ZymoGenetics, Inc, announced the submission of a Citizen Petition to the US Food and Drug Administration (FDA) requesting that the FDA remove Thrombin-JMI Thrombin, topical (bovine origin) from the market in the interest of patient safety. The Citizen Petition is prompted by recent reports of serious or fatal bleeding-related adverse events in surgical patients exposed to bovine (cattle-derived) thrombin.
"Serious adverse events, including death, linked to bovine thrombin continue to be reported to the FDA," said George Rodgers, professor of Medicine and Pathology at the University of Utah, and medical director of the Coagulation Laboratory at ARUP Laboratories. "These adverse events are a serious, ongoing safety issue for patients undergoing surgery."
The petition notes that because bovine thrombin is recognized by the body as a foreign protein, and bovine thrombin preparations contain low levels of other coagulation proteins found in cattle plasma, these products prompt an immune response (formation of antibodies) in a substantial portion of patients exposed to them. In some patients, these antibodies may interfere with the coagulation process and consequently cause coagulation abnormalities; this condition is called immune-mediated coagulopathy (IMC).
Effects of IMC can range from lab abnormalities to severe bleeding and, in some cases, death. The FDA-approved prescribing information for topical bovine thrombin notes that the risk of antibody formation increases with multiple exposures, and that patients with pre-existing antibodies to bovine thrombin preparations should not be re-exposed to these products. However, clinicians do not have access to a readily available diagnostic test to screen for these antibodies, and patients are not likely to know whether they have previously been exposed to bovine thrombin.
The petition states that more than 25 cases of patients developing IMC after exposure to bovine thrombin preparations have been published since 2000 in the medical literature, representing a wide range of surgical settings and adult and paediatric patients. The adverse events reported in published case reports have ranged from asymptomatic laboratory abnormalities to serious adverse events including severe haemorrhage, thrombosis, and death.1 Publications by independent experts highlight the relationship between exposure to bovine thrombin preparations and the development of IMC.
The petition asserts that the body of evidence from the contemporary medical literature, combined with ongoing spontaneous adverse event reports to FDA, indicate that IMC is a continuing safety risk associated with bovine thrombin, warranting action by FDA. In the past few years, FDA has approved alternative human thrombin products not derived from cattle plasma, including one made by ZymoGenetics. The petition asserts that the risks associated with use of Thrombin-JMI outweigh the benefits. ZymoGenetics can provide no assurance that the petition will be granted or that Thrombin-JMI will be removed from the market.
ZymoGenetics is focused on the creation of novel protein drugs to improve patient care and address unmet medical needs.