In January 2009, the US Food and Drug Administration (FDA) approved CSL Behring’s RiaSTAP™ for the treatment of acute bleeding episodes in people with congenital fibrinogen deficiency, a rare bleeding disorder also known as factor I deficiency. RiaSTAP, which has status as an orphan drug, is the first FDA-approved treatment for this condition. Orphan drugs are drugs or biologics used to treat a rare disease or condition affecting fewer than 200,000 patients in the United States; all clotting factors are eligible. Manufacturers of orphan drugs receive tax incentives and longer periods of marketing exclusivity.
Factor I deficiency, or congenital fibrinogen deficiency, includes three rare coagulation disorders: afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia. Afibrinogenemia and hypofibrinogenemia involve the absence or low levels of fibrinogen. Dysfibrinogenemia occurs when the fibrinogen does not work well. Because fibrinogen is needed for most types of platelet aggregation—the clumping together of platelets in the blood—people with factor I deficiency can have a combined bleeding disorder. This occurs when both platelets and clotting are abnormal. According to the FDA, factor I deficiency affects 150–300 people in the US. It is usually diagnosed at birth when newborns bleed from their umbilical cord site. Other symptoms include bruising; joint, bone and tissue bleeds; and excessive bleeding following an injury.
RiaSTAP is approved to treat acute bleeds in people with afibrinogenemia, who have no fibrinogen or low levels of it. It is also approved for people with hypofibrinogenemia whose fibrinogen levels are below 50 mg/dL. RiaSTAP is not approved for people with dysfibrinogenemia, who may have normal fibrinogen levels but defective fibrinogen function; these individuals are at risk for both bleeding and clotting complications. RiaSTAP is contraindicated for people who have had severe immediate hypersensitivity reactions, including anaphylaxis to it or its components.
“This product offers a much-needed treatment for the small number of patients with congenital fibrinogen deficiency,” says Jesse Goodman, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research. “If bleeding occurs in the brain or other organs and is left untreated, it may lead to blood loss, organ damage and death.”
RiaSTAP is an intravenous fibrinogen concentrate made from the pooled plasma of healthy human blood donors. According to CSL Behring, the drug undergoes viral inactivation and removal for safety assurance. The FDA approval is based on data from a Phase II study of 15 patients with afibrinogenemia who reached the target level of fibrinogen expected to prevent bleeding after receiving 70 mg/kg of the drug. Plasma from 14 of the 15 patients also showed increased maximum of clot firmness, a marker the FDA believes is likely to predict clinical benefit.
Chills, fever, headache and nausea and vomiting were the most common adverse reactions that were observed. Postmarketing studies will include patients with afibrinogenemia and hypofibrinogenemia.