Will There Be a Role for a Short-Acting Biosimilar Erythropoiesis-Stimulating Agent in US Nephrology Practice?

Patent protection for pharmaceuticals in the United States is very robust and perhaps there is no greater example than epoetin alfa. Since the approval of epoetin alfa by the Food and Drug Administration (FDA) in 1989, the developer, Amgen (Thousand Oaks, CA), has successfully defended its patent against competing agents, such as epoetin beta (Chugai-Upjohn, Rosemont, IL), epoetin delta (Shire, Lexington, MA), and methoxy polyethylene glycol-epoetin beta (CERA; Roche, Basel, Switzerland). The US patent on epoetin alfa expired in 2015, opening the way for competition by products other than Amgen’s own darbepoetin. The first non-Amgen erythropoiesis-stimulating agent (ESA) to enter the US market was CERA, which had previously been approved by the FDA as a new drug under a biologic license application 351(a). Drugs approved through the 351(a) pathway must undergo expensive clinical testing, the cost of which is ultimately passed on to the consumer. ESAs are biologic drugs, defined by the FDA as “a virus, therapeutic serum, toxin, antitoxin, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product . . . applicable to the prevention, treatment of cure of a disease or condition of human beings.

Erythropoiesis-stimulating agents and pure red-cell aplasia: you can’t fool Mother Nature

Subtle alterations in the properties of biopharmaceutical agents may increase their immunogenicity and lead to the production of autoantibodies. Biosimilar agents may not undergo the same quality control in their production, packaging, storage, and distribution as their patented competitors. The extensive use of biosimilar erythropoiesis-stimulating agents led to an epidemic of pure red-cell aplasia in Thailand. The response of Thai regulators may be a model for other countries as the use of biosimilar agents expands

Anemia management under a bundled payment policy for dialysis: a preview for the United States from Japan

The goal of a bundled payment policy for dialysis is to decrease overall expenditures and shift financial risk from the payer to the provider. The primary target for cost reduction is invariably erythropoiesis-stimulating agents (ESAs), because of their large costs and potential for dose sparing. Japan succeeded in reducing ESA doses and maintaining stable hemoglobin levels through modest increases in intravenous iron administration. Dialysis providers in the United States have this and other strategies available

Employment among Patients on Dialysis: An Unfulfilled Promise

Comment on : Employment among Patients Starting Dialysis in the United States. [Clin J Am Soc Nephrol. 2018

Difficult Patient Behavior in Dialysis Facilities

Difficult behavior exhibited by dialysis patients is a spectrum that includes nonadherence, verbal or physical abuse, and threatening acts. Such behaviors may lead to harmful consequences to the patient, other patients, the facility, and staff and can culminate in involuntary discharge. It is important to recognize that these “difficult behaviors” may be due to underlying psychosocial or medical issues, which places an onus on care providers to explore further. According to the Conditions for Coverage (CfC) for dialysis facilities, it falls upon the medical director to coordinate and oversee policies for patient satisfaction, patient safety and rights, involuntary discharges, and adverse events and outcomes. Thus, medical directors are liable for their own actions, and their staff for which they have oversight, for harm or perceived harm to patients in response to difficult behaviors. Guidelines to deal with specific patient behavior scenarios have been published by the Decreasing Dialysis Patient Conflict National Task Force of the Forum of end-stage renal disease (ESRD) Networks. The common denominator for these difficult scenarios is impaired communication, and the majority of patient concerns involve issues with staff, policies, treatments, and diet. Involuntary discharge of a patient should always be viewed as a last resort, and there is a structured process described in the CfC that requires the involvement of the respective ESRD Network and the facility medical director. As physicians, we are bound by ethical and growing legal obligations to act in an appropriate, ethical, and fair manner to patients who are considered to be “difficult.

Recent and Emerging Therapies for Iron Deficiency in Anemia of CKD: A Review

Iron deficiency commonly contributes to the anemia affecting individuals with chronic kidney disease. This review describes diagnostic criteria for iron deficiency in chronic kidney disease, as well as mechanisms of functional and absolute iron deficiency and general treatment principles as delineated in the KDIGO (Kidney Disease: Improving Global Outcomes) guideline. Repletion of absolute iron deficits has progressed over time with the addition of better tolerated, more effective oral agents, including ferric citrate, ferric maltol, and sucrosomial iron. This article examines the structural characteristics and trial data enabling regulatory approval of these novel oral agents. Newer intravenous iron therapies, including ferric carboxymaltose and ferric derisomaltose, allow for fewer infusions and decreased risk of serious hypersensitivity reactions. Concerns about adverse effects such as cardiovascular events and infections are discussed. The potential risk of 6H syndrome (high FGF-23, hypophosphatemia, hyperphosphaturia, hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism) due to these intravenous agents is emphasized. The proposed pathophysiology of 6H syndrome and hypophosphatemia is described. Ferric pyrophosphate citrate enables administration of iron for repletion through dialysate. Relative merits, costs, and risks of various iron agents such as hypersensitivity and 6H syndrome/hypophosphatemia are summarized