Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT) today announced
updates across several of its development programs in sickle cell
disease (SCD). The company has submitted a supplemental New Drug
Application (sNDA) to the U.S. Food and Drug Administration (FDA)
seeking accelerated approval for Oxbryta® (voxelotor) for the
treatment of SCD in children ages 4 to 11 years, together with a
related separate New Drug Application (NDA) required to seek
approval for a pediatric weight-based formulation of Oxbryta.
Additionally, GBT initiated two global, randomized,
placebo-controlled, pivotal Phase 3 clinical trials of inclacumab,
a novel P-selectin inhibitor. The company also enrolled the first
SCD patient in a Phase 1 study evaluating GBT021601 (GBT601), a
next-generation hemoglobin S (HbS) polymerization inhibitor, in
people with SCD.
“Starting at a very early age, sickle cell
disease has a serious and life-altering impact on children, and
current therapeutic options for children under 12 years of age are
limited. We believe there is significant potential to impact the
longer-term outcomes by addressing the root cause of red blood cell
sickling at a young age,” said Ted W. Love, M.D., president and CEO
of GBT. “Our team is committed to working closely with the FDA to
potentially expand access to Oxbryta, thereby providing hope to
families.”The Oxbryta pediatric sNDA and NDA include data from the
open-label Phase 2a HOPE-KIDS 1 Study (GBT440-007). An analysis of
data presented at the European Hematology Association (EHA) 2021
Virtual Congress in 45 children with SCD ages 4 to 11 years
enrolled in the study showed that weight-based treatment with
Oxbryta resulted in rapid and sustained improvements in hemoglobin.
Concurrent improvements in markers of hemolysis also were observed.
GBT requested priority review for the sNDA and NDA, which, if
granted, could result in a six-month review process. The FDA has a
60-day filing review period to determine whether the sNDA and the
NDA are complete and acceptable for filing.
Design and Initiation of Pivotal Phase 3
Clinical Trials of Inclacumab The two randomized,
double-blind, placebo-controlled Phase 3 clinical trials are
evaluating the safety and efficacy of inclacumab for the treatment
of vaso-occlusive crises (VOCs) associated with SCD. Both studies
are enrolling individuals with SCD age 12 years and older who have
experienced between two and 10 VOCs in the previous year.
Inclacumab selectively targets P-selectin, a protein that mediates
cell adhesion and is clinically validated to reduce pain
crises.
GBT2104-131 (NCT04935879) is evaluating the
effect of inclacumab on the frequency of VOCs. Approximately 240
patients will be randomized to an IV infusion of 30 mg/kg
inclacumab or placebo every 12 weeks. The primary outcome of this
Phase 3 trial is the rate of VOCs during the 48-week study period.
Secondary outcomes include time to first and second VOCs,
proportion of participants with no VOCs, rate of VOCs that required
admission to a healthcare facility and duration of inpatient
hospitalization for VOCs.
The second trial, GBT2104-132 (NCT04927247), is
evaluating the effect of a single dose of inclacumab on hospital
readmission rates. VOCs in SCD are a leading cause of hospital
readmissions1 and a significant burden on patients and healthcare
resources. In this Phase 3 trial, approximately 280 participants
who have been admitted to a healthcare facility due to a VOC will
be randomized to receive a one-time IV infusion of 30 mg/kg of
inclacumab or placebo in the peri-discharge window (just prior to,
during or around discharge). The primary outcome is the rate of
hospital readmissions for a VOC within 90 days following an initial
hospitalization for a VOC. Secondary outcomes include readmission
within 30 days, time to first hospital readmission for VOC and rate
of VOCs leading to healthcare provider visits.
“Our goal is to transform sickle cell disease
into a well-managed condition, and we are committed to advancing
our pipeline of innovative therapies that address the multiple
pathologies of this inherited disease in parallel with working to
expand access to Oxbryta. Vaso-occlusive crises take a significant
toll on patients and are a leading cause of hospital readmissions.
We believe inclacumab could be a best-in-class therapeutic option,
with the potential for less frequent dosing than existing
treatments,” said Kim Smith-Whitley, M.D., executive vice president
and head of research and development at GBT. “Our pipeline is the
engine of our commitment to improving the lives of people living
with this terrible disease. We are excited to initiate enrollment
in our two pivotal studies for inclacumab, in parallel with our
Phase 1 study of GBT601 in people with sickle cell disease.”
Design of Phase 1 Clinical Trial of
GBT601
GBT is currently enrolling patients in
GBT021601-012. This single and multiple ascending dose Phase 1
study is assessing the safety, tolerability, pharmacokinetics and
pharmacodynamics of GBT601 in up to six people with SCD ages 18 to
60 years. Patients with hemoglobin levels between 5.5 g/dL and 10.5
g/dL are eligible for enrollment. The primary outcome is the safety
and tolerability of GBT601 as assessed at 14 weeks. Secondary
outcomes include measures of pharmacokinetics and pharmacodynamics,
as well as an assessment of the relationship between GBT601 and
measures of anemia and hemolysis. GBT plans to submit preliminary
proof-of-concept data for GBT601 for presentation at a medical
meeting this year.
Discovered and designed by GBT’s research and
development team, GBT601 has the same mechanism of action as
Oxbryta, with the potential for greater efficacy by achieving
higher hemoglobin levels and occupancy at lower doses, as
demonstrated in preclinical studies. This study follows an ongoing
first-in-human trial to determine safe and tolerable dosing.
About Sickle Cell DiseaseSickle
cell disease (SCD) affects an estimated 100,000 people
in the United States,2 an estimated 52,000 people
in Europe,3 and millions of people throughout the world,
particularly among those whose ancestors are from sub-Saharan
Africa.2 It also affects people of Hispanic, South Asian,
Southern European and Middle Eastern ancestry.2 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.4 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.4-6 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.5-8
About
Oxbryta® (voxelotor)
tabletsOxbryta (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. On November 25, 2019, Oxbryta received U.S. Food and
Drug Administration (FDA) accelerated approval for the
treatment of SCD in adults and children 12 years of age and
older.9
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 15 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 has been
granted Priority Medicines (PRIME) designation from the European
Medicines Agency (EMA), and the European Commission (EC) has
designated Oxbryta as an orphan medicinal product for the treatment
of patients with SCD. Also, in May 2021, 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.
Important Safety
InformationOxbryta 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 2 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
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 Inclacumab Inclacumab is
a novel, fully human monoclonal antibody that selectively targets
P-selectin, a protein that mediates cell adhesion and is clinically
validated to reduce pain crises,10 known as vaso-occlusive crises
or VOCs, in people with sickle cell disease (SCD). Preclinical
results suggest that inclacumab has the potential to be a
best-in-class option for reducing VOCs in people with SCD, with the
potential for quarterly, rather than monthly dosing. GBT has
exclusive worldwide rights to inclacumab as part of the company’s
licensing agreement with F. Hoffmann-La Roche Ltd. The safety,
tolerability and pharmacokinetics of inclacumab have been evaluated
by Roche in more than 700 non-SCD patients.
About Global Blood
TherapeuticsGlobal Blood Therapeutics (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 treatment 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
Statements Certain 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 data presented at the EHA Congress,
including support for the use of Oxbryta in children; ongoing and
planned studies and clinical trials and related protocols,
activities and expectations; expanding access to Oxbryta, including
related activities and 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
review, timing and approval; altering the treatment, course and
care of SCD and mitigating related complications; potential impact
of addressing the root cause of red blood cell sickling at a young
age; 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
- Elixhauser A and Steiner C, HCUP Statistical Brief #153, April
2013
- Centers for Disease Control and Prevention website. Sickle
Cell Disease
(SCD). https://www.cdc.gov/ncbddd/sicklecell/data.html.
Accessed June 3, 2019.
- European Medicines Agency.
https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182125.
Accessed June 12, 2020.
- 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.
- Ataga K. et al. N Engl J Med. 2017;376(5):429-439.
Contact:Steven
Immergut (media)650.410.3258simmergut@gbt.com
Courtney
Roberts (investors)650.351.7881croberts@gbt.com
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