Riastap (fibrinogen concentrate, human) Public Summary of Risk Management Plan (Extract from the EU Risk Management Plan Version 3.

Transcription

1 Riastap (fibrinogen concentrate, human) Public Summary of Risk Management Plan (Extract from the EU Risk Management Plan Version 3.1; 14 Apr 2016)

2 VI.2 VI.2.1 Elements for a Public Summary Overview of Disease Epidemiology Fibrinogen is a protein in the blood that is required for normal blood clotting. Patients can be affected by fibrinogen disorders that are present from birth (ie, congenital) or which develop after birth (ie, acquired). Congenital Fibrinogen Disorders Fibrinogen disorders that are present at birth are rare inherited bleeding disorders due to lack of fibrinogen, low fibrinogen levels or non-functioning fibrinogen. It is estimated that 1 in every million individuals is affected with a lack of fibrinogen. Disorders due to low fibrinogen levels or non-functioning fibrinogen are more common, although the actual number of people affected is unknown because many patients remain undiagnosed. Lack of fibrinogen is associated with moderate to severe bleeding after minor injuries or minor surgery, and is often diagnosed in newborns due to umbilical cord bleeding. Low fibrinogen levels and non-functioning fibrinogen are associated with fewer bleeding episodes and are sometimes only diagnosed after traumatic events or surgery. Fibrinogen disorders that are present from birth affect similar numbers of men and women, but there is little information regarding geographical differences. Replacement of fibrinogen, using fibrinogen concentrate, is the recommended treatment of bleeding in these patients. Acquired Fibrinogen Deficiency Fibrinogen disorders that develop after birth can be due to multiple causes, including severe infections, trauma, complications of childbirth, or major surgery associated with bleeding. These disorders are usually associated with massive blood loss and disruption of normal blood clotting. There is little information regarding the number of people affected by fibrinogen disorders that develop after birth. In England and Wales, from 2001 to 2014, the number of hospital admissions associated with potential acquired fibrinogen deficiency was estimated at 22 cases in every hospital admissions. The majority of admissions were due to excessive blood loss after surgery or childbirth, and as such, admissions were twice as common in women as in men. Replacement of fibrinogen, using blood products that contain variable quantities of fibrinogen (eg, fresh frozen plasma, cryoprecipitate) or fibrinogen concentrate, is the most widely used treatment of bleeding in these patients. Page 2 of 6

3 VI.2.2 Summary of treatment benefits Congenital fibrinogen disorders Treatment benefits with fibrinogen concentrate, human (FCH) in these patients have been demonstrated in 2 studies, the first of which involved 15 patients. The impact of FCH on blood clotting was assessed by measuring maximum clot firmness after treatment with FCH; maximum clot firmness was significantly higher 1 hour after treatment with FCH compared with before treatment. The second study determined how well FCH either stopped a bleeding event or prevented excessive bleeding during surgery. Records from FCH-treated patients with lack of fibrinogen (8 patients), low fibrinogen levels (3 patients), and non-functioning fibrinogen (1 patient), describing 26 bleeding episodes and 11 surgeries, were reviewed. FCH treatment was judged by a doctor as good, moderate, or poor. The ability of FCH to stop bleeding was assessed as good for all 26 bleeding episodes and the ability of FCH to prevent excessive surgical bleeding was assessed as good for 10 surgeries and moderate for 1 surgery. Acquired fibrinogen deficiency Treatment benefits with FCH in these patients have been demonstrated in a study that investigated how well FCH prevented excessive bleeding during surgery involving a major heart blood vessel. Sixty-one patients participated in the study; 29 patients treated with FCH and 32 patients with placebo (ie, fake treatment). Patients treated with FCH had a reduced need for blood products (approximately 2 units each) compared with placebo patients (approximately 13 units each). Thirteen patients, all of whom were treated with FCH, did not require a blood transfusion. Another study investigated how well FCH could control bleeding during complex heart surgery. A total of 152 patients participated in the study; 78 patients treated with FCH and 74 patients with placebo. Results from this study were inconclusive in that the transfusion requirements of patients treated with FCH (approximately 5 units) were not significantly different from those of patients treated with placebo (approximately 3 units). These results were likely due to numerous differences in study conduct across study centers in different countries. VI.2.3 Unknowns Relating to Treatment Benefits Information regarding the use of FCH in patients < 16 years, 65 years, and patients of non-caucasian ethnic origin are limited. There is no evidence to suggest that treatment benefits would be any different in these patient populations. Page 3 of 6

4 VI.2.4 Summary of Safety Concerns Important identified risks Risk What is known Preventability Blood clots that can block blood vessels (thromboembolic events) Allergic reactions (hypersensitivity) These events are very rare and may affect the arteries or veins. Blood clots occurring in the veins may lead to a painful swelling of the legs (deep vein thrombosis) and occasionally, life threatening or fatal clots in the lungs or brain. Clots in the arteries may lead to a heart attack or stroke particularly in people who already have problems with their arteries. These are rare and unwanted effects that may occur during treatment. Symptoms range from mild (burning or stinging at the injection site, chills, flushing or rashes) to severe (shock that leads to death). If an allergic reaction occurs, the treatment has to be stopped immediately and the person has to be treated appropriately according to the kind and severity of reaction. Partially, by using FCH in accordance with the directions in the package insert Partially, by avoiding use in people with known allergies to fibrinogen or to any of the other components in FCH. Important potential risks Risk The medicine could contain a virus or other infectious agents What is known (Including reason why it is considered a potential risk) FCH is made from human plasma. When medicines are made from human blood or plasma, several steps are taken to prevent infections from being passed on to people treated with the medicine. These steps include: Carefully selecting blood and plasma donors to make sure donations are not taken from anyone who may have an infection. Testing each donation for signs of viruses. Treating the blood and plasma during the manufacturing process to inactivate or remove any viruses that might be present. Despite all these steps, when people are treated with medicines prepared from human blood or plasma, the possibility of passing on a virus or infectious agent cannot be excluded. Page 4 of 6

5 Missing information Risk Limited information on the safety of FCH during pregnancy and in breastfeeding mothers Limited information on the safety of FCH in children Limited information on the safety of FCH in the elderly Use of FCH for a disease or condition it is not approved for What is known FCH has not been tested in women who are pregnant. It is not known if FCH can cause harm to the fetus. FCH has not been tested in women who are breastfeeding. It is not known if FCH can cause harm to the baby. Since human fibrinogen is a normal constituent of human blood, treatment of the nursing mother with fibrinogen is not expected to present a risk to the breastfed newborn / infant. Patients should talk to their doctor before becoming pregnant. FCH has been tested in very few children less than 16 years, however, there is no indication that the safety-related effects in younger patients are different from that of adults. FCH should only be used in children if clearly needed. FCH has been tested in very few elderly patients, however, there is no indication that safety-related effects in the elderly differ from that of adults < 65 years. FCH is recommended to be used only for the conditions it is approved for. VI.2.5 Summary of Risk Minimisation Measures by Safety Concern All medicines have a Summary of Product Characteristics which provides physicians, pharmacists and other health care professionals with details on how to use the medicine, the risks and recommendations for minimising them. An abbreviated version of this in lay language is provided in the form of the package leaflet. The measures in these documents are known as routine risk minimisation measures. The Summary of Product Characteristics and the Package leaflet for Riastap and Haemocomplettan P are based on the Company Core Data Sheet (CCDS) as the Reference Safety Information. The relevant CCDSs and Company Core Package Insert for RiaSTAP and Haemocomplettan P can be found in the European Public Assessment Reports. Approved national Labelling Texts are available upon request. RiaSTAP and Haemocomplettan P do not have special conditions and restrictions for its safe and effective use (additional risk minimisation measures). This medicine has no additional risk minimisation measures. Page 5 of 6

6 VI.2.6 Planned Post Authorisation Development Plan List of studies in post authorisation development plan Study/activity (including study number) Study BI Objectives Efficacy and safety of FCH in patients undergoing thoracic aortic aneurysm repair with cardiopulmonary bypass Safety concerns /efficacy issue addressed Ability to reduce the number of units of allogeneic products transfused in the 24 hours subsequent to study product administration Status Completed 2015 Date for submission of (interim and) final results Studies that are a condition of the marketing authorisation Study BI3023_3001 was a condition of the marketing authorisation in the United States and in the European Union (EU), to show a connection between maximum clot firmness and the clinical benefit of FCH in patients with congenital fibrinogen disorders. Study BI3023_3001 was determined by CSL Behring to not be feasible to conduct, as sites were unable to enrol a single subject in over 4 years despite all efforts made. CSL Behring has subsequently closed study BI3023_3001 and has initiated an alternate study: BI3023_4003. Study BI3023_4003, initiated in April 2015, is a retrospective study of patients with congenital fibrinogen deficiency who primarily obtained FCH through the Special Access Program in Canada. In addition to the retrospective data, patients are followed for 12 months in an observational, prospective portion of the study. VI.2.7 Summary of Changes to the Risk Management Plan Over Time A summary of major changes to the Risk management Plan over time is provided in Table 19. Table 19: Major changes to the Risk Management Plan over time Version Date Safety Concerns Comment 2 17-Feb-2014 No change on safety concerns 3 18-Sep-2015 No change on safety concerns Apr-2016 No change on safety concerns First edition of the Safety Risk Management Plan according to the new GVP format, only submitted to Romania Inclusion of the results of study BI3023_3002 Removal of one placebo case, which was included by error in the verum group in section Part II, Module SVII Page 6 of 6