All patients who achieved transfusion
independence continue to remain transfusion free in ongoing
long-term follow-up study
87% (13/15) of pediatric patients in Phase 3
studies achieved transfusion independence with median weighted
average hemoglobin of 11.3 (9.4 – 12.8) g/dL and remain
transfusion free
In long-term follow-up, 53% (9/17) of patients
who achieved transfusion independence and restarted iron chelation
have since stopped; 30% (7/23) who achieved transfusion
independence now receive phlebotomy to reduce iron levels
bluebird bio, Inc. (Nasdaq: BLUE) today presented updated
long-term efficacy and safety results reflecting up to six years of
data for betibeglogene autotemcel gene therapy (beti-cel; formerly
LentiGlobin™ for β-thalassemia) in patients with
transfusion-dependent β-thalassemia (TDT). The company also
presented results for pediatric patients in the Phase 3 HGB-207
(Northstar-2) and HGB-212 (Northstar-3) studies. These data were
presented at the 62nd American Society of Hematology (ASH) Annual
Meeting and Exposition, taking place virtually from December 5-8,
2020.
“Our vision for beti-cel gene therapy is that a one-time
treatment would enable lifelong, stable production of functional
hemoglobin at sufficient levels to allow patients with
β-thalassemia to stop and remain free from blood transfusions,”
said David Davidson, M.D., chief medical officer, bluebird bio.
“All of the patients in our Phase 3 studies who achieved
transfusion independence have maintained it, with the durability of
the treatment effect underscored by patients from our earlier
studies reaching their five-year anniversaries of freedom from
transfusions. Moreover, transfusion independence has been observed
in pediatric, adolescent and adult patients, and across genotypes –
suggesting consistent outcomes with beti-cel regardless of age or
genotype.”
TDT is a severe genetic disease caused by mutations in the
β-globin gene that result in reduced or significantly reduced
hemoglobin (Hb). In order to survive, people with TDT require
chronic blood transfusions to maintain adequate Hb levels. These
transfusions carry the risk of progressive multi-organ damage due
to unavoidable iron overload.
Beti-cel is a one-time gene therapy that adds functional copies
of a modified form of the β-globin gene (βA-T87Q-globin gene) into
a patient’s own hematopoietic (blood) stem cells (HSCs). Once a
patient has the βA-T87Q-globin gene, they have the potential to
produce HbAT87Q, which is gene therapy-derived adult Hb, at levels
that may eliminate or significantly reduce the need for
transfusions. In studies of beti-cel, transfusion independence (TI)
is defined as no longer needing red blood cell transfusions for at
least 12 months while maintaining a weighted average Hb of at least
9 g/dL.
As of the data cut-off of March 3, 2020, a total of 60
pediatric, adolescent and adult patients, including 10 patients
with at least five years of follow-up and one with at least six
years, across genotypes of TDT have been treated with beti-cel in
the Phase 1/2 HGB-204 (Northstar) and HGB-205 studies, and the
Phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) studies.
Data from bluebird bio’s Phase 1/2 and Phase 3 clinical studies
represent more than 160 years of patient experience with
beti-cel.
Long-term follow-up study LTF-303: Efficacy
After participating in and completing the two years of follow-up
in either Phase 1/2 studies (HGB-204, HGB-205), or in one of the
Phase 3 studies (HGB-207, HGB-212), patients treated with beti-cel
were invited to enroll in the 13-year long-term follow-up study,
LTF-303. As of March 3, 2020, 32 patients were enrolled in LTF-303
(22 treated in Phase 1/2 studies, 10 treated in Phase 3 studies)
with a median post-infusion follow-up of 49.1 months (min-max: 23.3
– 71.8 months).
Of the 32 patients enrolled in LTF-303, TI was achieved in 14/22
(64%) patients treated in Phase 1/2 and in 9/10 (90%) patients
treated in Phase 3. All patients who achieved TI remained free from
transfusions [median duration of ongoing TI is 39.4 months
(min-max: 19.4 – 69.4 months)].
Weighted average Hb in patients who achieved TI in the Phase 1/2
was 10.4 (min-max: 9.4 – 13.3) g/dL and 12.5 (min-max: 11.9 – 13.5)
g/dL in patients who achieved TI in the Phase 3 studies.
Median gene therapy-derived hemoglobin (HbAT87Q) in all patients
treated in the Phase 1/2 studies was stable over time: 6.4
(min-max: 0.5 – 10.1) g/dL at Month 24 (n=22), 6.7 (min-max: 0.4 –
10.1) g/dL at Month 36 (n=22), 6.6 (min-max: 0.5 – 10.7) g/dL at
Month 48 (n=22), and 7.1 (min-max: 2.8 – 11.2) g/dL at Month 60
(n=10). Median HbAT87Q at Month 24 in all patients treated in the
Phase 3 studies was 9.5 (min-max: 0.9 – 12.4) g/dL (n=10).
Following an initial increase in liver iron concentration (LIC)
after infusion, LIC in patients who achieved TI decreased,
particularly in patients with a high iron burden at baseline.
Patients with severe (LIC >15 mg/g, n=2) and significant (LIC ≥7
– 15 mg/g, n=5) iron burden at baseline had a median reduction of
59% and 38%, respectively, from baseline to Month 48.
Prior to beti-cel infusion, all patients were on iron chelation,
which is needed to reduce excess iron caused by chronic blood
transfusions. Of the 23 patients who achieved TI following
treatment with beti-cel, the majority (65%, n=15) discontinued iron
chelation and 30% (7/23) were able to receive phlebotomy (blood
removal), which is a preferred method for iron reduction.
Long-term follow-up study LTF-303: Safety
In LTF-303, there were no deaths, no graft-versus-host disease
(GVHD), and no cases of replication-competent lentivirus,
insertional oncogenesis or clonal dominance were observed. No
drug-related adverse events (AEs) were reported >2 years
post-infusion. Serious AEs during LTF-303 unrelated to beti-cel
included gonadotropic insufficiency, ectopic pregnancy, gall
bladder wall thickening/polyp, bacteremia, neutropenia and major
depression (n=1 for each).
Phase 3 Pediatric Patients: Efficacy
As of March 3, 2020, 24 pediatric patients (<12 years: n=13;
≥12 to <18 years: n=11) were treated and had a median follow-up
of 15.5 months (min-max: 1.1 – 29.5 months) in Phase 3 HGB-207
(Northstar-2) and HGB-212 (Northstar-3) studies.
In these Phase 3 studies, the median age at which the children
under 12 received their first transfusion was 11 months of age; for
the adolescents between the ages of 12 and 18, the median was eight
months of age.
Following treatment with beti-cel, 87% (13/15) of evaluable
patients under the age of 18 years, including four patients under
age 12, achieved TI. As of March 3, 2020, these patients continue
to be free of transfusions for a median duration of 14.9 months
(min-max: 12.2 – 21.6 months), with median weighted average total
Hb levels of 11.3 g/dL (min-max: 9.4 – 12.8 g/dL).
Phase 3 Pediatric Patients: Safety
Drug-related AEs in pediatric patients during the HGB-207 and
HGB-212 trials were non-serious and included tachycardia (Grade 1,
n=1) and abdominal pain (Grade 1, n=2) on the day of infusion, and
Grade 3 thrombocytopenia in one patient post-infusion. There were
no deaths, no GVHD, no graft failures, and no cases of
replication-competent lentivirus, insertional oncogenesis or clonal
dominance were observed.
Post-infusion non-hematologic Grade ≥3 AEs in ≥3 patients <
18 years of age (N=24) included stomatitis (n=14), febrile
neutropenia (n=12), decreased appetite (n=5), epistaxis (n=4),
alanine aminotransferase increase (n=3), hypoxia (n=3) and pyrexia
(n=3).
The presentations are now available on demand on the ASH
conference website:
- Oral #153: Long-Term Efficacy and Safety of
Betibeglogene Autotemcel Gene Therapy for the Treatment of
Transfusion-Dependent β-Thalassemia: Results in Patients with up to
6 Years of Follow-up
- Oral #154: Favorable Outcomes in Pediatric Patients in
the Phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) Studies
of betibeglogene autotemcel Gene Therapy for the Treatment of
Transfusion-dependent β-thalassemia
- Poster #776: Improvement in Erythropoiesis Following
Treatment with Betibeglogene Autotemcel Gene Therapy in Patients
with Transfusion-Dependent β-Thalassemia in the Phase 3 HGB-207
Study
- Poster #1699: Response of Patients with
Transfusion-dependent β-thalassemia (TDT) to betibeglogene
autotemcel (beti-cel; LentiGlobin for β-thalassemia) Gene Therapy
Based on HBB Genotype and Disease Genetic Modifiers
About betibeglogene
autotemcel
The European Commission granted conditional marketing
authorization (CMA) for beti-cel, marketed as ZYNTEGLO™ 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.
Non-serious adverse events (AEs) observed during clinical
studies that were attributed to beti-cel included abdominal pain,
thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain
in extremity, tachycardia and non-cardiac chest pain. One serious
adverse event (SAE) of thrombocytopenia was considered possibly
related to beti-cel.
Additional AEs observed in clinical studies were consistent with
the known side effects of HSC collection and bone marrow ablation
with busulfan, including SAEs of veno-occlusive disease.
For details, please see the Summary of Product Characteristics
(SmPC).
On April 28, 2020, the European Medicines Agency (EMA) renewed
the CMA for beti-cel. The CMA for beti-cel is valid in the 27
member states of the EU as well as the UK, Iceland, Liechtenstein
and Norway.
The U.S. Food and Drug Administration granted beti-cel Orphan
Drug status and Breakthrough Therapy designation for the treatment
of TDT. Beti-cel is not approved in the U.S. Beti-cel continues to
be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and
Northstar-3 (HGB-212) studies.
bluebird bio is conducting a long-term safety and efficacy
follow-up study (LTF-303) for people who have participated in
bluebird bio-sponsored clinical studies of beti-cel.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our
Cambridge, Mass., headquarters, we’re developing gene and cell
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: cerebral adrenoleukodystrophy, sickle cell disease,
β-thalassemia and multiple myeloma, using gene and cell therapy
technologies including gene addition, 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, LentiGlobin and bluebird bio are trademarks of
bluebird bio, Inc.
Forward-Looking Statements
This release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995.
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: regarding the potential for betibeglogene
autotemcel to treat transfusion-dependent β-thalassemia and the
risk that the efficacy and safety results from our prior and
ongoing clinical trials will not continue or be repeated in our
ongoing or planned clinical trials; the risk that the current or
planned clinical trials of our product candidates will be
insufficient to support regulatory submissions or marketing
approval in the United States, or for a broader indication in the
European Union; the risk that regulatory authorities will require
additional information regarding our product candidates, resulting
in delay to our anticipated timelines for regulatory submissions,
including our applications for marketing approval; and the risk
that any one or more of our product candidates, will not be
successfully developed, approved or commercialized. 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-Q, 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20201205005037/en/
Media: Catherine Falcetti, 339-499-9436
cfalcetti@bluebirdbio.com
Investors: Ingrid Goldberg, 857-217-0490
Igoldberg@bluebirdbio.com
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