Global Blood Therapeutics Presents GBT440 Data that Continue to Support Durability, Safety and Mechanism of Action in Sickle ...
October 07 2016 - 9:05AM
Global Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT), a
biopharmaceutical company developing novel therapeutics for the
treatment of grievous blood-based disorders with significant unmet
needs, today announced that an encore presentation of the
GBT440-001 study data supporting the durability, safety and
mechanism of action of GBT440 in sickle cell disease were presented
today in an oral session at the Academy for Sickle Cell and
Thalassemia (ASCAT) 10th Anniversary Conference in London.
“Hemoglobin oxygen affinity modulation is a very promising
approach for modifying disease in SCD because it intervenes on the
fundamental pathologic process- HbS polymerization. GBT440 is an
exciting hemoglobin modifier in development because of excellent
specificity and pharmaceutical properties resulting in both
increased potency and an improved safety profile. Over three months
of dosing, GBT440 has shown profound and durable reductions in
hemolysis and sickling, which provides further support that this
novel hemoglobin modifier has the potential to be a once-daily
treatment for patients with sickle cell disease,” said Dr. Jo
Howard, consultant hematologist and head of the red cell/sickle
cell service at Guy's and St Thomas' NHS Foundation Trust in
London. “Further, given that all 34 SCD patients dosed with GBT440
for 28 to 90 days have shown a positive hematologic response, I
believe that GBT440 could potentially transform the treatment of
this devastating disease.”
“The data showing a rapid and durable reduction in hemolytic
anemia and sickling over 90 days support both the mechanism of
action and the efficacy profile of GBT440 as a potentially
disease-modifying therapy for SCD,” said Ted W. Love, M.D.,
president and chief executive officer of GBT. “We are currently in
discussions with the FDA regarding details of our regulatory path
forward for GBT440 in SCD. Based on these promising results, we
believe that GBT440 has the potential to improve the clinical
course of sickle cell disease and look forward to exploring this
further in a pivotal trial that remains on track to initiate by
year-end. In addition, we look forward to presenting our full 90
day data for our 900 mg per day cohort at the upcoming American
Society of Hematology meeting.”
Design of Ongoing Phase 1/2 GBT440-001
TrialGBT440-001 is a randomized, placebo-controlled,
double-blind, single and multiple ascending dose study evaluating
the safety, tolerability, PK and PD of GBT440 in both healthy
subjects and patients with SCD. The study is being conducted in
three parts: Part A (single dose administration), Part B (multiple
dose administration, daily for 15 days in healthy subjects and 28
days in SCD patients) and Part C (multiple dose administration,
daily for 90 days in SCD patients).
Data Presentation HighlightsThe data presented
at ASCAT were previously presented at the European Hematology
Association's 21st Congress in June.
In the six patients treated with GBT440 700 mg/day for 90 days,
results showed:
- A durable reduction in hemolysis (red blood cell destruction)
from baseline to day 90, as evidenced by a rapid and sustained
reduction in bilirubin starting as early as day 4 and continuing
through day 90 (median decrease of greater than 35% compared with
an increase of approximately 20% with placebo).
- A median 1.1 g/dL increase in hemoglobin concentration with
GBT440 treatment compared with a 0.2 g/dL decrease with
placebo.
- A median decrease of approximately 20% in reticulocyte count
compared with an approximately 20% increase with placebo,
suggesting that the observed increase in hemoglobin is due to a
decrease in hemolysis.
- Steady improvement in hemoglobin and reticulocyte counts
through day 60 to 90 after initial variability of hemoglobin and
reticulocytes during the first 3-6 weeks (likely due to bone marrow
adjusting to dramatic reduction in hemolysis).
- A sustained reduction in irreversibly sickled cells, with a
median decrease of approximately 70% within 90 days compared to an
increase of approximately 15% with placebo.
- GBT440 was well tolerated over 90 days of dosing. The most
common adverse event was headache, seen in both the placebo and
GBT440 arms. There have been no drug-related serious adverse
events.
Complete 28-day results from three dosing cohorts of GBT440 (500
mg [n=10]), 700 mg [n=12] and 1,000 mg administered as 500 mg BID
[n=5]) showed:
- A consistent beneficial effect was seen in at least one key
parameter: hemolysis, reticulocytosis or sickle cell counts.
- The therapeutic target between 10-30% Hb modification was
achieved at GBT440 doses ≥500 mg.
GBT440-001 Overall Safety SummaryAcross the
GBT440 clinical development program, GBT440 has now been dosed in
252 adults, including 128 subjects in multiple dosing cohorts up to
90 days. It has been shown to be well tolerated with no
drug-related serious adverse events. There has been no evidence of
tissue hypoxia in healthy subjects up to approximately 40% Hb
modification or in SCD subjects up to approximately 30% Hb
modification.
About GBT440GBT is developing GBT440 as an
oral, once-daily therapy for patients with sickle cell disease.
GBT440, a hemoglobin modifier, works by increasing hemoglobin’s
affinity for oxygen. Since oxygenated sickle hemoglobin does not
polymerize, GBT believes GBT440 blocks polymerization and the
resultant sickling of red blood cells (RBCs). With the potential to
restore normal hemoglobin function and improve oxygen delivery,
GBT440 may be capable of modifying the progression of SCD. The U.S.
Food and Drug Administration (FDA) has granted GBT440 both Fast
Track and Orphan Drug designation for the treatment of patients
with SCD in recognition of the critical need for new
treatments.
About Global Blood Therapeutics Global
Blood Therapeutics, Inc. is a clinical-stage biopharmaceutical
company dedicated to discovering, developing and commercializing
novel therapeutics to treat grievous blood-based disorders with
significant unmet need. GBT is developing its lead product
candidate, GBT440, as an oral, once-daily therapy for sickle cell
disease (SCD) and is currently evaluating GBT440 in a Phase 1/2
study in both healthy subjects and adults with SCD and a Phase 2a
study in adolescents with SCD. GBT is also investigating GBT440 for
the treatment of hypoxemic pulmonary disorders in an ongoing Phase
2a study in patients with idiopathic pulmonary fibrosis.
Additionally, GBT is also engaged in research and development
activities with an oral kallikrein inhibitor for the prevention of
hereditary angioedema attacks. To learn more, please
visit: www.globalbloodtx.com.
Forward-Looking Statements Statements we
make in this press release may include statements that are not
historical facts and are considered forward-looking within the
meaning of Section 27A of the Securities Act of 1933, as amended
and Section 21E of the Securities Exchange Act of 1934, as amended.
We intend these forward-looking statements, including statements
regarding the therapeutic potential and safety profile of GBT440,
our ability to initiate a pivotal trial of GBT440 in SCD, our
ability to generate 90 day data from the 900 mg per day cohort in
our Phase 1/2 GBT440-001 trial, and the timing of these
events, to be covered by the safe harbor provisions for
forward-looking statements contained in Section 27A of the
Securities Act and Section 21E of the Securities Exchange Act and
are making this statement for purposes of complying with those safe
harbor provisions. These forward-looking statements reflect our
current views about our plans, intentions, expectations, strategies
and prospects, which are based on the information currently
available to us and on assumptions we have made. We can give no
assurance that the plans, intentions, expectations or strategies
will be attained or achieved, and furthermore, actual results may
differ materially from those described in the forward-looking
statements and will be affected by a variety of risks and factors
that are beyond our control including, without limitation, the
risks that our clinical and preclinical development activities may
be delayed or terminated for a variety of reasons, that regulatory
authorities may disagree with our clinical development plans or
require additional studies or data to support further clinical
investigation of our product candidate, and that GBT440 may not
provide the clinical benefits that we anticipate, along with those
set forth in our Annual Report on Form 10-K for the fiscal year
ended December 31, 2015, and in our Quarterly Report on
Form 10-Q for the quarter ended June 30, 2016, as well as
discussions of potential risks, uncertainties and other important
factors in our subsequent filings with the U.S. Securities and
Exchange Commission. Except as required by law, we assume no
obligation to update publicly any forward-looking statements,
whether as a result of new information, future events or
otherwise.
Contact Information:
Myesha Edwards (investors)
Global Blood Therapeutics
650-351-4730
investor@globalbloodtx.com
Julie Normart (media)
BrewLife
415-946-1087
media@globalbloodtx.com
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