Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT) today announced
new data from a Phase 1 study of GBT021601 (GBT601), the company’s
investigational next-generation sickle hemoglobin (HbS)
polymerization inhibitor, that demonstrated average hemoglobin (Hb)
occupancy greater than 30% and improvements in hematologic
parameters in a cohort of six patients with sickle cell disease
(SCD) receiving multiple ascending doses (MAD) of GBT601. The study
also showed that single ascending doses (SAD) and MAD of GBT601
were well tolerated in both healthy volunteers and SCD patients.
These data are being presented today (Poster #3099) during the 63rd
American Society of Hematology (ASH) Annual Meeting and Exposition
in Atlanta, Georgia and online.
“These Phase 1 data of GBT601 are very encouraging and
demonstrate that in sickle cell disease patients we can achieve a
high target hemoglobin occupancy at daily doses lower than 500 mg,
while maintaining a favorable safety and tolerability profile.
Therefore, GBT601 has the potential to improve clinical outcomes in
people living with SCD, while reducing pill burden,” said Clark
Brown, M.D., Ph.D., director of sickle cell clinical research at
the Aflac Cancer and Blood Disorders Center of Children’s
Healthcare of Atlanta and lead investigator of the study. “I’m very
excited to continue to study GBT601 in more patients and with
longer follow up to seek to confirm the potential for GBT601 as a
potent, well-tolerated disease-modifying therapy for sickle cell
patients in a once-daily pill.”
Discovered and designed by GBT’s research team, GBT601 has the
same mechanism of action as Oxbryta® (voxelotor) tablets, which is
the first FDA-approved medicine that directly targets HbS
polymerization, the root cause of the sickling and destruction of
red blood cells in SCD. GBT601 is a unique molecular entity with
its own intellectual property. With these Phase 1 data, GBT
believes GBT601 has shown the potential for greater response than
Oxbryta by achieving higher Hb levels and occupancy at lower doses.
In prior research in an in vivo SCD mouse model, GBT601 treatment
led to substantial improvements in hematological parameters.1
Single and Multiple Ascending Doses of GBT601 in Adult
SCD Patients Six adult patients with SCD (HbSS genotype)
were studied in a single-arm, intra-patient single-dose and MAD
trial to evaluate the safety and tolerability of GBT601. Patients
were given a single dose of 100 mg during the SAD portion of the
study and then, following a washout period of eight weeks, during
the MAD portion of the study patients received a loading dose of
300 mg on day one and a 200 mg loading dose on day two, followed by
a daily maintenance dose of 50 mg for five weeks (MAD-1). This was
immediately followed by the second MAD phase, with patients
receiving a loading dose of 500 mg on the first day and a 400 mg
loading dose the next day, followed by a daily maintenance dose of
100 mg for three weeks (MAD-2). The primary endpoint of the study
was safety and tolerability and key secondary endpoints included
pharmacokinetics (PK) and pharmacodynamic (PD) and hematological
parameters.
GBT601 demonstrated a favorable tolerability profile in both the
SAD and MAD phases. In the study overall, the majority of
treatment-emergent adverse events (TEAEs) were grade 1 or 2 and not
related to GBT601. There were three TEAEs reported that were
related to GBT601 – one case of grade 2 headache and two cases of
grade 1 diarrhea. In addition, in the MAD phases, a total of three
vaso-occlusive crises (VOCs) occurred in two patients, grades 2, 3
and 4 – all deemed unrelated to GBT601. No TEAEs led to study
discontinuation.
At study completion (16 weeks), Hb occupancy averaged 32.6%
(range 19.7% to 41.8%) and Hb levels increased by up to 3.1 g/dL
(mean increase of 2.3 g/dL). During study treatment, all patients
demonstrated improvements in hematologic parameters, including
reticulocytes and absolute reticulocytes, lactate dehydrogenase
(LDH) and indirect bilirubin. In addition, improvements in red
blood cell health were seen in all patients as assessed by
Oxygenscan testing.
GBT believes these Phase 1 study results provide proof of
concept that a low dose of GBT601 in a once-daily pill should
achieve high target Hb occupancies. Incorporation of these data
into GBT’s PK model predicts that even higher Hb occupancies can be
achieved at relatively low doses, thus enabling GBT’s further
clinical development of this next generation HbS polymerization
inhibitor.
“These are the first published results of GBT601 in people
living with sickle cell disease and represent an important
milestone to potentially establish this innovative investigational
therapy as a functional cure in a once-daily pill. As such, we
believe that treatment with GBT601 has the potential to be able to
improve key lab measures and make sickle cell disease look like
sickle cell trait. Most importantly, this is an important step on
our continuing journey to bring more transformative therapeutic
options to as many SCD patients as possible,” said Ted W. Love,
M.D., president and chief executive officer of GBT. “We very much
look forward to continuing the rapid advancement of our clinical
development of GBT601 as we advance our work to transform SCD into
a benign, well managed condition.”
Multiple Ascending Doses of GBT601 in Healthy
VolunteersTen adult healthy volunteers were randomized to
receive GBT601 (at a 300 mg loading dose for three days followed by
a 15 mg daily maintenance dose for 11 days) or placebo over a
14-day period. GBT601 was well tolerated in all subjects. Average
Hb occupancy at this 15 mg dose was 16.0% at day 14.
An Oxbryta dose greater than 300 mg was needed to achieve a
similar occupancy in the equivalent Oxbryta healthy volunteer
study.2 This GBT601 healthy volunteer study is enrolling additional
cohorts of 10 healthy volunteers with a higher daily maintenance
dose.
Single Ascending Doses of GBT601 in Healthy
VolunteersPreliminary single-dose data of GBT601 in
healthy volunteers showed a linear dose-dependent increase in
percent Hb occupancy up to the highest dose evaluated, 2,200 mg.
From single doses of 50 to 2,200 mg, the mean preliminary Hb
occupancy ranged from 0.88 to 43.9%, respectively, exceeding the Hb
occupancies reported for healthy volunteers receiving single doses
of Oxbryta over a similar range. GBT601 showed linear PK, high
partitioning into red blood cells, and a dose-dependent increase in
percent Hb occupancy in healthy volunteers, and single ascending
doses were well tolerated. Most adverse events were grade 1 or 2,
with none indicative of tissue hypoxia.
Conference Call and Webcast Today at 12:00 p.m.
ET GBT will host a conference call for the investment
community today, Monday, December 13, 2021 at 12:00 pm ET to
discuss new data on its sickle cell programs presented at the ASH
Annual Meeting. A live webcast including presentation slides can be
accessed on GBT’s website at www.gbt.com in the Investors section.
The archived webcast will be available for three months following
the event. To participate in the conference call, please dial (877)
407-3982 (domestic) or +1 (201) 493-6780 (international).
About Sickle Cell DiseaseSickle cell disease
(SCD) affects more than 100,000 people in the United
States,3 an estimated 52,000 people in Europe,4 and
millions of people throughout the world, particularly among those
whose ancestors are from sub-Saharan Africa.5 It also affects
people of Hispanic, South Asian, Southern European and Middle
Eastern ancestry.5 Complications of SCD begin in early childhood
and can include neurocognitive impairment, acute chest syndrome,
and silent and overt stroke, among other serious issues.6 SCD is a
lifelong inherited rare blood disorder that impacts hemoglobin, a
protein carried by red blood cells that delivers oxygen to tissues
and organs throughout the body.7 Due to a genetic mutation,
individuals with SCD form abnormal hemoglobin known as sickle
hemoglobin. Through a process called hemoglobin polymerization, red
blood cells become sickled – deoxygenated, crescent-shaped and
rigid.7-9 The sickling process causes hemolytic anemia (low
hemoglobin due to red blood cell destruction) and blockages in
capillaries and small blood vessels, which impede the flow of blood
and oxygen throughout the body. The diminished oxygen delivery to
tissues and organs can lead to life-threatening complications,
including stroke and irreversible organ damage.8-11
About
Oxbryta® (voxelotor)
Tablets Oxbryta (voxelotor) is an oral, once-daily therapy
for patients with sickle cell disease (SCD). Oxbryta works by
increasing hemoglobin’s affinity for oxygen. Since oxygenated
sickle hemoglobin does not polymerize, Oxbryta inhibits sickle
hemoglobin polymerization and the resultant sickling and
destruction of red blood cells, which are primary pathologies faced
by every single person living with SCD. Through addressing
hemolytic anemia and improving oxygen delivery throughout the body,
GBT believes that Oxbryta has the potential to modify the course of
SCD. In November 2019, the U.S. Food and Drug
Administration (FDA) granted accelerated approval for Oxbryta
tablets for the treatment of SCD in adults and children 12 years of
age and older.12
As a condition of accelerated approval, GBT will continue to
study Oxbryta in the HOPE-KIDS 2 Study, a post-approval
confirmatory study using transcranial Doppler (TCD) flow velocity
to assess the ability of the therapy to decrease stroke risk in
children 2 to 14 years of age.
In recognition of the critical need for new SCD treatments, the
FDA granted Oxbryta Breakthrough Therapy, Fast Track, Orphan Drug,
and Rare Pediatric Disease designations for the treatment of
patients with SCD. Additionally, Oxbryta was granted Priority
Medicines (PRIME) designation from the European Medicines Agency
(EMA), Oxbryta was designated by the European Commission (EC) as an
orphan medicinal product for the treatment of patients with SCD,
and Oxbryta was granted Promising Innovative Medicine (PIM)
designation in the United Kingdom from the Medicines and Healthcare
products Regulatory Agency (MHRA).
The EMA has accepted for review GBT’s Marketing Authorization
Application (MAA) seeking full marketing authorization of Oxbryta
in Europe to treat hemolytic anemia in SCD patients ages 12 years
and older. GBT is also seeking regulatory approval to expand the
potential use of Oxbryta in the United States for the treatment of
SCD in children as young as 4 years old. The Ministry of Health and
Prevention (MOHAP) in the United Arab Emirates (UAE) has granted
marketing authorization for Oxbryta for the treatment of SCD in
adults and children 12 years of age and older.
Important Safety Information Oxbryta should not
be taken if the patient has had an allergic reaction to voxelotor
or any of the ingredients in Oxbryta. See the end of the patient
leaflet for a list of the ingredients in Oxbryta.
Oxbryta can cause serious side effects, including serious
allergic reactions. Patients should tell their healthcare provider
or get emergency medical help right away if they get rash, hives,
shortness of breath, or swelling of the face.
Patients receiving exchange transfusions should talk to their
healthcare provider about possible difficulties with the
interpretation of certain blood tests when taking Oxbryta.
The most common side effects of Oxbryta include headache,
diarrhea, stomach (abdominal) pain, nausea, tiredness, rash and
fever. These are not all the possible side effects of Oxbryta.
Before taking Oxbryta, patients should tell their healthcare
provider about all medical conditions, including if they have liver
problems; if they are pregnant or plan to become pregnant as it is
not known if Oxbryta can harm an unborn baby; or if they are
breastfeeding or plan to breastfeed as it is not known if Oxbryta
can pass into breastmilk or if it can harm a baby. Patients should
not breastfeed during treatment with Oxbryta and for at least two
weeks after the last dose.
Patients should tell their healthcare provider about all the
medicines they take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements. Some medicines may
affect how Oxbryta works. Oxbryta may also affect how other
medicines work.
Patients are advised to call their doctor for medical advice
about side effects. Side effects can be reported to the FDA at
1-800-FDA-1088. Side effects can also be reported to Global
Blood Therapeutics at 1-833-428-4968 (1-833-GBT-4YOU).
Full Prescribing Information for Oxbryta is available
at Oxbryta.com.
About Global Blood TherapeuticsGlobal
Blood Therapeutics, Inc. (GBT) is a biopharmaceutical company
dedicated to the discovery, development and delivery of
life-changing treatments that provide hope to underserved patient
communities. Founded in 2011, GBT is delivering on its goal to
transform the treatment and care of sickle cell disease (SCD), a
lifelong, devastating inherited blood disorder. The company has
introduced Oxbryta® (voxelotor) tablets, the first
FDA-approved medicine that directly inhibits sickle hemoglobin
polymerization, the root cause of red blood cell sickling in SCD.
GBT is also advancing its pipeline program in SCD with inclacumab,
a P-selectin inhibitor in Phase 3 development to address pain
crises associated with the disease, and GBT021601 (GBT601), the
company’s next-generation hemoglobin S polymerization inhibitor. In
addition, GBT’s drug discovery teams are working on new targets to
develop the next wave of potential treatments for SCD. To learn
more, please visit www.gbt.com and follow the company on
Twitter @GBT_news.
Forward-Looking StatementsCertain statements in
this press release are forward-looking within the meaning of the
Private Securities Litigation Reform Act of 1995, including
statements containing the words “will,” “anticipates,” “plans,”
“believes,” “forecast,” “estimates,” “expects” and “intends,” or
similar expressions. These forward-looking statements are based on
GBT’s current expectations and actual results could differ
materially. Statements 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. GBT intends these forward-looking statements, including
statements regarding GBT’s priorities, dedication, commitment,
focus, goals, mission and vision; safety, efficacy and mechanism of
action of Oxbryta and other product characteristics; significance
of reducing sickling and hemolysis and raising hemoglobin;
commercialization, delivery, availability, use and commercial and
medical potential of Oxbryta; significance of GBT601 study results,
including providing proof of concept and demonstrating clinical and
therapeutic potential; the potential and continued development of
GBT601, including related expectations, activities and timing;
ongoing and planned studies, clinical trials and registries, and
related protocols, activities, timing and other expectations;
regulatory submissions to potentially expand the approved use of
Oxbryta for more patients and in a pediatric formulation in the
U.S. and to treat patients in Europe and other territories,
including potential regulatory review, timing and approval;
altering the treatment, course and care of SCD and mitigating
related complications; safety, efficacy, mechanism of action,
advancement and potential of GBT’s drug candidates and pipeline;
and working on new targets and discovering, developing and
delivering treatments, 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
GBT makes this statement for purposes of complying with those safe
harbor provisions. These forward-looking statements reflect GBT’s
current views about its plans, intentions, expectations, strategies
and prospects, which are based on the information currently
available to the company and on assumptions the company has made.
GBT 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 GBT’s control, including, without
limitation, risks and uncertainties relating to the COVID-19
pandemic, including the extent and duration of the impact on GBT’s
business, including commercialization activities, regulatory
efforts, research and development, corporate development activities
and operating results, which will depend on future developments
that are highly uncertain and cannot be accurately predicted, such
as the ultimate duration of the pandemic, travel restrictions,
quarantines, social distancing and business closure requirements in
the U.S. and in other countries, and the effectiveness of
actions taken globally to contain and treat the disease; the risks
that GBT is continuing to establish its commercialization
capabilities and may not be able to successfully commercialize
Oxbryta; risks associated with GBT’s dependence on third parties
for research, development, manufacture, distribution and
commercialization activities; government and third-party payer
actions, including those relating to reimbursement and pricing;
risks and uncertainties relating to competitive treatments and
other changes that may limit demand for Oxbryta; the risks
regulatory authorities may require additional studies or data to
support continued commercialization of Oxbryta; the risks that
drug-related adverse events may be observed during
commercialization or clinical development; data and results may not
meet regulatory requirements or otherwise be sufficient for further
development, regulatory review or approval; compliance with
obligations under the Pharmakon loan; and the timing and progress
of activities under GBT’s collaboration, license and distribution
agreements; along with those risks set forth in GBT’s Annual Report
on Form 10-K for the fiscal year ended December 31, 2020, and
in GBT’s most recent Quarterly Report on Form 10-Q filed with
the U.S. Securities and Exchange Commission, as well as
discussions of potential risks, uncertainties and other important
factors in GBT’s subsequent filings with the U.S. Securities
and Exchange Commission. Except as required by law, GBT assumes no
obligation to update publicly any forward-looking statements,
whether as a result of new information, future events or
otherwise.
References
- Dufu K, et al. GBT021601 Inhibits HbS Polymerization, Prevents
RBC Sickling and Improves the Pathophysiology of Sickle Cell
Disease in a Murine Model. American Society of Hematology
Conference 2020. December 2020.
https://www.gbt.com/wp-content/uploads/2020/12/201206-ASH-GBT20601-Poster.pdf
- Hutchaleelaha A, et al. Br J Clin Pharmacol. 2019
Jun;85(6):1290-1302.
- Centers for Disease Control and Prevention website. Sickle
Cell Disease
Research. https://www.cdc.gov/ncbddd/hemoglobinopathies/scdc-understanding-sickle-cell-disease.html.
Accessed December 1, 2021.
- European Medicines Agency.
https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182125.
Accessed June 12, 2020.
- Centers for Disease Control and Prevention website. Sickle
Cell Disease
(SCD). https://www.cdc.gov/ncbddd/sicklecell/data.html.
Accessed June 3, 2019.
- Kanter J, et al. Blood Rev. 2013 Nov;27(6):279-87.
- National Heart, Lung, and Blood Institute website.
Sickle Cell
Disease. https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease.
Accessed August 5, 2019.
- Rees DC, et al. Lancet. 2010;376(9757):2018-2031.
- Kato GJ, et al. Nat Rev Dis Primers. 2018;4:18010.
- Kato GJ, et al. J Clin Invest.
2017;127(3):750-760.
- Caboot JB, et al. Paediatr Respir Rev.
2014;15(1):17-23.
- Oxbryta (voxelotor) tablets prescribing information. South San
Francisco, Calif. Global Blood Therapeutics, Inc.; November
2019.
Contact:Steven Immergut (media)+1
650-410-3258simmergut@gbt.com
Courtney Roberts (investors)+1
650-351-7881croberts@gbt.com
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