CSL Behring announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for RiaSTAP™, the first and only treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Congenital fibrinogen deficiency is a rare, potentially life-threatening bleeding disorder that affects an estimated one person per million, with an estimated prevalence in the U.S. of approximately 300 patients. RiaSTAP is not indicated to treat dysfibrinogenemia.
RiaSTAP was granted orphan status in March 2008 and priority review in August 2008. Approval was based on a pivotal phase II prospective, open-label pharmacokinetic (PK) and safety study using maximum clot firmness (MCF) as a surrogate endpoint for hemostatic efficacy. MCF is a laboratory measure of the structural integrity of the clot, reflecting the underlying effectiveness of the fibrinogen present to form a fibrin clot.
"The FDA approval of RiaSTAP underscores CSL Behring’s ongoing commitment to addressing the unmet needs of patients with rare and serious bleeding disorders," said Robert Lefebvre, General Manager and Vice President of CSL Behring’s U.S. Commercial Operations. "As a leader in developing safe, effective and high-quality biologic therapies, CSL Behring is pleased to introduce a product for congenital fibrinogen deficiency that provides a new therapeutic option to support hemostasis and clot stability."
Fibrinogen, also called Factor I (one), is a protein needed to form a blood clot. Fibrinogen levels in plasma determine the potential clotting ability and activity in the body. Diminished concentrations of fibrinogen limit the body’s ability to form a clot. Certain fibrinogen levels usually indicate normal blood clotting ability, though in rare instances a person can have a normal quantity of fibrinogen that does not function as needed.
Symptoms of congenital fibrinogen deficiency include excessive bleeding following injury, bruising, bleeding of the umbilical cord at birth and from the site of the umbilical stump in a newborn, spontaneous bleeding and bone, joint or tissue hemorrhage. To determine fibrinogen levels and confirm a diagnosis, blood coagulation testing is needed.
“RiaSTAP marks a significant improvement in the treatment of congenital fibrinogen deficiency,” said Dr. Marilyn Manco-Johnson, Professor of Pediatrics and Director, Mountain States Regional Hemophilia and Thrombosis Center. “Now patients with this rare bleeding disorder have access to an effective, safe and convenient therapy that has been available in Europe for years. CSL Behring’s development of RiaSTAP for the U.S. market exemplifies the company’s dedication to and support of the rare bleeding disorder community.”
RiaSTAP is a purified fibrinogen concentrate that undergoes virus inactivation and removal for safety assurance. There have been more than 1 million units sold worldwide (marketed outside the U.S. under the trade name Haemocomplettan® P).
Results from the 15-patient PK study showed that median fibrinogen plasma antigen levels and median fibrinogen plasma activity levels reached a maximum within 30 minutes (antigen) to 1 hour (activity) post-infusion and decreased continuously afterward. Results also demonstrated a highly significant (p<0.0001) mean improvement in MCF from baseline to 1 hour post-infusion following RiaSTAP treatment.
CSL Behring is studying RiaSTAP in an ongoing post-marketing commitment study to further demonstrate safety and hemostatic efficacy.
“Safety at the Source”
CSL Behring owns and operates more than 70 plasma collection centers in the U.S. and Europe, applying high standards to the collection process. Before qualifying as a donor, each candidate undergoes a series of health checks, including a family history. Donated plasma is subjected to a series of serological tests that go beyond regulatory requirements. Before fractionation, the plasma pool is further tested by nucleic acid testing for viral markers to ensure the maximum possible level of safety for patients. Additionally, virus inactivation and removal occur during the manufacturing process through heat treatment and precipitation steps.
RiaSTAP is a purified fibrinogen concentrate indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. RiaSTAP is not indicated for dysfibrinogenemia. RiaSTAP is contraindicated in individuals who have had severe immediate hypersensitivity reactions, including anaphylaxis to RiaSTAP or its components.
Physicians should monitor patients for early signs of allergic or hypersensitivity reactions and if necessary, discontinue administration and institute appropriate treatment. Thrombotic events have been reported in patients receiving RiaSTAP. Physicians should weigh the benefits of administration versus the risks of thrombosis.
RiaSTAP is made from pooled human plasma. Products made from human plasma may contain infectious agents (e.g., viruses and theoretically the Creutzfeldt-Jakob disease agent (CJD) that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing. Despite these measures, such products may still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products.
The most serious adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic-anaphylactic reactions and thromboembolic episodes, including myocardial infarction, pulmonary embolism, deep vein thrombosis and arterial thrombosis. The most common adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic reactions and generalized reactions such as chills, fever, nausea and vomiting.
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About CSL Behring
CSL Behring is a global leader in the plasma protein biotherapeutics industry. Passionate about improving the quality of patients' lives, CSL Behring manufactures and markets a range of safe and effective plasma-derived and recombinant products and related services. The company's therapies are used in the treatment of immune deficiency disorders, hemophilia, von Willebrand disease, other bleeding disorders and inherited emphysema. Other products are used for the prevention of hemolytic diseases in the newborn, in cardiac surgery, organ transplantation and in the treatment of burns. The company also operates one of the world's largest plasma collection networks, ZLB Plasma. CSL Behring is a subsidiary of CSL Limited, a biopharmaceutical company with headquarters in Melbourne, Australia. For more information, visit www.cslbehring.com.
Sheila A. Burke, Director, Communications & Public Relations
Worldwide Commercial Operations