--Results Showed GBT440 Treatment Led to Rapid,
Significant, Profound and Durable Reduction in Hemolysis and
Sickled Cells in All Patients Treated for Up to Six Months--
Global Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT) today announced
the presentation of results from its ongoing Phase 1/2 GBT440-001
study that further support the safety and efficacy profile of
GBT440 as a potentially disease-modifying therapy for sickle cell
disease (SCD). These data were presented at the 58th American
Society of Hematology (ASH) Annual Meeting & Exposition in San
Diego. Results showing how GBT440 is metabolized in healthy
subjects were also presented today.
“Sickle cell disease is one of the most common inherited
diseases worldwide and has a lifelong impact on those affected, who
experience severe daily symptoms of pain and fatigue, organ damage
and early mortality due to sickling and hemolytic anemia,” said Jo
Howard, MB BChir, MRCP, FRCPath, of Guy’s and St Thomas’ NHS
Foundation Trust. “The data we continue to gather, including
long-term dosing of up to six months, suggest that GBT440 has the
potential to improve outcomes in this serious disease. If so, that
would be a major breakthrough for the SCD community, which
currently has limited treatment options.”
“The six-month data show that GBT440 treatment leads to
clinically significant increases in hemoglobin and profound and
durable reductions in hemolysis and peripheral blood sickle cells.
These data, together with prior preclinical, clinical and safety
data, further support the excellent safety and tolerability for
GBT440 to date, and the design of the Phase 3 HOPE
(Hemoglobin Oxygen Affinity
Modulation to Inhibit HbS
PolymErization) Study,” said Ted
W. Love, M.D., president and chief executive officer of GBT. “We
have begun to initiate HOPE Study clinical trial sites and are
currently screening patients. The HOPE Study is designed to provide
a robust assessment of the ability of GBT440 to potentially
modify the course of SCD in a broad group of patients.”
Long-Term Dosing in Sickle Cell Disease Subjects with
GBT440, a Novel HbS Polymerization Inhibitor (abstract
#2488)GBT440-001 is a randomized, placebo-controlled,
double-blind, single and multiple ascending dose study. This
ongoing Phase 1/2 study is evaluating the safety, tolerability,
pharmacokinetics and pharmacodynamics of GBT440 in both healthy
subjects and adults 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). Some patients in Part C have taken
GBT440 for up to 6 months.
Results presented at ASH showed:
- All 41 SCD patients receiving GBT440 for up to six months have
shown a profound and durable reduction in hemolysis (red blood cell
destruction) as assessed by hemoglobin, reticulocytes and/or
bilirubin.
- All patients taking GBT440 showed profound and durable
reductions in irreversibly sickled cells compared with those taking
placebo.
- Results from Part C (dosing for at least 90 days) demonstrate
that among the 13 GBT440-treated patients:
- Patients treated with GBT440 for at least 90 days demonstrated
a clinically significant increase in hemoglobin (greater than 1
g/dL increase) compared with 14 placebo patients (46 percent vs. 0
percent; p=0.006).
- Patients treated with GBT440 had a sustained reduction in
irreversibly sickled cells compared with placebo treated patients
(-76.6 percent vs. +9.7 percent; p<0.001).
- GBT440 was well tolerated up to six months of dosing. The most
common treatment-related adverse events were Grade 1/2 headache and
gastrointestinal disorders, and occurred in similar rates in the
placebo and GBT440 arms. There were no drug-related serious or
severe adverse events. No sickle cell crises events occurred in
study participants while on GBT440. Exercise testing data showed
normal tissue oxygen delivery (no change in oxygen consumption
compared to placebo).
Absorption, Metabolism and Excretion of GBT440 a Novel
Hemoglobin S (HbS) Polymerization Inhibitor for the Treatment of
Sickle Cell Disease (SCD), in Healthy Male Subjects (abstract
#2487) Results of a study evaluating the pharmacokinetics,
metabolism and excretion of GBT440 given orally to healthy subjects
showed that the drug was completely excreted from the body, with a
half-life of approximately three days. This is much shorter than
the lifespan of a red blood cell (about 120 days) of a healthy
subject, suggesting that the binding of GBT440 to hemoglobin is a
reversible process. The data also suggest that the pharmacokinetics
of GBT440 are unlikely to be affected in patients with renal
disorders.
Investor Event Webcast DetailsTomorrow, Monday,
December 5, at 12:15 p.m. PT, members of GBT’s management team and
Drs. Jo Howard, Wally R. Smith of Virginia Commonwealth University,
and Jeremy Hobart of Peninsula Schools of Medicine and Dentistry
will review the ASH data presentations. The event will be
webcast live and will be available for replay from the Investors
section of GBT’s website at www.globalbloodtx.com for 30
days.
About GBT440 in Sickle Cell DiseaseGBT440 is
being developed as an oral, once-daily therapy for patients with
SCD. GBT440 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. With the potential to restore normal hemoglobin
function and improve oxygen delivery, GBT believes that GBT440 may
dramatically modify the course of SCD.
In recognition of the critical need for new SCD treatments, the
U.S. Food and Drug Administration (FDA) has granted GBT440 both
fast track and orphan drug designations and the European Commission
(EC) has designated GBT440 as an orphan medicinal product for the
treatment of patients with SCD. In addition to the ongoing Phase
1/2 GBT440-001 trial, GBT440 is being evaluated in an open-label,
single and multiple dose study in adolescents (age 12 to 17) with
SCD. This study is assessing the safety, tolerability,
pharmacokinetics and exploratory treatment effect of GBT440.
Additionally, GBT440 will be evaluated in the pivotal Phase 3
HOPE Study. This randomized, double-blind, placebo-controlled,
multi-national trial will enroll up to 400 patients age 12 and
older with SCD who have had at least one episode of vaso-occlusive
crisis (VOC) in the previous year. The study will be conducted in
two parts: Part A will compare GBT440 administered at doses of 900
or 1,500 mg per day vs. placebo in up to 150 patients treated for
at least 12 weeks, and Part B will include 250 patients randomized
to placebo or a dose of GBT440 based on Part A. The main objectives
of Part A are to select the optimal dose, define the final
secondary endpoints for Part B, and qualify the PRO instrument. The
primary efficacy endpoint of the HOPE Study is the proportion of
patients who achieve a greater than 1 g/dL increase in hemoglobin
at 24 weeks of treatment compared with baseline. Key secondary
efficacy endpoints include the effect of GBT440 on SCD symptom
exacerbation (as measured by the HOPE PRO instrument), overall SCD
symptoms, traditionally defined VOCs, hospitalizations and red
blood cell transfusions.
About Sickle Cell Disease (SCD)SCD is a
lifelong inherited blood disorder caused by a genetic mutation in
the beta-chain of hemoglobin, leading to formation of abnormal
hemoglobin known as sickle hemoglobin, or HbS. In its deoxygenated
state, HbS has a propensity to polymerize, or bind together forming
long, rigid rods within a red blood cell (RBC). The polymer rods
deform RBCs to assume a sickled shape and to become inflexible,
which can cause blockage in small blood vessels. Beginning in
childhood, SCD patients suffer unpredictable and recurrent episodes
or crises of severe pain due to blocked blood flow to organs, which
often lead to psychosocial and physical disabilities. This blocked
blood flow, combined with hemolytic anemia (the destruction of
RBCs), can eventually lead to multi-organ damage and early
death.
About Global Blood TherapeuticsGlobal 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 and will initiate its pivotal Phase 3 HOPE clinical trial
by the end of 2016. GBT is also investigating GBT440 for the
treatment of hypoxemic pulmonary disorders in two ongoing Phase 2a
studies in patients with idiopathic pulmonary fibrosis. 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 implement our clinical development plans for GBT440,
the timing of, and our ability to generate data from, our ongoing
Phase 1/2 clinical trial of GBT440 and our ability to enroll
patients in and begin screening in our HOPE Study, 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
candidates, and that drug-related adverse events may be observed in
later stages of clinical development, along with those risks set
forth in our Annual Report on Form 10-K for the fiscal year ended
December 31, 2015, and in our Quarterly Reports on Form 10-Q for
the quarters ended March 31, 2016, June 30, 2016 and September 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 Lacy (investors)
Global Blood Therapeutics
650-351-4730
investor@globalbloodtx.com
Julie Normart (media)
BrewLife
415-946-1087
media@globalbloodtx.com
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