GBT Presents Positive New Data on Oxbryta® (voxelotor) in Patients with Sickle Cell Disease at ASH Annual Meeting and Exposition

Real-world experience study of more than 3,100 patients demonstrates statistically significant reductions in transfusions, vaso-occlusive crises and hospitalizations in patients treated with Oxbryta

Phase 1 study of inclacumab also presented at ASH supports best-in-class potential as a quarterly-dosed P-selectin inhibitor

SOUTH SAN FRANCISCO, Calif., Dec. 12, 2021 (GLOBE NEWSWIRE) — Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT) today announced positive results from real-world and long-term studies with Oxbryta^® (voxelotor) tablets for the treatment of sickle cell disease (SCD). A first-in-class oral, once-daily therapy, Oxbryta directly inhibits sickle hemoglobin polymerization, the root cause of the sickling and destruction of red blood cells in SCD. Results from a large retrospective analysis of 3,128 SCD patients treated with Oxbryta showed a statistically significant improvement in hemoglobin (Hb) levels, and statistically significant reductions in transfusions, vaso-occlusive crises (VOCs) and hospitalizations. These data, as well as Phase 1 results for inclacumab, GBT’s investigational P-selectin inhibitor, were presented at the 63^rd American Society of Hematology (ASH) Annual Meeting & Exposition, taking place from December 11-14, 2021 in Atlanta, Georgia and online.

“We’re thrilled with the data presented at ASH, which demonstrate the clinically meaningful impact of Oxbryta for patients living with sickle cell disease. The benefits of Oxbryta were reinforced in this large retrospective study to evaluate the impact of an SCD medicine on clinical outcomes and healthcare resource utilization in a real-world setting,” said Kim Smith-Whitley, M.D., executive vice president and head of research and development of GBT. “We continue our commitment to the sickle cell disease community in our pursuit of developing innovative treatments that address the urgent needs of patients.”

Oxbryta Real-World Experience
A total of 3,128 SCD patients in the United States ages 12 and older were included in the retrospective analysis (Poster #2052) from the Symphony Health claims database. This study of medical and pharmacy claims for patients who initiated Oxbryta treatment between November 2019 and June 2021 compared annualized rates per patient-year (PPY) for transfusions, VOCs and VOC-related and all-cause hospitalizations for the three months before Oxbryta initiation versus the period after beginning the treatment. Among patients with at least one recent transfusion prior to initiating treatment, there was a 52% mean reduction in the number of transfusions after beginning Oxbryta. Patients with VOCs in the pre-study period experienced a mean reduction of 23% in the number of VOCs after initiating treatment. After starting Oxbryta, the mean number of VOC-related hospitalizations decreased by 34%, while the mean number of all-cause hospitalizations decreased by 37% among patients who were recently hospitalized. Approximately 61% of patients for whom Hb lab data were available showed increased Hb levels of greater than 1 g/dL during follow up – consistent with the results from the Phase 3 HOPE Study.

“These data presented at ASH contribute to the growing body of evidence on the real-world clinical benefit of Oxbryta, providing additional support for its use in the treatment of sickle cell disease and management of associated complications,” said Nirmish Shah, M.D., associate professor of medicine, pediatrics, Duke University School of Medicine. “It is encouraging that patients have an available innovative therapeutic option that has the potential to modify the course of this devastating disease.”

Additional Oxbryta Studies at ASH 2021
An analysis of an ongoing open-label extension (OLE) of the Phase 3 HOPE Study (Poster #3114; will be presented on December 13) confirmed the safety and efficacy of long-term Oxbryta use in SCD patients ages 12 and older. The improvements in Hb and markers of hemolysis that were observed in the HOPE study were sustained in the OLE period for patients who previously received 900 mg and 1,500 mg of Oxbryta, demonstrating a durability of response. Patients who switched from placebo to Oxbryta saw improvements in Hb levels and measures of hemolysis from the start of the OLE through week 48, consistent with the HOPE Study results.

Data from the ongoing Retrospective Study to Evaluate Outcomes in Patients with Sickle Cell Disease Treated with Oxbryta (RETRO) (Poster #3100; will be presented on December 13), the first multicenter, retrospective study to examine the real-world effectiveness of Oxbryta, showed the treatment was associated with increased Hb levels and decreased hemolytic markers. Additional findings are expected to be presented in 2022 to enable a deeper understanding of the long-term efficacy and safety of Oxbryta.

Safety data across the HOPE OLE and RETRO studies of Oxbryta were consistent with those from the Phase 3 HOPE Study of SCD patients ages 12 years and older.

Inclacumab Phase 1 Dosing Analysis in Healthy Volunteers
An analysis (Poster #977) of​ a Phase 1 study of inclacumab, GBT’s fully human P-selectin monoclonal antibody in development for the reduction of VOCs in SCD patients, showed a well-tolerated safety profile for up to 29 weeks following a single dose of 20 or 40 mg/kg in 15 healthy subjects. Plasma inclacumab exposures were dose-proportional over the dose range tested and demonstrated expected pharmacokinetics for healthy subjects, with apparent nonlinearity below approximately 10 µg/mL, suggesting target-mediated drug disposition.

Target concentration for both doses at 12 weeks was greater than the target activity threshold of 10 μg/mL, which was associated in prior studies of inclacumab with full inhibition of the formation of platelet-leukocyte aggregate (PLA), a known factor in the development of vascular lesions and cardiovascular events. The results support best-in-class potential for inclacumab at the dose of 30 mg/kg every 12 weeks in patients with SCD-related VOCs, which is the dose being studied in GBT’s two ongoing Phase 3 THRIVE (THerapy for Reduction with Inclacumab of VOC Episodes) trials (NCT04935879 and NCT04927247).

About Sickle Cell Disease
Sickle cell disease (SCD) affects more than 100,000 people in the United States,¹ an estimated 52,000 people in Europe,² and millions of people throughout the world, particularly among those whose ancestors are from sub-Saharan Africa.³ It also affects people of Hispanic, South Asian, Southern European and Middle Eastern ancestry.³ Complications of SCD begin in early childhood and can include neurocognitive impairment, acute chest syndrome, and silent and overt stroke, among other serious issues.⁴ 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.⁵ 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.^5–7 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.^6–9

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.¹⁰

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 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,¹¹ 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 Therapeutics
Global 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 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; the content, timing and significance of data and abstracts to be presented at ASH; potential future findings from RETRO, including timing and significance; 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; 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

1. 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.
2. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182125. Accessed June 12, 2020.
3. Centers for Disease Control and Prevention website. Sickle Cell Disease (SCD). https://www.cdc.gov/ncbddd/sicklecell/data.html. Accessed June 3, 2019.
4. Kanter J, et al. Blood Rev. 2013 Nov;27(6):279-87.
5. National Heart, Lung, and Blood Institute website. Sickle Cell Disease. https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease. Accessed August 5, 2019.
6. Rees DC, et al. Lancet. 2010;376(9757):2018-2031.
7. Kato GJ, et al. Nat Rev Dis Primers. 2018;4:18010.
8. Kato GJ, et al. J Clin Invest. 2017;127(3):750-760. 
9. Caboot JB, et al. Paediatr Respir Rev. 2014;15(1):17-23.
10. Oxbryta (voxelotor) tablets prescribing information. South San Francisco, Calif. Global Blood Therapeutics, Inc.; November 2019.
11. Ataga K. et al. N Engl J Med. 2017;376(5):429-439.

Contact:
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