99.5% reduction in annualized rate of
vaso-occlusive crises (VOC) and acute chest syndrome (ACS) in Group
C patients with a history of VOCs and ACS (n=14) who had at least
six months follow-up
At up to 24 months, no reports of serious VOC
or ACS in Group C patients (n=18) with at least six months
follow-up
Group C patients with at least six months
follow-up continue to produce consistent levels of gene
therapy-derived anti-sickling hemoglobin (HbAT87Q) at up to 24
months, reducing levels of abnormal sickle hemoglobin (HbS)
Key markers of hemolysis approach near-normal
levels in Group C patients, supporting the potential of LentiGlobin
for SCD to modify the underlying pathophysiology of the disease
bluebird bio, Inc. (Nasdaq: BLUE) announced that new data
from its ongoing Phase 1/2 HGB-206 study of investigational
LentiGlobin™ gene therapy for adult and adolescent patients with
sickle cell disease (SCD) show a near-complete reduction of serious
vaso-occlusive crises (VOCs) and acute chest syndrome (ACS). These
data are being presented at the Virtual Edition of the 25th
European Hematology Association (EHA25) Annual Congress.
“Vaso-occlusive crises (VOCs) are the painful, life-threatening
episodes that are the primary clinical manifestation of sickle cell
disease. The nearly complete elimination of VOCs that we saw in
this study is impressive and demonstrates the potential of
LentiGlobin for SCD as a treatment for this serious disease,” said
David Davidson, M.D., chief medical officer, bluebird bio. “These
results illustrate the type of outcomes we believe are needed to
provide truly meaningful improvements for people living with sickle
cell disease. In addition, the improvement of laboratory measures
of hemolysis and red cell physiology, with nearly pan-cellular
distribution of the anti-sickling HbAT87Q, suggest LentiGlobin for
SCD may substantially modify the causative pathophysiology of SCD.
We are pleased to have reached a general agreement with the FDA on
the clinical data required to support a submission for LentiGlobin
for SCD and we plan to seek an accelerated approval. We look
forward to working with the entire SCD community to bring forward a
disease modifying option for patients.”
SCD is a serious, progressive and debilitating genetic disease
caused by a mutation in the β-globin gene that leads to the
production of abnormal sickle hemoglobin (HbS). HbS causes red
blood cells to become sickled and fragile, resulting in chronic
hemolytic anemia, vasculopathy and unpredictable, painful VOCs. For
adults and children living with SCD, this means painful crises and
other life altering or life-threatening acute complications—such as
ACS, stroke and infections. If patients survive the acute
complications, vasculopathy and end-organ damage, resulting
complications can lead to pulmonary hypertension, renal failure and
early death; in the U.S. the median age of death for someone with
sickle cell disease is 43 - 46 years.
“As a physician treating sickle cell for over 10 years, the
excruciating pain crises that my patients suffer from is one of the
most challenging and frustrating aspects of this disease,” said
presenting study author Julie Kanter, M.D., University of Alabama
at Birmingham. “The promising results of this study, which show
patients have an almost complete elimination of VOCs and ACS,
suggest LentiGlobin for SCD has real potential to provide a
significant impact for people living with sickle cell disease.”
LentiGlobin for SCD was designed to add 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
patients have the βA-T87Q-globin gene, their red blood cells can
produce anti-sickling hemoglobin, HbAT87Q, that decreases the
proportion of HbS, with the goal of reducing sickled red blood
cells, hemolysis and other complications.
As of March 3, 2020, a total of 37 patients have been treated
with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206
(n=34) clinical studies. The HGB-206 total includes: Group A (n=7),
B (n=2) and C (n=25).
HGB-206: Group C Updated Efficacy Results
In Group C of HGB-206, 25 patients were treated with LentiGlobin
for SCD and have up to 24.8 months of follow-up (median of 12.1;
min.-max.: 2.8—24.8 months). Results from Group C are as of March
3, 2020 and include efficacy data for 16 patients who had at least
a Month 6 visit, and safety data for 18 patients, which includes
two patients who were at least six months post-treatment but
results from a Month 6 visit are not available.
In 16 patients with six or more months of follow-up, median
levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q,
were maintained with HbAT87Q contributing at least 40% of total
hemoglobin. At last visit reported, total hemoglobin ranged from
9.6 – 16.2 g/dL and HbAT87Q levels ranged from 2.7 – 9.4 g/dL. At
Month 6 the production of HbAT87Q was associated with a reduction
in the proportion of HbS in total hemoglobin. Patients had a median
of ≤ 60% HbS. All patients in Group C were able to stop regular
blood transfusions and remain off transfusions at three months
post-treatment.
There was a 99.5% mean reduction in annualized rate of VOC and
ACS among the 14 patients who had at least six months of follow-up
and a history of VOCs or ACS, defined as four or more VOC or ACS
events in the two years prior to treatment. These 14 patients had a
median of eight events in the two years prior to treatment
(min.-max.: 4 – 28 events).
There were no reports of serious VOCs or ACS at up to 24 months
post-treatment in patients with at least six months of follow-up
(n=18). As previously reported, one non-serious Grade 2 VOC was
observed in a patient approximately 3.5 months post-treatment with
LentiGlobin for SCD.
In sickle cell disease, red blood cells become sickled and
fragile, rupturing more easily than healthy red blood cells. The
breakdown of red blood cells is hemolysis and this process occurs
normally in the body. However, in sickle cell disease hemolysis
happens too quickly due to the fragility of the red blood cells,
which results in hemolytic anemia.
Patients treated with LentiGlobin for SCD demonstrated
improvement in key markers of hemolysis, which are indicators of
the health of red blood cells. Lab results assessing these
indicators were available for the majority of the 18 patients with
6 months of follow-up. The medians for reticulocyte counts (n=15),
lactate dehydrogenase (LDH) levels (n=13) and total bilirubin
(n=16) improved compared to screening and stabilized by Month 6. In
patients with Month 24 data (n=5) these values approached the upper
limit of normal by Month 24. These results suggest treatment with
LentiGlobin for SCD is improving biological markers of sickle cell
disease.
Assays were developed by bluebird bio to enable the detection of
HbAT87Q and HbS protein in individual red blood cells as well as to
assess if HbAT87Q was pancellular, present throughout all of a
patient’s red blood cells. Samples from a subset of patients in
Group C were assessed. In nine patients who had at least six months
of follow-up, the average proportion of red blood cells positive
for HbAT87Q was greater than 70%, and on average more than 85% of
red blood cells contained HbAT87Q at 18 months post-treatment,
suggesting near-complete pancellularity of HbAT87Q
distribution.
HGB-206: Group C Safety Results
As of March 3, 2020, the safety data from all patients in
HGB-206 are generally reflective of underlying SCD and the known
side effects of hematopoietic stem cell collection and
myeloablative conditioning. There were no serious adverse events
related to LentiGlobin for SCD, and the non-serious, related
adverse events (AEs) were mild-to-moderate in intensity and
self-limited.
One patient with a history of frequent pre-treatment VOE,
pulmonary and systemic hypertension, venous thrombosis, obesity,
sleep apnea and asthma had complete resolution of VOEs following
treatment, but suffered sudden death 20 months after treatment with
LentiGlobin for SCD. The patient’s autopsy revealed cardiac
enlargement and fibrosis, and concluded the cause of death was
cardiovascular, with contributions from SCD and asthma. The
treating physician and an independent monitoring committee agreed
this death was unlikely related to LentiGlobin for SCD gene
therapy.
The presentation is now available on demand on the EHA25
website:
- Abstract #S282: “Outcomes in patients treated with
LentiGlobin for sickle cell disease (SCD) gene therapy: Updated
results from the Phase 1/2 HGB-206 group C study”
About HGB-206
HGB-206 is an ongoing, Phase 1/2 open-label study designed to
evaluate the efficacy and safety of LentiGlobin gene therapy for
SCD that includes three treatment cohorts: Groups A (n=7), B (n=2)
and C (n=25). A refined manufacturing process that was designed to
increase vector copy number (VCN) and improve engraftment potential
of gene-modified stem cells was used for Group C. Group C patients
also received LentiGlobin for SCD made from HSCs collected from
peripheral blood after mobilization with plerixafor, rather than
via bone marrow harvest, which was used in Groups A and B of
HGB-206.
LentiGlobin for Sickle Cell Disease Regulatory Status
bluebird bio reached general agreement with the U.S. Food and
Drug Administration (FDA) that the clinical data package required
to support a Biologics Licensing Application (BLA) submission for
LentiGlobin for SCD will be based on data from a portion of
patients in the HGB-206 study Group C that have already been
treated. The planned submission will be based on an analysis using
complete resolution of severe vaso-occlusive events (VOEs) as the
primary endpoint with at least 18 months of follow-up
post-treatment with LentiGlobin for SCD. Globin response will be
used as a key secondary endpoint.
bluebird bio anticipates additional guidance from the FDA
regarding the commercial manufacturing process, including
suspension lentiviral vector. bluebird bio announced in a May 11,
2020 press release it plans to seek an accelerated approval and
expects to submit the U.S. BLA for SCD in the second half of
2021.
About LentiGlobin for Sickle Cell Disease
LentiGlobin for sickle cell disease is an investigational gene
therapy being studied as a potential treatment for SCD. bluebird
bio’s clinical development program for LentiGlobin for SCD includes
the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210
study.
LentiGlobin for SCD received orphan medicinal product
designation from the European Commission for the treatment of
SCD.
The U.S. FDA granted orphan drug designation, regenerative
medicine advanced therapy (RMAT) designation and rare pediatric
disease designation for LentiGlobin for SCD.
LentiGlobin for SCD is investigational and has not been approved
in any geography.
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 betibeglogene autotemcel
for β-thalassemia or LentiGlobin for SCD. For more information
visit:
https://www.bluebirdbio.com/our-science/clinical-trials or
clinicaltrials.gov and use identifier NCT02633943 for 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, including cerebral adrenoleukodystrophy, sickle cell
disease, 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.
LentiGlobin and bluebird bio are trademarks of bluebird bio,
Inc.
bluebird bio 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 development and
regulatory plans for the LentiGlobin for SCD product candidate, and
the company’s intentions regarding the timing for providing further
updates on the development of the product candidate. 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 the COVID-19 pandemic and
resulting impact on our operations and healthcare systems will
affect the execution of our development plans or the conduct of our
clinical studies; the risk that even if LentiGlobin for SCD
addresses ACS and VOC events, that it may not address progressive
organ damage experienced by patients with SCD; the risk that the
efficacy and safety results observed in the patients treated in our
prior and ongoing clinical trials of LentiGlobin for SCD may not
persist or be durable; the risk that the efficacy and safety
results from our prior and ongoing clinical trials will not
continue or be repeated in when treating additional patients in our
ongoing or planned clinical trials; the risk that the HGB-206 and
HGB-210 clinical studies as currently contemplated may be
insufficient to support regulatory submissions or marketing
approval in the United States and European Union; the risk that
regulatory authorities will require additional information
regarding our product candidate, resulting in a delay to our
anticipated timelines for regulatory submissions, including our
application for marketing 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-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/20200612005082/en/
Media: Catherine Falcetti, 339-499-9436
cfalcetti@bluebirdbio.com
Investors: Ingrid Goldberg, 410-960-5022
igoldberg@bluebirdbio.com
Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com
bluebird bio (NASDAQ:BLUE)
Historical Stock Chart
From Mar 2024 to Apr 2024
bluebird bio (NASDAQ:BLUE)
Historical Stock Chart
From Apr 2023 to Apr 2024