Archived Policies - Prescription Drugs
Human Fibrinogen Concentrate (RiaSTAP)
Human fibrinogen concentrate, pasteurized (HFCP) (RiaSTAP ™) may be considered medically necessary for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency (CFD) Factor I bleeding disorder, including afibrinogenemia and hypofibrinogenemia, when the following criteria are met:
All other use of human fibrinogen concentrate (RiaSTAP ™) is considered experimental, investigational and unproven, including but not limited to dysfibrinogenemia.
Fibrinogen deficiency affects only 150 to 300 people in the United States and is usually diagnosed at birth when newborns bleed from their umbilical cord site. Individuals with CFD are unable to make sufficient amounts of fibrinogen (also called Factor I), which is a protein that plays an important role in blood coagulation by helping to form blood clots and prevent bleeding. Fibrinogen is manufactured in the liver and circulates in the blood plasma in a normal concentration of 250-400 mg/dL. Symptoms of CFD include excessive bleeding following an injury; bruising; spontaneous bleeding; and bone, joint, and tissue hemorrhage, in addition to the excessive bleeding at the umbilical cord site.
On January 16, 2009, the FDA approved human fibrinogen concentrate, pasteurized (HFCP) (RiaSTAP ™), a concentrated form of human fibrinogen (coagulation Factor I), as an orphan drug for the treatment of bleeding in patients with a rare genetic defect known as CFD.
HFCP, made from the pooled plasma of healthy human blood donors, is for patients who have no fibrinogen or abnormally low levels, known as afibrinogenemia. Additional HFCP is made for those patients, whose fibrinogen levels fall below 50 mg/dL, known as hypofibrinogenemia. The FDA approval label states HFCP is not indicated for those patients having dysfibrinogenemia, in which the patient may have normal fibrinogen levels, but defective fibrinogen function.
Abnormal bleeding times are identified via laboratory blood coagulation testing or blood clotting factor assays, which includes the following:
Additional testing may be completed to evaluate all aspects of a blood clotting disorder.
An orphan drug is defined in the 1984 amendments of the Orphan Drug Act as "a drug intended to treat a condition affecting fewer than 200,000 persons in the United States or will not recover development cost, plus a reasonable profit, within seven years following FDA approval. The Orphan Drug Act was signed into law on January 4, 1983."
HFCP is administered intravenously, with dosages based upon measured fibrinogen levels. To date, there are no other concentrated fibrinogen product is available in the United States. HFCP is manufactured by CSL Behring GmbH, Marburg, Germany and distributed by CSL Behring LLC, Kankakee, Illinois.
The FDA orphan product designation was based upon a study of 15 patients with afibrinogenemia who achieved the target level of fibrinogen expected to prevent bleeding after they received 70 milligrams/kilograms of the drug. In addition, plasma from 14 of the 15 patients showed increased maximum clot firmness, a surrogate marker likely to predict clinical benefit.
This was a phase II multinational, multicenter (ten centers in the United States and Italy), prospective, open-label, and uncontrolled design clinical trial, conducted in subjects with CFD manifested as afibrinogenemia, in a non-bleeding state. Of the 15 subjects, ten were males, with 11 in an age range of 16 to <65 years and the balance between 8 and 14 years. Plasma fibrinogen activity and antigen screening had to be undetectable (<20 mg/dL). HFCP was administered as a single intravenous infusion of 70 milligram/kilogram body weight. Blood samples were drawn at pre-dose and at 0.5, 1, 2, 4, 8, 24, 96, 144, 216, and 312 hours post-dosing. Fourteen patient’s laboratory results were evaluated (one subject’s plasma samples thawed during transport). The pharmacokinetics of HFCP, in terms of plasma fibrinogen activity and antigen screening, indicate that HFCP has a long half-life and is slow clearance drug. The results indicated no difference between females and males. In children younger than 16 years, the half-life and clearance of HFCP were 11% shorter and 32% faster than in adults. However, due to the small study size of children younger than 16 years, it is difficult to make any outright conclusion.
Clinical trials will be conducted in the United Kingdom to determine whether HFCP has a role in major vascular surgery to reduce the necessity of blood component transfusions. Additional phase III clinical trials are being completed in the United States as part of the FDA OPD approval process.
Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.
The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.
A national coverage position for Medicare may have been developed or changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.
Kreuz, W., Meili, E., et al. Efficacy and tolerability of a pasteurized human fibrinogen concentrate in patients with congenital fibrinogen deficiency. Transfusion and Apheresis Science (2005 June) 32(3):247-53.
Negrier, C., Rothschild, C., et al. Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen concentrate. Journal of Thrombosis and Haemostatis (2008 September) 6(9);1494-9.
Acharya, S.S., and D.M. Dimichele. Rare inherited disorders of fibrinogen. Haemophilia (2008 November) 14(6):1151-8.
Tziomalos, K., Vakalopoulou, S., et al. Treatment of congenital fibrinogen deficiency: overview and recent findings. Vascular Health and Risk Management (2009) 5:843-8.
FDA – RiaSTAP (human fibrinogen concentrate, pasteurized) – Product Information, Label, Approval Letter, News Release. Food and Drug Administration (2009 January 16). Available at <http://www.fda.gov> (accessed – 2009 November 10).
Rahe-Meyer, N., Pichlmaier, M., et al. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study (2009 June) 102(6):785-92.
Fenger-Erikson, C., Ingerslev, J., et al. Fibrinogen concentrate – a potential universal hemostatic agent. Expert Opinion on Biological Therapy (2009 October) 9(10):1325-33.
1/1/2010 New medical document. Human Fibrinogen Concentrate (RaiSTAP ™) may be considered medically necessary when criteria are met for treatment of Factor I bleeding disorder (congenital fibrinogenemia).
|Title:||Effective Date:||End Date:|
|Human Fibrinogen Concentrate (RiaSTAP)||04-15-2017||09-14-2018|
|Human Fibrinogen Concentrate (RiaSTAP)||04-01-2016||04-14-2017|
|Human Fibrinogen Concentrate (RiaSTAP)||01-01-2015||03-31-2016|
|Human Fibrinogen Concentrate (RiaSTAP)||08-01-2012||12-31-2014|
|Human Fibrinogen Concentrate (RiaSTAP)||01-01-2010||07-31-2012|