GlaxoSmithKline recently announced positive headline results from five studies of the Phase III ASCEND program conducted with George Clinical evaluating the efficacy and safety profile of daprodustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for patients with anemia due to chronic kidney disease (CKD).
The ASCEND program showed that daprodustat met its primary efficacy endpoint in each study, demonstrating an improvement in hemoglobin (Hgb) levels in untreated patients and maintaining Hgb levels in patients treated with an erythropoietin stimulating agent (ESA), a standard treatment option, in patients with anemia of CKD. In addition, the key cardiovascular outcomes studies for non-dialysis (ASCEND-ND) and dialysis patients (ASCEND-D) demonstrated that daprodustat was non-inferior when compared to an ESA in the risk of major adverse cardiovascular events (MACE), the co-primary endpoint of both studies.
“The positive results from these long and complex ASCEND studies, with which George Clinical teams have been involved in for the past several years, are important for our industry, kidney and metabolic practitioners and those suffering from CKD around the world,” said Chief Medical Officer Maria Ali.
George Clinical was involved in steering committee management for the studies with scientific leader Dr. Vlado Perkovic on the executive steering committee since the beginning of the program which included the major effort of organizing all steering committee meetings for the duration of the program and managing their logistics, members and oversight responsibilities.
Global scientific leadership from George Clinical participated across the many countries involved in this enormous program. These committees were led by Zuhaib Baig of project operations, as the global project lead with support from several George Clinical operations team members as well as fellow scientific leaders Dr. Muh Geot Wong and Dr. Inna Kolesnyk.
The organization also led global endpoint adjudication in collaboration with Duke Clinical Research Institute through Shenshen Li and Jen Than of medical and safety services, which represents one of the most compelling accomplishments of endpoint adjudication from the global George Clinical team.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK, said, “I am particularly pleased with the results from the ASCEND-ND and ASCEND-D studies given the importance of managing cardiovascular outcomes for patients who are currently suffering from anemia due to chronic kidney disease, as well as the need to provide a convenient, oral treatment option. We will continue to analyze the data from the robust Phase III ASCEND program and look forward to working closely with regulators as we plan for our submissions.”
In addition to the ASCEND-D and ASCEND-ND studies, the program also included studies focused on incident dialysis, for patients just starting dialysis (ASCEND-ID); quality of life measures (ASCEND-NHQ); as well as three-times weekly dosing regimens (ASCEND-TD). Each of the studies from the program met its respective primary or co-primary endpoint(s). The program enrolled more than 8,000 patients who were treated for up to 3.75 years. The full results of the studies will be presented at a forthcoming medical meeting later this year and will be used to inform regulatory pathways with health authorities worldwide.
Chronic kidney disease, characterized by progressive loss of kidney function, is an increasing global public health burden. Risk factors for CKD include hypertension, diabetes, obesity and primary renal disorders. Furthermore, CKD is an independent risk factor for cardiovascular disease. Anemia is an important and frequent complication of CKD. However, it is often poorly diagnosed and undertreated in patients with early-stage CKD, such as those not on dialysis. When left untreated or undertreated, anemia of CKD is associated with poor clinical outcomes and leads to a substantial burden on patients and healthcare systems.