Press Release
GBT Announces Updated 24-Week Efficacy Data from All Patients Enrolled in Phase 3 HOPE Study Showing Statistically Significant and Sustained Improvements in Hemoglobin with Voxelotor
Data Supporting the Potential of Voxelotor as a Disease-Modifying Treatment for Sickle Cell Disease
(SCD) Published in
Symposium at the 24th
Additional Clinical Data Supporting Voxelotor Program in SCD
also Presented at EHA 2019
Company to Host Corporate Update Webcast, Today,
at
Transcranial Doppler Study
The data were published today in
“These additional data from our multi-national, Phase 3 HOPE Study support and strengthen the 24-week findings from 154 patients that were presented at the
“These positive data from more than 270 patients enrolled in the HOPE Study provide strong evidence that voxelotor, by significantly improving anemia and hemolysis, has the potential to be a disease-modifying treatment for SCD by preventing chronic organ damage and prolonging survival,” said Jo Howard, MB BChir, MRCP, FRCPath, of Guy’s and St. Thomas’
New HOPE Study Results Show Robust Improvements in Anemia with Voxelotor (Abstract #S147)
The new results from the HOPE Study include 24-week efficacy data from 274 patients ages 12 and older with SCD enrolled in the study from 60 institutions across 12 countries. The data showed that patients treated with once-daily oral voxelotor demonstrated rapid, robust and sustained improvements in anemia, as measured by the increase in hemoglobin from baseline to 24 weeks compared to placebo (see Table 1). The mean increase in hemoglobin levels with voxelotor compared to placebo was similar with or without concurrent hydroxyurea treatment.
These results from the HOPE Study are reported using both intention-to-treat (ITT) and per-protocol (PP) analyses. The PP analysis is based on patients who completed the primary endpoint visit of 24 weeks, whereas the more conservative ITT analysis defines all patients with missing data at 24 weeks as non-responders. Previously, GBT had reported HOPE Study results as assessed only in the PP population. As discussed with the
Table 1
Intention-To-Treat (ITT) Analysis | Per-Protocol (PP) Analysis | |||||
N | % with >1 g/dL Increase in Hb |
Mean* Change in Hb from Baseline to 24 Weeks |
N | % with >1 g/dL Increase in Hb |
Mean Change in Hb from Baseline to 24 Weeks |
|
1500 mg voxelotor |
90 | 51.1% (p<0.001) |
1.1 g/dL (p<0.001) |
74 | 59.5% (p<0.001) |
1.3 g/dL (p<0.001) |
900 mg voxelotor |
92 | 32.6% (p<0.001) |
0.6 g/dL (p<0.001) |
79 | 38.0% (p<0.001) |
0.7 g/dL (p<0.001) |
Placebo | 92 | 6.5% | -0.1 g/dL | 76 | 9.2% | 0 g/dL |
*Adjusted for baseline stratification factors. P-value is for comparison versus placebo; not adjusted for multiplicity. |
The ITT analysis of all 274 patients at 24 weeks showed:
- Hemoglobin improved rapidly from baseline to the earliest timepoint measured (2 weeks) with voxelotor 1500 mg and was sustained through 24 weeks (p<0.001 vs. placebo). The improvement in hemoglobin was similar in patients with or without background use of hydroxyurea.
- Voxelotor 1500 mg increased hemoglobin levels to a mean of 9.8 g/dL at 24 weeks from a baseline of 8.6 g/dL, consistent with a clinically meaningful improvement in anemia.
- Improvements from baseline in hemoglobin, percent reticulocytes and indirect bilirubin occurred with both voxelotor doses, further demonstrating an improvement in hemolysis consistent with a dose-related inhibition of hemoglobin polymerization.
- There were numerically fewer vaso-occlusive crises (VOCs) and a lower annualized incidence rate (per person-year) of VOCs in both voxelotor dose groups than in the placebo group, despite the significant increases in hemoglobin with voxelotor treatment.
- Voxelotor was generally safe and well tolerated, with both doses having similar safety profiles. Treatment discontinuation rates did not differ substantially among the three trial groups. There was no evidence of impairment of tissue oxygenation at either dose of voxelotor.
Additional data presented in poster sessions at the 2019
- Clinical data from an investigator-initiated ancillary study of three adolescents with SCD enrolled in the HOPE-KIDS 1 Study showed that all participants had unchanged or lower cerebral blood flow as measured by functional MRI with angiography while receiving voxelotor, suggesting that cerebral blood flow was maintained or improved with administration of voxelotor. Lower cerebral blood flow with rising hemoglobin levels suggests improved oxygen delivery to the brain. (Abstract #PF740)
- An in vitro study of the mechanism of voxelotor showed that oxygen is released from voxelotor-modified hemoglobin under deoxygenated conditions and that normal physiological compensatory mechanisms to enhance oxygen delivery are not disrupted. This finding suggests that treatment with voxelotor maintains oxygen delivery to tissues and supports the safety of this investigational treatment. (Abstract #PS1522)
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About Sickle Cell Disease
SCD is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, which leads to the formation of abnormal hemoglobin known as sickle hemoglobin (HbS). In its deoxygenated state, HbS has a propensity to polymerize, or bind together, forming long, rigid rods within a red blood cell (
About Voxelotor in Sickle Cell Disease
Voxelotor (previously called GBT440) is being developed as an oral, once-daily therapy for patients with SCD. Voxelotor works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes voxelotor blocks polymerization and the resultant sickling and destruction of red blood cells. With the potential to improve hemolytic anemia and oxygen delivery, GBT believes that voxelotor may potentially modify the course of SCD. In recognition of the critical need for new SCD treatments, the
GBT is currently evaluating voxelotor in the HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study, a Phase 3 clinical study in patients age 12 and older with SCD. Additionally, voxelotor is being studied in the ongoing Phase 2a HOPE-KIDS 1 Study, an open-label, single- and multiple-dose study in pediatric patients (age 4 to 17) with SCD. The HOPE-KIDS 1 Study is assessing the safety, tolerability, pharmacokinetics and exploratory treatment effect of voxelotor.
About GBT
GBT is a clinical-stage biopharmaceutical company determined to discover, develop and deliver innovative treatments that provide hope to underserved patient communities. GBT is developing its lead product candidate, voxelotor, as an oral, once-daily therapy for sickle cell disease. 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 about GBT’s development plans for voxelotor and the potential benefits of voxelotor for SCD patients and other statements containing the words “anticipate,” “planned,” “believe,” “forecast,” “estimated,” “expected,” and “intend,” among others. These forward-looking statements are based on GBT’s current expectations and actual results could differ materially. 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 our plan to submit an NDA for voxelotor under an accelerated regulatory approval pathway, the availability of, and sufficiency of our data to support, accelerated regulatory approval, the therapeutic potential and safety profile of voxelotor, including the potential to be a disease-modifying therapy for SCD, our plan to initiate a TCD confirmatory study, the potential for TCD flow velocity to serve as an acceptable primary endpoint in a confirmatory study, the potential for voxelotor to become a new standard of care for treating adolescents and adults with SCD, our ability to implement and complete our clinical development plans for voxelotor, the potential for an increase in hemoglobin of 1 g/dL or greater to reduce the risk of stroke and mortality in patients with SCD, our ability to generate and report data from our ongoing and potential future studies of voxelotor (including data from patients enrolled in our Phase 3 HOPE Study, and data from our ongoing Phase 2a HOPE-KIDS 1 Study), regulatory review and actions relating to voxelotor, our potential commercial launch of voxelotor, and the timing of these events, 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 results of clinical trials may be subject to differing interpretations, 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, that drug-related adverse events may be observed in clinical development, and that data and results may not meet regulatory requirements or otherwise be sufficient for further development, regulatory review or approval, along with those risks set forth in our Annual Report on Form 10-K for the fiscal year ended
Contact Information:
Stephanie Yao (investors & media)
GBT
+1-650-741-7730
media@gbt.com
Source: Global Blood Therapeutics, Inc.