Comparison of Safety Reports to the FDA from a Pilot Introduction of Peginesatide, a Third Generation Erythropoiesis Stimulating Agent Versus Those from the Usual Care Setting: Manufacturers of Biosimilars and the FDA Should Consider Pilot Introductions of These Agents

Background: Thirty eight anaphylaxis cases were reported to the FDA during the first year of peginesatide marketing in 2012. Marketing was discontinued as a result. We compare 28 reports from a pilot peginesatide introduction conducted by the largest dialysis organization (LDO) in North America versus the 10 reports of anaphylaxis from usual care settings. The pilot introduction was conducted at 10 LDO centers, a nurse was assigned to each center, and staff were educated on peginesatide dosing, safety, pharmacokinetics, and handling.

Methods: Reports in the FDA of anaphylaxis occurring within 30 minutes of peginesatide administration were reviewed for information on administration site, patient characteristics, time to report to FDA, and patient outcome.

Findings: In comparison to 28 anaphylaxis events reported to the FDA from the pilot introduction (as described in Bennett CL et al NEJM 2014), 10 anaphylaxis reports to the FDA from the usual care settings were less often reported as fatal (0% versus 22%) or grade IV severity (10% versus 22%) associated with hypotension (20% versus 57%), or cardiorespiratory arrest (0% versus 29%), and were reported to the FDA later (median of 81 days (range, 14- 172) versus 46 days (range, 4 – 136 days). They were more often associated with clinical findings of diaphoresis (40% versus 18%), syncope (30% versus 18%), or angioedema (20% versus 11%). Onset was a median of four to five minutes after peginesatide infusion in either setting. Among 25,000 peginesatide-treated patients (19,430 in the pilot introduction), anaphylaxis rates were 1.4 per 1,000 persons in either setting.

Conclusion: Clinical characteristics of anaphylaxis events were more serious and FDA reporting more timely for peginesatide-associated anaphylaxis reported to the FDA from the pilot introduction versus usual care settings. With the anticipation of biosimiars in the United States, consideration should be given to requiring pilot introductions of these agents to facilitate safety assessment.