Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT) today
announced that the Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) adopted a
positive opinion recommending marketing authorization for Oxbryta®
(voxelotor) tablets for the treatment of hemolytic
anemia due to sickle cell disease (SCD) in adults and pediatric
patients 12 years of age and older as monotherapy or in combination
with hydroxycarbamide (hydroxyurea). Oxbryta, an oral treatment
taken once daily, would be the first medicine available in Europe
that directly inhibits sickle hemoglobin (HbS) polymerization, the
molecular cause of sickling and destruction of red blood cells in
SCD.
Based on this CHMP opinion, a decision by the European
Commission (EC), which authorizes marketing approval in the
European Union, is expected in the first quarter of 2022. If
approved by the EC, Oxbryta will receive marketing authorization in
all EU member states and Iceland, Liechtenstein and Norway.
“For far too long, people battling the devastating effects of
sickle cell disease have had few therapeutic options. This positive
CHMP opinion marks an important step forward to a new medicine for
tens of thousands of people in Europe living with the disease,”
said Ted W. Love, M.D., president and chief executive
officer of GBT. “By targeting the underlying cause, we believe
Oxbryta has the potential to address severe complications
experienced by patients throughout their life that ultimately lead
to shortened life expectancy.”
People living with SCD and those closest to them experience a
lifelong journey with the disease that touches every aspect of
their lives. Patients experience progressive, serious complications
and morbidities, including end-organ damage, which lead to
decreased quality of life and early mortality.1 Furthermore,
economic disadvantages and health inequalities experienced by many
patients with SCD can have negative societal impacts in areas such
as access to healthcare, education and employment.2-8
“The positive CHMP decision is of huge significance for the SCD
community, and as a clinician I would welcome the availability of
this new therapeutic approach for my patients,” said Professor
Mariane de Montalembert, co-head of the Necker Site for major
sickle cell syndromes and other rare pathologies of red blood cells
and erythropoiesis, Necker-Enfants Malades Hospital, Sickle Cell
Center in Paris. “In clinical studies, voxelotor has demonstrated
significant increases in hemoglobin levels and reductions in
markers of hemolysis, which is expected to improve quality of life
and, we hope, to reduce chronic organ damage associated with the
disease.”
The CHMP opinion is based on data demonstrating clinically
meaningful and statistically significant improvements in hemoglobin
(Hb) levels, accompanied by reductions in red blood cell
destruction (hemolysis), for patients treated with Oxbryta. Data
from the Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to
Inhibit HbS PolymErization) Study of 274 patients 12 years of age
and older with SCD showed that, after 24 weeks of treatment, 51.1%
of patients receiving Oxbryta achieved a greater than 1 g/dL
increase in Hb compared with 6.5% receiving placebo (p<0.001),
with significant improvements in markers of hemolysis in indirect
bilirubin and reticulocyte percentage.9 Results from the HOPE Study
were published in June 2019 in The New England Journal of Medicine.
Oxbryta showed a favorable safety profile with limited and
transitory adverse reactions. The most common adverse reactions
occurring in ≥10% of patients treated with Oxbryta with a
difference of >3% compared to placebo were headache (26% vs.
22%), diarrhea (20% vs. 10%), abdominal pain (19% vs. 13%), nausea
(17% vs. 10%), fatigue (14% vs. 10%), rash (14% vs. 10%) and
pyrexia (12% vs. 7%).9
The analysis of the complete data from the HOPE Study, published
in The Lancet Haematology in April 2021, further demonstrated that
Oxbryta, at a daily dose of 1,500 mg, resulted in rapid and durable
improvements in Hb levels and markers of hemolysis over 72 weeks of
treatment in SCD patients 12 years of age and older. At 72 weeks,
88.9% of patients receiving Oxbryta achieved a greater than 1 g/dL
increase in Hb compared with 25% receiving placebo. In addition, at
72 weeks, 58.9% of patients receiving Oxbryta achieved a greater
than 2 g/dL increase in Hb compared with 3.3% receiving placebo and
20.0% of patients receiving Oxbryta achieved a greater than 3 g/dL
increase in Hb compared to 0% receiving placebo. The analysis also
showed that study participants treated with Oxbryta had numerically
fewer vaso-occlusive crises (VOCs), consistent with the trends at
24 weeks, and were three times less likely to experience an acute
episode (decrease in Hb >2 g/dL from baseline). Treatment with
Oxbryta was well tolerated, with no new safety or tolerability
findings identified.10
Findings from a post-hoc analysis of the HOPE Study published in
the American Journal of Hematology in January 2021 evaluated the
incidence and outcomes of leg ulcers in SCD patients and further
support the foundational role of HbS polymerization inhibition in
SCD treatment. Results of the analysis showed leg ulcers improved
or resolved by week 72 in all patients (5 of 5) receiving Oxbryta
1,500 mg, compared with 63% of patients (5 of 8) in the placebo
group.11
Oxbryta is currently approved in the United States for the
treatment of SCD in adults and children 12 years of age and
older.12 GBT is 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 of age. 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.
About Sickle Cell Disease Sickle cell
disease (SCD) affects more than 100,000 people in the United
States,13 an estimated 52,000 people in Europe,14 and millions of
people throughout the world, particularly among those whose
ancestors are from sub-Saharan Africa.13 It also affects people of
Hispanic, South Asian, Southern European and Middle Eastern
ancestry.13 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.15 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, crescent-shaped and
rigid.1, 15-16 The recurrent sickling process causes destruction of
the red blood cells and 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 delivery
throughout the body. The diminished oxygen delivery to tissues and
organs can lead to life-threatening complications, including stroke
and irreversible organ damage.1, 16-18 Complications of SCD begin
in early childhood and can include neurocognitive impairment, acute
chest syndrome, and overt stroke, among other serious issues.19
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 leading to hemolysis and hemolytic
anemia, 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 in the United States, 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).
FDA-Approved IndicationOxbryta is a hemoglobin
S polymerization inhibitor indicated for the treatment of sickle
cell disease in adults and pediatric patients 12 years of age and
older.
This indication is approved under accelerated approval based on
increase in hemoglobin (Hb). Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in confirmatory trial(s).12
FDA-Approved 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 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 Global Blood Therapeutics Global
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 (HbS) 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
development to address pain crises associated with the disease, and
GBT021601 (GBT601), the company’s next generation HbS
polymerization inhibitor. In addition, GBT’s drug discovery teams
are working on new targets to develop the next generation of
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 the CHMP opinion for Oxbryta and potential and timing of a
decision of the European Commission; ongoing and planned studies,
clinical trials and registries and related protocols, activities,
timing and other 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; 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
- Kato GJ, et al. Sickle cell disease. Nat Rev Dis Primers.
2018;4:18010
- McClish DK, et al. Health related quality of life in sickle
cell patients: the PiSCES project. Health Qual Life Outcomes.
2005;3:50.
- Daniel LC, et al. Lessons Learned From a Randomized Controlled
Trial of a Family-Based Intervention to Promote School Functioning
for School-Age Children With Sickle Cell Disease. J Pediatr
Psychol. 2015;40:1085-1094.
- Dampier C, et al. Health-related quality of life in adults with
sickle cell disease (SCD): a report from the comprehensive sickle
cell centers clinical trial consortium. Am J Hematol.
2011;86:203-205.
- Dampier C, et al. Health-related quality of life in children
with sickle cell disease: a report from the Comprehensive Sickle
Cell Centers Clinical Trial Consortium. Pediatr Blood Cancer.
2010;55:485-494.
- Anie KA, et al. Sickle cell disease: Pain, coping and quality
of life in a study of adults in the UK. Br J Health Psychol.
2002;7:331-344.
- Kambasu DM, et al. Health-related quality of life of
adolescents with sickle cell disease in sub-Saharan Africa: a
cross-sectional study. BMC Hematol. 2019;19:9.
- Lubeck D, et al. Estimated Life Expectancy and Income of
Patients With Sickle Cell Disease Compared With Those Without
Sickle Cell Disease. JAMA Netw Open. 2019;2:e1915374.
- Vichinsky E, et al. A Phase 3 Randomized Trial of Voxelotor in
Sickle Cell Disease. N Engl J Med.
2019;381:509-519.
- Howard, J., et al., Voxelotor in adolescents and adults with
sickle cell disease (HOPE): long-term follow-up results of an
international, randomised, double-blind, placebo-controlled, phase
3 trial. Lancet Haematol, 2021. 8(5): p. e323-e333.
- Minniti CP, et al. The impact of voxelotor treatment on leg
ulcers in patients with sickle cell disease. Am J Hematol.
2021.
- Oxbryta (voxelotor) tablets prescribing information. South San
Francisco, Calif. Global Blood Therapeutics, Inc.; November
2019.
- Centers for Disease Control and Prevention website. Sickle Cell
Disease (SCD). https://www.cdc.gov/ncbddd/sicklecell/data.html.
Accessed December, 2021.
- European Medicines Agency.
https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182125.
Accessed December, 2021.
- National Heart, Lung, and Blood Institute website. Sickle Cell
Disease.
https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease.
Accessed December, 2021.
- Rees DC, et al. Sickle cell disease. Lancet.
2010;376(9757):2018-2031.
- Kato GJ et al. Intravascular hemolysis and the pathophysiology
of sickle cell disease. J Clin Invest. 2017;127:750-760.
- Caboot JB, et al. Hypoxemia in sickle cell disease:
significance and management Paediatr Respir Rev.
2014;15(1):17-23.
- Cooper TE et al. Pharmacological interventions for painful
sickle cell vaso-occlusive crises in adults. Cochrane Database of
Systematic Reviews. 2019.
Contact:
Steven Immergut (media) +1 650 410
3258 simmergut@gbt.com |
Claudia Nabaie (media Europe) +41 79 906 5814
cnabaie@gbt.com |
Courtney Roberts (investors) +1 650 351
7881 croberts@gbt.com |
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