GSK Presents Optimistic CKD-Related Anemia Results Months After Rivals’ Failure

GlaxoSmithKline is lining up a potential new treatment for patients with anemia due to chronic kidney disease following positive results in a Phase III study that showed the investigational candidate improved or maintained hemoglobin levels without an increase in cardiovascular risk.

GSK’s clinical success positions the company to take the lead in this indication after the U.S. Food and Drug Administration (FDA) rejected AstraZeneca’s and FibroGen’s roxadustat in August. The Complete Response Letter called for a new clinical trial before the companies can seek approval for its oral HIF-PH inhibitor. The rejection was not a complete surprise, given the advisory committee’s thumbs down earlier in the summer over safety concerns with roxadustat.

GlaxoSmithKline’s daprodustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), hit its primary and secondary endpoints in the ASCEND-ND and ASCEND-D. GSK flexed its clinical success at the American Society of Nephrology’s Kidney Week 2021, highlighting the positive impact of the drug in both non-dialysis and dialysis settings. The company notes that daprodustat is the first oral HIF-PHI to “clearly show positive efficacy, along with no increased cardiovascular risk as assessed in the primary analysis of major adverse cardiovascular events (MACE) in the intent to treat population” compared to the current standard of care, an erythropoietin-stimulating agent, in both non-dialysis patients and dialysis patients. Additionally, the company has highlighted the studies in multiple articles in the New England Journal of Medicine.

“Over 700 million people suffer from chronic kidney disease worldwide, and an estimated 1-in-7 of these patients suffers from anemia. Grounded in research based on Nobel Prize-winning science, we believe these data show daprodustat has the potential to transform the treatment landscape for these patients, many of whom have limited treatment options today,” said GSK’s Chief Scientific Officer and President of Research and Development Dr. Hal Barron in a statement.

In both the ASCEND-ND and the ASCEND-D trials, daprodustat not only demonstrated that it could improve or maintain hemoglobin levels within the targeted range, but it also showed that it is non-inferior to standard-of-care treatments, which are typically Epogen or Aranesp.

According to GSK, so far, data from five Phase III studies have demonstrated that daprodustat improved or maintained hemoglobin within target levels without increased cardiovascular risk when compared to standard of care. The clinical program includes more than 8,000 patients who received treatment for more than four years.

Ajay Singh, M.D., a nephrologist and principal investigator of the ASCEND studies, said the data from these studies show that daprodustat can potentially be a transformative treatment for patients with anemia due to chronic kidney disease.

“I think these are ground-breaking results and show that daprodustat has potential to be transformative for these patients. The ASCEND program was designed to represent anemia management in practice today, and these results provide strong clinical evidence to help nephrologists as they make the right treatment decisions for their patients,” said Singh, who is also the senior associate dean for Postgraduate Medical Education at Harvard Medical School.

Daprodustat was well tolerated in both non-dialysis and dialysis populations as assessed in the primary analysis.