Materia Medica

of the data did not present any differences in both safety and efficacy between these patients or the younger patients in the trial.6

Future Implications and Conclusion

Although only approved in the US for once-daily dosing for anemia of CKD in adults undergoing dialysis, other clinical trials with daprodustat have been conducted. Daprodustat has been studied and approved in Japan for anemia in patients with CKD not undergoing dialysis. The data has shown noninferiority to darbepoetin alfa for change in the Hb concentration from baseline and cardiovascular outcomes. The lack of approval for this indication is likely attributed to the higher frequency of some adverse events (cancer-related death and tumor progression/ recurrence) in patients taking daprodustat and that no other ESAs were used as comparators.8 Also, the ASCEND-D trial was extended to compare daprodustat three times weekly dosing of daprodustat to epoetin alfa, which showed noninferiority for the mean change in Hb concentration. However, the trial did not have adequate power to test cardiovascular endpoints and lacked comparison to ESAs other than epoetin alfa.9

Anemia is one of the most common complications associated with CKD. When other causes, such as nutrient deficiencies, are ruled out, anemia in these patients is likely due to kidney damage resulting in decreased EPO production. For the past 35 years, these patients have had limited options for treatment, all of which have been parenteral agents. As of February 2, 2023, there is an oral agent available. Daprodustat is the first oral agent FDA approved for adults with anemia who have been undergoing dialysis for at least four months. Data from an international trial with 2,964 participants showed that daprodustat was non-inferior to ESAs regarding the change in Hb concentration from baseline and occurrences of MACEs. Also, adverse reactions and risks associated with daprodustat were not significantly different than the comparator agents in the trial.6 Due to recent approval, daprodustat is not yet available for purchase. Additionally, GlaxoSmithKline has not released pricing or insurance coverage information.

References

1. Chronic Kidney Disease Basics. Centers for Disease Control and Prevention. https://www. cdc. gov/kidneydisease/basics.html#:~:text=disease%20(CKD).-,About%20Chronic%20Kidney%20 Disease,as%20heart%20disease%20 and%20stroke. Published February 28, 2022. Accessed February 21, 2023.

2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1-150. doi: 10.1038/ kisup.2012.73.

3. Anemia in Chronic Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney%20disease/anemia#:~:text=of%2 0renal%20disease.-,How%20common%20 is%20anemia%20in%20CKD%3F,with%20 kidney% 20disease%20have%20anemia. Published September 2020. Accessed February 21, 2023.

4. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(4):279-335. doi: 10.1038/kisup.2012.32.

5. Dhillon S. Daprodustat: First Approval. Drugs. 2020;80(14):1491-1497. doi:10.1007/s40265020-01384-y

6. Jesduvroq [package insert]. Durham, NC: GlaxoSmithKline. https://gskpro.com/content/ dam/glob al/hcpportal/en_US/Prescribing_Information/Jesduvroq/pdf/JESDUVROQ-PI-MG. PDF. Publish ed February 2023. Accessed February 21, 2023.

7. Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021;385(25):2325-2335. doi:10.1056/nejmoa2113379

8. Singh AK, Carroll K, McMurray JJV, et al. Daprodustat for the Treatment of Anemia in Patients not Undergoing Dialysis. N Engl J Med. 2021;385(25):2313-2324. doi:10.1056/ nejmoa2113380

9. Coyne DW, Singh AK, Lopes RD, et al. Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients. Clin J Am Soc Nephrol. 2022;17(9):1325-1336. doi:10.2215/ cjn.00550122

Ms. Zents is a Doctor of Pharmacy candidate at LECOM School of Pharmacy. Dr. Freedy is a Clinical Pharmacy Specialist in Medicine and Drug Information at Allegheny Health Network, Allegheny General Hospital. For any questions concerning this article, please contact Dr. Freedy at the Allegheny Health Network, Allegheny General Hospital, Center for Pharmaceutical Care, Pittsburgh, PA. (412) 359-3192 or email tucker.freedy@ahn.org