daily life over time
following treatment with lovo-cel.
Safety results summary
The majority of adverse events in patients treated in HGB-206
Group C and HGB-210 were attributed to underlying sickle cell
disease or conditioning with busulfan. Nonserious adverse events
related to lovo-cel included infusion reactions (abdominal
discomfort, decreased diastolic blood pressure, and nasal
congestion) each in one patient (2.1% each). Serious adverse events
related to lovo-cel were reported in two patients with comorbid
alpha-thalassemia trait and they included two SAEs each of Anemia
(4.3%) and 1 SAE of Myelodysplastic syndrome (2.1%), the diagnosis
of which remains under evaluation. One patient died due to sudden
cardiac death which was deemed unrelated to lovo-cel.
As previously reported, cases of acute myeloid leukemia were
observed in two patients from the HGB-206 Group A cohort who were
treated with an earlier version of the therapy prior to
enhancements to the treatment and manufacturing processes. Both
patients died due to aforementioned leukemia.
No graft failure, replication-competent lentivirus or
vector-mediated insertional oncogenesis was observed across the
entire clinical development program.
About sickle cell disease
Sickle cell disease is a complex and progressive genetic disease
associated with debilitating and unpredictable pain crises, anemia,
irreversible damage to vital organs, and early death. In SCD, high
concentrations of sickle hemoglobin (HbS) in red blood cells (RBCs)
cause RBCs to become sickled, sticky, and rigid with a shorter life
span, which manifests acutely as hemolytic anemia, vasculopathy,
and vaso-occlusion. Pain onset can be sudden and unpredictable,
often requiring hospitalization. Fifty to sixty percent of adults
with SCD have end organ damage, with 24 percent experiencing damage
in multiple organs, and one in four patients have a stroke by the
age of 45. The impact of SCD is pervasive and affects every aspect
of life for patients and their families and caregivers – from
missed work and school, decreased quality of life and mental
health, and ability to complete daily tasks. In the U.S., there are
approximately 100,000 people living with SCD, and the median age of
death is 45 years of age.
About LYFGENIA™ (lovotibeglogene autotemcel) or
lovo-cel
LYFGENIA is a one-time ex-vivo lentiviral vector gene therapy
approved for the treatment of patients 12 years of age or older
with sickle cell disease and a history of vaso-occlusive events
(VOEs). LYFGENIA works by adding a functional β-globin gene to
patients’ own hematopoietic (blood) stem cells (HSCs). Durable
production of adult hemoglobin with anti-sickling properties
(HbAT87Q) is possible following successful engraftment. HbAT87Q has
a similar oxygen-binding affinity to wild-type HbA, limits sickling
of red blood cells and has the potential to reduce and VOEs.
The Phase 1/2 HGB-206 study of LYFGENIA is ongoing with
enrollment and treatment complete; and the Phase 3 HGB-210 study
evaluating LYFGENIA is ongoing. bluebird bio is also conducting a
long-term safety and efficacy follow-up study (LTF-307) for
patients with sickle cell disease who have been treated with
LYFGENIA in bluebird bio-sponsored clinical studies.
Indication
LYFGENIA is indicated for the treatment of patients 12 years of
age or older with sickle cell disease and a history of
vaso-occlusive events (VOEs).
Limitations of Use
Following treatment with LYFGENIA, patients with α-thalassemia
trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia
that may require chronic red blood cell transfusions. LYFGENIA has
not been studied in patients with more than two α-globin gene
deletions.
Important Safety Information
Boxed WARNING: HEMATOLOGIC MALIGNANCY
Hematologic malignancy has occurred in patients treated with
LYFGENIA. Monitor patients closely for evidence of
malignancy through complete blood counts at least every 6 months
and through integration site analysis at Months 6, 12, and
as warranted.
Hematologic Malignancy
Hematologic malignancy has occurred in patients treated with
LYFGENIA (Study 1, Group A). At the time of initial product
approval, two patients treated with an earlier version of LYFGENIA
using a different manufacturing process and transplant procedure
(Study 1, Group A) developed acute myeloid leukemia (AML). One
patient with α-thalassemia trait (Study 1, Group C) has been
diagnosed with myelodysplastic syndrome (MDS).
The additional hematopoietic stress associated with
mobilization, conditioning, and infusion of LYFGENIA, including the
need to regenerate the hematopoietic system, may increase the risk
of a hematologic malignancy. Patients with sickle cell disease have
an increased risk of hematologic malignancy as compared to the
general population.
Patients treated with LYFGENIA may develop hematologic
malignancies and should have lifelong monitoring. Monitor for
hematologic malignancies with a complete blood count (with
differential) at least every 6 months for at least 15 years after
treatment with LYFGENIA, 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.
Post-Marketing Long Term Follow-Up
Study: Patients who intend to receive treatment with
LYFGENIA are encouraged to enroll in the study, as available, to
assess the long-term safety of LYFGENIA and the risk of
malignancies occurring after treatment with LYFGENIA by calling
bluebird bio at 1-833-999-6378. The study includes monitoring (at
pre-specified intervals) for clonal expansion.
Delayed Platelet Engraftment
Delayed platelet engraftment has been observed with LYFGENIA.
Bleeding risk is increased prior to platelet engraftment and may
continue after engraftment in patients with prolonged
thrombocytopenia. Two patients (4%) required more than 100 days
post treatment with LYFGENIA to achieve platelet engraftment.
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.
Neutrophil Engraftment Failure
There is a potential risk of neutrophil engraftment failure
after treatment with LYFGENIA. Neutrophil engraftment failure is
defined as failure to achieve three consecutive absolute neutrophil
counts (ANC) ≥ 0.5 × 109 cells/L obtained on different days by Day
43 after infusion of LYFGENIA. Monitor neutrophil counts until
engraftment has been achieved. If neutrophil engraftment failure
occurs in a patient treated with LYFGENIA, provide rescue treatment
with the back-up collection of CD34+ cells.
Insertional Oncogenesis
There is a potential risk of lentiviral vector-mediated
insertional oncogenesis after treatment with LYFGENIA.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of LYFGENIA. The
dimethyl sulfoxide (DMSO) or dextran 40 in LYFGENIA may cause
hypersensitivity reactions, including anaphylaxis.
Anti-retroviral Use
Patients should not take prophylactic HIV anti-retroviral
medications for at least one month prior to mobilization and until
all cycles of apheresis are completed. There are some long-acting
anti-retroviral medications that may require a longer duration of
discontinuation for elimination of the medication. If a patient is
taking anti-retrovirals for HIV prophylaxis, confirm a negative
test for HIV before beginning mobilization and apheresis of CD34+
cells.
Hydroxyurea Use
Patients should not take hydroxyurea for at least 2 months prior
to mobilization and until all cycles of apheresis are completed. If
hydroxyurea is administered between mobilization and conditioning,
discontinue 2 days prior to initiation of conditioning.
Iron Chelation
Drug-drug interactions between iron chelators and the
mobilization process and myeloablative conditioning agent must be
considered. Iron chelators should be discontinued at least 7 days
prior to initiation of mobilization or conditioning. Do not
administer myelosuppressive iron chelators (e.g., deferiprone) for
6 months post-treatment with LYFGENIA. Non-myelosuppressive iron
chelation should be restarted no sooner than 3 months after
LYFGENIA infusion. Phlebotomy can be used in lieu of iron
chelation, when appropriate.
Interference with PCR-based Testing
Patients who have received LYFGENIA are likely to test positive
by polymerase chain reaction (PCR) assays for HIV due to integrated
BB305 LVV proviral DNA, resulting in a possible false-positive PCR
assay test result for HIV. Therefore, patients who have received
LYFGENIA should not be screened for HIV infection using a PCR-based
assay.
Adverse Reactions
The most common adverse reactions ≥ Grade 3 (incidence ≥ 20%)
were stomatitis, thrombocytopenia, neutropenia, febrile
neutropenia, anemia, and leukopenia.
Three patients died during LYFGENIA clinical trials; one from
sudden cardiac death due to underlying disease and two from acute
myeloid leukemia who were treated with an earlier version of
LYFGENIA using a different manufacturing process and transplant
procedure (Study 1, Group A).
Pregnancy/Lactation
Advise patients of the risks associated with myeloablative
conditioning agents, including on pregnancy and fertility.
LYFGENIA should not be administered to women who are pregnant,
and pregnancy after LYFGENIA infusion should be discussed with the
treating physician.
LYFGENIA is not recommended for women who are breastfeeding, and
breastfeeding after LYFGENIA 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 LYFGENIA 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 LYFGENIA.
Advise patients of the options for fertility preservation.
Please see full Prescribing Information for LYFGENIA
including Boxed WARNING and Medication Guide.
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give
patients and their families more bluebird days.
Founded in 2010, bluebird has been setting the standard for gene
therapy for more than a decade—first as a scientific pioneer and
now as a commercial leader. bluebird has an unrivaled track record
in bringing the promise of gene therapy out of clinical studies and
into the real-world setting, having secured FDA approvals for three
therapies in under two years. Today, we are proving and scaling the
commercial model for gene therapy and delivering innovative
solutions for access to patients, providers, and payers.
With a dedicated focus on severe genetic diseases, bluebird has
the largest and deepest ex-vivo gene therapy data set in the field,
with industry-leading programs for sickle cell disease,
β-thalassemia and cerebral adrenoleukodystrophy. 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.
bluebird continues to forge new paths as a standalone commercial
gene therapy company, 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.
LYFGENIA and bluebird bio are trademarks of bluebird bio,
Inc.
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 as
statements regarding the therapeutic potential of lovo-cel,
including with respect to its durable, one-time transformative, and
potentially curative benefits and its impact on quality of life for
patients. Such forward-looking statements are based on historical
performance and current expectations and projections about
bluebird’s 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 bluebird’s control and could cause bluebird’s 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 for the year ended December 31, 2022, as updated by its
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:
delays and challenges in bluebird’s commercialization and
manufacturing of its products; the internal and external costs
required for bluebird’s ongoing and planned activities, and the
resulting impact on expense and use of cash, has been, and may in
the future be, higher than expected which has caused bluebird, and
may in the future cause bluebird to use cash more quickly than it
expects or change or curtail some of its plans or both; substantial
doubt exists regarding bluebird’s ability to continue as a going
concern; bluebird’s expectations as to expenses, cash usage and
cash needs may prove not to be correct for other reasons such as
changes in plans or actual events being different than its
assumptions; the risk that the efficacy and safety results from
bluebird’s prior and ongoing clinical trials will not continue or
be seen in the commercial context; the risk of insertional
oncogenic or other safety events associated with lentiviral vector,
drug product, or myeloablation; and the risk that lovo-cel will not
be successfully 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231209650405/en/
Investors: Courtney O’Leary, 978-621-7347
coleary@bluebirdbio.com
Media: Jess Rowlands, 518-598-3168
jess.rowlands@bluebirdbio.com
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