GSK's HIF-PH Inhibitor Duvroq (Daprodustat): A Highly Effective and Safe Novel Oral Therapy for Renal Anemia

News on November 14, 2021 /BioValleyBIOON/ --GlaxoSmithKline PLC.(GSK) recently announced positive results from the Phase 3 ASCEND program at the 2021 American Society of Nephrology Annual Meeting — ASN Kidney Week 2021. These results confirmedDuvroq (daprodustat, Daprodustat Tablets)As a new oral therapy for the treatment of non-dialysis and dialysis chronic kidney disease (CKD) patientsAnemiaThe Potential:In non-dialysis and dialysis patients, daprodustat can improve or maintain hemoglobin (Hb) levels within the target range compared to standard care therapy, without increasing cardiovascular risk.

The active pharmaceutical ingredient in Duvroq is daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) developed for the treatment of renal anemia caused by chronic kidney disease (CKD). The ASCEND program consists of five Phase III clinical trials that evaluated the efficacy and safety of daprodustat in treating CKD-induced anemia across the entire spectrum of CKD. The program enrolled over 8,000 patients who received treatment for up to 4.26 years.

Previously released project data shows,Daprodustat achieved the primary efficacy endpoint in each study.: Improved hemoglobin (Hb) levels in untreated CKD anemia patients and maintained Hb levels in CKD anemia patients treated with erythropoiesis-stimulating agents (ESA, a standard treatment option). Additionally, two key cardiovascular outcome studies in non-dialysis patients (ASCEND-ND) and dialysis patients (ASCEND-D) showed that daprodustat was non-inferior to ESA in terms of the co-primary endpoint – risk of major adverse cardiovascular events (MACE).

Data presented at this year's ASN conference showed,Daprodustat is well-tolerated in both non-dialysis and dialysis populations.. Two key cardiovascular outcome studies (ASCEND-ND, ASCEND-D) have both met their respective primary efficacy and safety endpoints. The efficacy results of the two studies both indicate,Daprodustat treatment can improve or maintain patients' hemoglobin (Hb) levels within the target range.. In addition, the primary safety analysis results of the pre-specified intention-to-treat (ITT) population showed,Daprodustat vs ESA: Major Adverse Cardiovascular Events (MACE: all-cause mortality, non-fatalMyocardial Infarction, non-fatal stroke) incidence rates were similar.

In the ASCEND-ND trial, the hazard ratio (HR) for the time to first occurrence of MACE was 1.03 (95% CI: 0.89–1.19), demonstrating non-inferiority (pre-specified margin of 1.25). In the ASCEND-D trial, the HR for the time to first occurrence of MACE was 0.93 (95% CI: 0.81–1.07), also achieving non-inferiority (pre-specified margin of 1.25). The results from each study and across treatment groups confirmed this.Compared with the current standard treatment method, erythropoietin-stimulating agents (ESAs), daprodustat does not increase cardiovascular risk.. The most common adverse events in patients treated with daprodustat includeHypertension, diarrhea, dialysis hypotension, peripheral edema, urinary tract infection.

GSK Chief Scientific Officer and R&D President Dr. Hal Barron stated: "More than 700 million people worldwide suffer from chronic kidney disease, and approximately one in seven of these patients have anemia. Based on the scientific research of Nobel Prize winners, we believe the ASCEND program data shows that daprodustat has the potential to transform the treatment landscape for these patients."

In addition to the ASCEND-D and ASCEND-ND studies, the program also includes the incident dialysis study (ASCEND-ID) for patients who have just started dialysis, the quality of life measurement study (ASCEND-NHQ), and the thrice-weekly dosing regimen study (ASCEND-TD). Each study in the program met its respective primary or co-primary endpoints, demonstrating that daprodustat treatment can maintain hemoglobin (Hb) levels in high-risk incident dialysis patients (ASCEND-ID study), significantly improve hemoglobin (Hb) levels and quality of life in non-dialysis patients (ASCEND-NHQ study), and provide a new dosing regimen (ASCEND-TD study).

Throughout the ASCEND program, daprodustat was well-tolerated in both non-dialysis and dialysis patients. The incidence of treatment-emergent adverse events (TEAEs) was similar across the treatment groups. The most common adverse events reported in patients receiving daprodustat throughout the ASCEND program includedHypertension, diarrhea, dialysis hypotension, peripheral edema, and urinary tract infection.

Chemical Structure of Daprodustat (Source: selleck.cn)

Anemia is common in patients with chronic kidney disease (CKD) because their kidneys no longer produce sufficient amounts of erythropoietin, a hormone involved in promoting red blood cell production. Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Inhibition of oxygen-sensing prolyl hydroxylase (PH) stabilizes hypoxia-inducible factor (HIF), leading to the transcription of genes for erythropoietin and other factors involved in red blood cell production and iron metabolism, mimicking the physiological effects that occur in the body at high altitudes.

HIF-PHI is a new class of drugs that can trigger the body's adaptation to hypoxia and stimulate the bone marrow to produce more red blood cells, thereby benefiting patients with renal anemia.

Duvroq was approved in Japan in June 2020 for the treatment of renal anemia in adult patients caused by CKD.This is the world's first regulatory approval for Duvroq, which has not yet been approved in other regions. In November 2018, Kyowa Kirin and GSK signed a strategic collaboration agreement for the commercialization of Duvroq in the Japanese market. According to the terms of the agreement, following regulatory approval, Kyowa Kirin will be fully responsible for the distribution of Duvroq in Japan.

Duvroq can reduce renal anemia and benefit patients by stimulating the bone marrow to produce more red blood cells. The drug provides a convenient oral treatment option, avoiding the administration challenges and refrigeration requirements associated with injectable erythropoiesis-stimulating agents/recombinant human erythropoietin (rhEPO). In addition, Duvroq can be used in both dialysis and non-dialysis patients, offering a more convenient treatment option for renal anemia. (Bioon.com)

Source of Original Text:GSK announces positive Phase III efficacy and safety data for daprodustat in patients with anaemia due to chronic kidney disease