Second of three pivotal studies intended to support regulatory filing in Japan in 2019
LONDON, UK I October 29, 2018 I GSK today announced the results from a randomised, double blind, active-controlled phase 3 study in Japanese patients to evaluate daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, as a potential treatment for anaemia associated with chronic kidney disease (CKD).
Results from the 52-week study of 271 haemodialysis-dependent patients, showed that oral daprodustat met its primary endpoint of non-inferiority to darbepoetin alfa IV injection, as measured by mean haemoglobin levels over Weeks 40 to 52.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said, “Anaemia is common in patients with chronic kidney disease and can result in symptoms such as weakness and fatigue. The promising data generated from this study is an important step in the development of daprodustat as a potential oral treatment option for these patients.”
The safety profile was consistent with that observed in the previous studies of daprodustat[i],[ii] and across all treatment arms. The percentage of patients who experienced at least one on-therapy adverse event was 93% in the daprodustat group and 97% in the control group. The most common adverse events across the treatment groups were nasopharyngitis (42% daprodustat and 54% control), gastrointestinal events (46% daprodustat and 46% control), and shunt stenosis (14% daprodustat and 15% control).
Results from this study are part of the ongoing Phase 3 programme being conducted in Japan to support submission to the Japanese Ministry of Health, Labour and Welfare in 2019. Positive results from the first phase 3 study were presented at the American Society of Nephrology’s Kidney Week in October 2018. Results from the final Japan study in non-dialysis dependent patients are anticipated in 1H2019.
Global development programme
In addition to the Japan programme, GSK has an ongoing global Phase 3 registration programme, including:
- ASCEND-D (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis) will enrol approximately 3,000 dialysis dependent patients with anaemia associated with CKD switching from an erythropoietin-stimulating agent (ESA). Recruitment has completed, and results are anticipated in 2020
- ASCEND-ND (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis) will enrol approximately 4,500 non-dialysis dependent patients with anaemia associated with CKD, and will include patients either switching from or naive to an ESA. Recruitment remains ongoing and results are anticipated in 2020.
For both studies, the co-primary endpoints are time to first occurrence of major adverse cardiovascular events (MACE) and mean change in haemoglobin between the baseline and efficacy period (mean over Weeks 28-52). The studies will assess whether daprodustat is non-inferior to recombinant human erythropoietin and its analogues on these endpoints as the primary analysis. If non-inferiority of the primary analysis is met, superiority will be assessed for the MACE endpoint.
About daprodustat
Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. Inhibition of oxygen-sensing prolyl hydroxylase enzymes stabilises hypoxia-inducible factors, which can lead to transcription of erythropoietin and other genes involved in the production of red blood cells and iron metabolism, similar to the physiological effects that occur in the body at high altitude. Daprodustat is not approved as a treatment for anaemia or any other indication anywhere in the world.
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Principal risks and uncertainties in the company’s Annual Report on Form 20-F for 2017.
[i] Holdstock L, Meadowcroft AM, Maier R et al. Four-week studies of oral hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 for treatment of anemia. J Am Soc Nephrol 2016; 27: 1234–1244
[ii] Amy M Meadowcroft, Borut Cizman, Louis Holdstock, Nandita Biswas, Brendan M Johnson, Delyth Jones, A Kaldun Nossuli, John J Lepore, Michael Aarup, Alexander R Cobitz; Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants on hemodialysis, Clinical Kidney Journal 2018 sfy014, https://doi.org/10.1093/ckj/sfy014
SOURCE: GlaxoSmithKline
Post Views: 22
Second of three pivotal studies intended to support regulatory filing in Japan in 2019
LONDON, UK I October 29, 2018 I GSK today announced the results from a randomised, double blind, active-controlled phase 3 study in Japanese patients to evaluate daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, as a potential treatment for anaemia associated with chronic kidney disease (CKD).
Results from the 52-week study of 271 haemodialysis-dependent patients, showed that oral daprodustat met its primary endpoint of non-inferiority to darbepoetin alfa IV injection, as measured by mean haemoglobin levels over Weeks 40 to 52.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said, “Anaemia is common in patients with chronic kidney disease and can result in symptoms such as weakness and fatigue. The promising data generated from this study is an important step in the development of daprodustat as a potential oral treatment option for these patients.”
The safety profile was consistent with that observed in the previous studies of daprodustat[i],[ii] and across all treatment arms. The percentage of patients who experienced at least one on-therapy adverse event was 93% in the daprodustat group and 97% in the control group. The most common adverse events across the treatment groups were nasopharyngitis (42% daprodustat and 54% control), gastrointestinal events (46% daprodustat and 46% control), and shunt stenosis (14% daprodustat and 15% control).
Results from this study are part of the ongoing Phase 3 programme being conducted in Japan to support submission to the Japanese Ministry of Health, Labour and Welfare in 2019. Positive results from the first phase 3 study were presented at the American Society of Nephrology’s Kidney Week in October 2018. Results from the final Japan study in non-dialysis dependent patients are anticipated in 1H2019.
Global development programme
In addition to the Japan programme, GSK has an ongoing global Phase 3 registration programme, including:
- ASCEND-D (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis) will enrol approximately 3,000 dialysis dependent patients with anaemia associated with CKD switching from an erythropoietin-stimulating agent (ESA). Recruitment has completed, and results are anticipated in 2020
- ASCEND-ND (Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis) will enrol approximately 4,500 non-dialysis dependent patients with anaemia associated with CKD, and will include patients either switching from or naive to an ESA. Recruitment remains ongoing and results are anticipated in 2020.
For both studies, the co-primary endpoints are time to first occurrence of major adverse cardiovascular events (MACE) and mean change in haemoglobin between the baseline and efficacy period (mean over Weeks 28-52). The studies will assess whether daprodustat is non-inferior to recombinant human erythropoietin and its analogues on these endpoints as the primary analysis. If non-inferiority of the primary analysis is met, superiority will be assessed for the MACE endpoint.
About daprodustat
Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. Inhibition of oxygen-sensing prolyl hydroxylase enzymes stabilises hypoxia-inducible factors, which can lead to transcription of erythropoietin and other genes involved in the production of red blood cells and iron metabolism, similar to the physiological effects that occur in the body at high altitude. Daprodustat is not approved as a treatment for anaemia or any other indication anywhere in the world.
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Principal risks and uncertainties in the company’s Annual Report on Form 20-F for 2017.
[i] Holdstock L, Meadowcroft AM, Maier R et al. Four-week studies of oral hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 for treatment of anemia. J Am Soc Nephrol 2016; 27: 1234–1244
[ii] Amy M Meadowcroft, Borut Cizman, Louis Holdstock, Nandita Biswas, Brendan M Johnson, Delyth Jones, A Kaldun Nossuli, John J Lepore, Michael Aarup, Alexander R Cobitz; Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants on hemodialysis, Clinical Kidney Journal 2018 sfy014, https://doi.org/10.1093/ckj/sfy014
SOURCE: GlaxoSmithKline
Post Views: 22
