LONDON, November 5, 2021 / PRNewswire / – GlaxoSmithKline plc (LSE / NYSE: GSK) today announced the positive results of the phase III program ASCEND (Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a novel prolyl hydroxylase inhibit Daprodustat) for daprodustat, a investigational drug inducible by oral hypoxia factor prolyl hydroxylase inhibitor (HIF-PHI), presented at the American Society of Nephrology’s Kidney Week 2021. The main positive efficacy and safety results confirm the potential of daprodustat as a new oral therapy for patients with chronic kidney disease (CKD) anemia in non-dialysis and dialysis settings. Daprodustat was developed on the basis of unique Nobel Prize winning science which demonstrated how cells sense and adapt to the availability of oxygen.

The ASCEND program includes five phase III studies evaluating the efficacy and safety of daprodustat for the treatment of anemia due to CRF throughout the course of CRF. The program recruited over 8,000 patients who were treated for up to 4.26 years. Daprodustat was well tolerated in non-dialysis and dialysis populations, as assessed in the primary analysis. Data on daprodustat, including the results of the two pivotal Phase III studies focusing on non-dialysis patients (ASCEND-ND) and dialysis patients (ASCEND-D), were shared at the meeting of the American Society of Nephrology during a last-minute combined oral presentation. The results for ASCEND-ND and ASCEND-D were also published simultaneously in the New England Journal of Medicine.

The ASCEND-ND and ASCEND-D studies each met their primary efficacy and safety criteria. Efficacy results from the two phase III studies demonstrated that daprodustat improved or maintained patients within their target hemoglobin (Hb) range. In addition, the results of the predefined primary safety analysis of the intention-to-treat (ITT) population showed similar rates of major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction. non-fatal or non-fatal stroke. independently in each test. In the ASCEND-ND trial, results showed a risk ratio reflecting time to first onset of MACE of 1.03; 95% CI (0.89 to 1.19), reaching non-inferiority with the predefined margin of 1.25. In the ASCEND-D trial, results showed a risk ratio reflecting the time to first onset of MACE of 0.93; 95% CI, (0.81-1.07), reaching non-inferiority with the predefined margin of 1.25. Results from each study and across all treatment arms confirmed that there was no increased cardiovascular risk for daprodustat compared to an erythropoietin-stimulating agent (ESA), the current standard of care.

The most frequently reported adverse events in patients receiving daprodustat included hypertension, diarrhea, hypotension due to dialysis, peripheral edema, and urinary tract infection.

Daprodustat is the first oral HIF-PHI to clearly show positive efficacy, without increased cardiovascular risk as assessed in the primary analysis of MACE in the ITT population compared to ESA, both in non-dialysis patients and dialysis patients.

Dr. Hal barron, Scientific Director and President, R&D, GSK, said: “More than 700 million people suffer from chronic kidney disease worldwide, and it is estimated that one in seven patients has anemia. Based on Nobel Prize-winning science-based research, we believe these data show that daprodustat has the potential to transform the treatment landscape for these patients, many of whom today have limited treatment options. “

In addition to the primary analysis of the ITT population, several additional additional analyzes were performed for the ASCEND-ND and ASCEND-D trials. Further details can be found in the New England Journal of Medicine publications (here and here).

Data from three additional trials under the ASCEND program provided additional support for the use of daprodustat. The ASCEND-TD trial showed positive efficacy results when administered three times per week, in addition to the once daily regimen evaluated in the ASCEND-ND and ASCEND-D studies, providing supporting data additional dosage options for daprodustat. Additional results demonstrated that treatment with daprodustat resulted in a significant improvement over placebo in Hb levels and quality of life in non-dialysis patients by measurement of the SF-36 vitality score (as determined by the fatigue level) in the ASCEND-NHQ trial, as well as the ability to maintain Hb levels in the high-risk incident dialysis population in the ASCEND-ID trial.

Dr. Ajay Singh, Nephrologist / Principal Investigator, Chairman of the Executive Steering Committee and ASCEND Program Steering Committee and Senior Associate Dean for Postgraduate Medical Education, Harvard Medical School, said: “As a nephrologist who regularly treats patients with anemia due to chronic kidney disease, I believe these results are revolutionary and show that daprodustat has the potential to transform these patients. The ASCEND program was designed to represent the management of anemia in practice. today, and these results provide strong clinical evidence to help nephrologists make the right treatment decisions for their patients. ”

Sir Peter J. Ratcliffe, professor of medicine, Oxford University, Francis Crick Institute and Nobel Laureate, said, “Derived from decades of research into how cells sense and adapt to oxygen availability, it is extraordinary to see how this work has translated into positive clinical evidence within the ASCEND program. The data shared today demonstrates the importance of following the science and how a better understanding of the body’s natural responses enables us to create drugs that can have a significant impact on the lives of patients. “

Daprodustat is currently approved in Japan like Duvroq for patients with renal anemia. It is not approved anywhere else in the world. The results of the phase III ASCEND program will be used to support regulatory filings with health authorities around the world.

Notes to Editors:

Results of ASCEND-ND and ASCEND-D trials

• ASCEND-ND (Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis) included 3,872 non-dialysis dependent patients with CRF-associated anemia who have switched from standard therapy (ESA) or are not currently receiving treatment to receive daprodustat or ESA Control (darbepoetin alfa). Iron management protocols were instituted in both arms of the study. The study met its primary endpoints for safety and efficacy. The results showed that daprodustat improved and / or maintained the Hb within the target level (10-11.5 g / dL) for these patients, and the primary safety analysis of the ITT population showed that daprodustat achieved non-inferiority compared to ASE control.
• ASCEND-D (Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis) included 2,964 dialysis patients with anemia associated with CKD who were transferred to receive daprodustat or ESA control from standard ESA therapy. A uniform iron management protocol was instituted in both arms of the study. The study met its primary endpoints for safety and efficacy. The results showed that daprodustat improved or maintained Hb within the target levels (10-11.5 g / dL) for these patients, and the primary safety analysis of the ITT population showed that daprodustat reached non-inferiority compared to ESA control.

About CKD Anemia
Chronic kidney disease (CKD), characterized by progressive loss of kidney function, is a growing global public health burden.^I Risk factors for CRF include hypertension, diabetes, obesity, and primary kidney disease.i Additionally, CRF is an independent risk factor for cardiovascular disease.i Anemia is a significant complication and frequent IRC.ⁱⁱ However, it is often misdiagnosed and undertreated in patients with early-stage CRF, such as those not on dialysis.ii When left untreated or undertreated, anemia due to CRF is associated with poor clinical outcomes and results in substantial burden on patients and health systems.ii

About daprodustat
Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PHI) inhibitor, belongs to a new class of oral drugs indicated for the treatment of anemia due to chronic renal failure (CRF) in adult patients. not on dialysis and dialysis. Inhibition of oxygen-sensitive prolyl hydroxylase enzymes stabilizes factors inducible by hypoxia, which can lead to the transcription of erythropoietin and other genes involved in the correction of anemia, similar to physiological effects that occur in the body at high altitudes. Daprodustat was developed to provide a convenient oral treatment option for patients with anemia associated with CRF.

About GSK
GSK is a science-driven global healthcare company. For more information, please visit www.gsk.com/about-us.

Caution Regarding Forward-Looking Statements
GSK cautions investors that all forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties which may cause actual results to differ materially from those projected. These factors include, but are not limited to, those described in the company’s annual report on Form 20-F for 2020, GSK’s third quarter results, and any impact from the COVID-19 pandemic.

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^I Hill NR, Fatoba ST, Oke JL, et al. Global prevalence of chronic kidney disease – A systematic review and meta-analysis. PLoS A. 2016; 11 (7): e0158765.
ⁱⁱ St Peter WL, Guo H, Kabadi S, et al. Prevalence, Treatment Patterns, and Health Care Resource Utilization in Medicare and in Non-Dialysis Dependent Chronic Kidney Disease Patients With and Without Anemia under Commercial Insurance. United States. BMC Nephrol. 2018; 19 (1): 67.

SOURCE GlaxoSmithKline plc

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