KEEP LIFE FLOWING
Kedrion’s plasma-derived therapies help people suffering from debilitating conditions like Hemophilia and Immune Deficiencies. We are privileged to provide this service and do so with a profound sense of responsibility.
KEEP LIFE FLOWING
Kedrion’s plasma-derived therapies help people suffering from debilitating conditions like Hemophilia and Immune Deficiencies. We are privileged to provide this service and do so with a profound sense of responsibility.
KEEP LIFE FLOWING
Kedrion’s plasma-derived therapies help people suffering from debilitating conditions like Hemophilia and Immune Deficiencies. We are privileged to provide this service and do so with a profound sense of responsibility.
Kedrion Biopharma is an international biopharmaceutical company based in Italy that collects and fractionates plasma to produce and distribute worldwide plasma-derived products for the prevention and treatment of rare and debilitating diseases and conditions such as Hemophilia, Primary Immunodeficiencies and Rh sensitization.
Kedrion operates in Germany through its subsidiary Kedrion Biopharma GmbH offering a portfolio of medicines and licensed products to treat Immunology and Intensive care and Transplantation patients.
Kedrion was established in Italy in 2001, but the roots of the companies from which it was born stretch back several decades in the production of blood and plasma derived products. A primarily family-owned business, it places a high value not only on the welfare of those who benefit from its products but also on the people and communities where it operates.
Kedrion around the world
market presence in about 100 countries. In addition, it has acquired collection and production capacity as well as the rights to significant products for treating hemophilia and preventing Rh sensitization, a condition which can lead to Hemolytic Disease of the Fetus and the Newborn (HDFN).
Kedrion produces and distributes human plasma-derived medicinal products used to treat and prevent rare and debilitating diseases and disorders.
leading position in Italy and to increase its share of the international market. It works to strengthen its role as the accredited partner of the medical, scientific and institutional communities.
Kedrion’s ambition is to enhance its worldwide role as a strategic partner of the national health systems of those countries which aim to become self-sufficient in the availability of plasma-derived products, also via technology transfer.
Quality and Safety
As a result of its solid and successful experience as partner with the Italian Health System, its significant expansion into international operations and a fundamental commitment to research and development, Kedrion’s line of plasma-derived products is broad and diverse.
With treatments for many rare and debilitating diseases and conditions from hemolytic disease in newborns to immune deficiencies to hemophilia, Kedrion offers a wide and expanding array of treatments and therapies.
IMMUNOLOGY / NEUROLOGY
INTENSIVE CARE & TRANSPLANTATION
Our continuing commitment to research, development and innovation aims to meet the therapeutic needs of the largest number of patients living with a rare disease or debilitating condition across the world.
Below the list of Kedrion products distributed in Germany (updated March 2022).
Rare diseases are serious, often chronic and progressive, diseases. There are thousands of rare diseases. To date, six to seven thousand rare diseases have been discovered and new diseases are regularly described in medical literature. The number of rare diseases also depends on the degree of specificity used when classifying the different entities/disorders. Until now, in the field of medicine, a disease is defined as an alteration of the state of health, presenting as a unique pattern of symptoms with a single treatment. Whether a pattern is considered unique depends entirely on the level of definition of our analysis.
For many rare diseases, symptoms and signs may be observed at birth or in childhood, as is the case of Hemophilia and Primary Immunodeficiencies.
Hemophilia is a congenital bleeding disorder that results in the blood failing to clot normally. It is caused by a deficiency of a protein in the blood called a clotting factor. People with hemophilia bleed easily and often excessively. Untreated, hemophilia can be life-threatening. There are two main types of hemophilia: “Hemophilia A” is the most common type and is caused by the deficiency of what is known as Clotting Factor VIII; “hemophilia B” is caused by deficiency of Clotting Factor IX.
Hemophilia occurs in about 1 in 10,000 births and it is much more common in males because it is an “X-linked” disorder. The number of affected persons worldwide is estimated to be about 400,000. Hemophilia A is more common than hemophilia B, representing 80-85% of all cases.
Hemophilia should be suspected in patients presenting with a history of:
- Easy bruising in early childhood.
- Spontaneous bleeding (bleeding for no apparent/known reason), especially into the joints, muscles, and soft tissues.
- Excessive bleeding following trauma or surgery.
A definitive diagnosis depends on a blood analysis to determine deficiency of Clotting Factor VIII or IX.
Because each type of Hemophilia requires a different therapy, accurate diagnosis is essential.
Hemophilia can be very successfully managed by simply replacing the deficient clotting factor. Therapy can be either “on demand” – the treatment of active bleeding, or “prophylactic” – regular maintenance of clotting factor levels to prevent bleeding. In developed countries where these factors are readily available, the life expectancy of males suffering from Hemophilia is essentially the same as for males in the general population.
Both clotting factors can be isolated from donated human plasma and they can also be engineered by means of recombinant DNA technology. There are many commercial brands from which to choose and that choice is generally made based on availability, access, price and on the risk of developing antibodies that render the factor ineffective.
Srivastava A. et al. Guidelines for the management of Hemophilia. Haemophilia (2012), 1–47.
Mannucci PM et al. How we choose factor VIII to treat Hemophilia. Blood (2012) volume 119, number 18, 4108-4114
The most common bleeding disorder is von Willebrand disease (VWD). It is congenital and caused by deficiency or abnormality in a plasma protein central to blood clotting known as the von Willebrand Factor (named after the Finnish physician who first identified the disorder).
Von Willebrand Factor (VWF) is the “glue” that helps platelets in the blood stick together with the vessel wall, to form a clot where a blood vessel has been ruptured. It also binds and stabilizes the clotting factor Factor VIII, so in patients with VWD, the lack of VWF activity results in premature elimination of Factor VIII in the circulation, thereby resulting in a dual defect in the body’s ability to stop bleeding. People with VWD produce normal amounts of Factor VIII, but with deficient VWF the clotting factor does not stay in the system long enough to adequately carry out its function, as in patients with type 1 and III VWD.
There are three generally recognized forms of the disease:
- Type I: The most common and mildest form of Von Willebrand Disease. Levels of von Willebrand Factor are lower than normal, and levels of Factor VIII may also be reduced.
- Type II: In this form of Von Willebrand Disease, there is normal and sufficient Von Willebrand Factor but it is abnormal and does not work properly. The abnormality in the factor can vary and accordingly there are several subtypes of Type II Von Willebrand Disease – important to determine because treatment varies with the subtype.
- Type III: The most severe form of Von Willebrand Disease in which VWF is nearly or completely absent along with very low levels of Factor VIII.
People with Von Willebrand Disease can bruise easily; suffer frequent nosebleeds that can be difficult to stop; have heavy menstrual bleeding; and experience heavier and longer than normal bleeding after injury, surgery, childbirth, or dental work. In its most severe form, it can lead to spontaneous joint and organ bleeding and can be life-threatening.
Some patients respond favorably to injection of desmopressin acetate (DDAVP) but the most effective treatment and prophylaxis for VWD – especially in its more severe forms – is therapy with plasma-derived Von Willebrand Factor products.
Federici AB. Classification and clinical aspects of von Willebrand disease. In: Textbook of Haemophilia 2nd Edition, Lee CA, Berntorp E, Hoots K (eds). Oxford: Wiley-Blackwell 2010. 302–308.
Disorders of the Immune System fall generally in three categories:
- Overactive or inappropriate immune response.
- Deficient immune response.
- Autoimmune (self-attacking) response.
- Asthma and allergies are examples of an overactive immune system reacting to a non-threatening foreign substance.
- Immune deficiencies (Immunodeficiencies) and autoimmune disorders are generally more serious and can be life-altering.
When one of the parts of the immune system is missing or does not work well, we say that the immune system is deficient. Most often this involves missing or defective T- or B-lymphoctyes or inadequate production of antibodies. The result is that the body is vulnerable to infections that might otherwise be easily defeated.
Immunodeficiencies can be “Primary”, i.e., present at birth and usually genetic, or “Secondary”. Secondary Immunodeficiencies have many causes, including disease, malnutrition, aging, certain medications, chemo- and radiation therapy, and stress. Probably the most well-known cause of immunodeficiency, though not the most common, is the Human Immunodeficiency Virus (HIV), which can cause AIDS (Acquired Immune Deficiency Syndrome).
There are some 185 Primary Immunodeficiencies recognized by the World Health Organization. Most common are those involving the production of antibodies and are called Primary Antibody Deficiencies (PAD’s). These disorders vary greatly in their underlying defects, but many of them can be managed and their symptoms mitigated by regular infusions of Immunoglobulin.
Kedrion’s ongoing research and development has resulted in several Immunoglobulin therapies for these conditions. Replacement therapy with Immunoglobulin in Primary Antibody Deficiencies increases life expectancy and reduces infection frequency and severity.
Abbas K. et al. “Le basi dell’Immunologia. Fisiopatologia del sistema immunitario”. Ed. Masson Elsevier 2006.
The human body can sometimes become its own worst enemy. For reasons still not fully understood the human immune system can lose some of its ability for distinguishing between self and non-self and begin attacking normal healthy cells in the body. This is a condition known as Autoimmune Disease.
There are many Autoimmune Diseases that affect millions of people and their incidence seems to be growing worldwide.
The following Autoimmune Diseases are ones for which intravenous Immunoglobulin (IVIg) therapy is indicated and approved:
- Idiopathic Thrombocytopenic Purpura (ITP). Also known as Immune Thrombocytopenic Purpura or Autoimmune Thrombocytopenic Purpura, ITP is an autoimmune bleeding disorder resulting when the immune system attacks its own blood platelets, which are important to the clotting process. For reasons not well understood, lymphocytes produce antibodies that attach to the platelets, which then do not clot effectively and are subsequently recognized as “foreign” and destroyed in the spleen. Frequent and abnormal bleeding is typical and often results in many small bruises that can look like a rash (purpura). Children are generally affected with an acute form of the disorder that resolves spontaneously in a few months while in adults it is usually a chronic condition requiring long term treatment. The disease is rare, with an incidence of 3 cases per 100,000 inhabitants per year in those aged under 16 years and 1.6 to 2.68 cases per 100,000 inhabitants per year in adults, with a slight female preponderance.
Navarro RP et al.; Considerations for the Optimal Use of Immunoglobulin. Am J Manag Care. 2012;18:S67-S78
Abrahamson PE. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol..2009 Aug;83(2):83-9.
- Kawasaki Disease. Also known as Mucocutaneous Lymph Node Syndrome, is a form of vasculitis characterized by inflammation of blood vessels throughout the body. It primarily affects children under the age of five (and rarely over the age of eight).
With proper treatment the prognosis for these children is good, but without treatment about a quarter of them will develop cardiac problems, including coronary artery aneurysms. Kawasaki Disease has become the leading cause of acquired heart disease in children in the developed world.
The cause of Kawasaki Disease is still unknown with researchers divided on whether it is an infection or an autoimmune response, but effective treatment includes Primarily Intravenous Immunoglobulin.
Uehara R, Belay ED. “Epidemiology of Kawasaki disease in Asia, Europe, and the United States” J Epidemiol 2012; 22 (2): 79-85
Takahashi K et al.; Pathogenesis of Kawasaki disease. Clinical and Experimental Immunology, 2011; 164 (Suppl. 1): 20–22
Newburger JW. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114:1708–1733
This is a rare (affecting just 1-2 people in 100,000) Autoimmune Disease in which the immune system attacks the myelin or outer covering of nerves (and sometimes the nerves themselves) of the Peripheral Nervous System. The damage leads to tingling and weakness in the legs and can proceed to even life-threatening paralysis.
Symptoms generally reach their most severe within days or weeks when they stabilize for a period of days, weeks or even months. Most people recover from even the most severe cases, but recovery can take as little as a few weeks or as much as a few years. The cause of the autoimmune response is unknown but it is sometimes triggered by infection, surgery or vaccination.
One treatment for Guillain-Barré syndrome that can reduce symptoms and hasten recovery is high dose Immunoglobulin therapy.
Chronic Inflammatory Demyelinating Polyneuropathy
CIDP can be thought of us a chronic form of the Autoimmune Disorder Guillain-Barré syndrome caused by demyelination of peripheral nerves, resulting in loss of sensation, motor weakness, and sensory symptoms.
Its estimated prevalence ranges from 0.8 to 8.4 per 100,000 people. CIDP is often disabling with over 50% of patients having temporary disability and about 10% eventually becoming persistently disabled or dying because of the disease.
The cause of CIDP remains unknown, but there are data supporting an immune pathogenesis. Plasmapheresis (plasma exchange), oral corticosteroids and Intravenous Immunoglobulin (IVIg) therapy are effective treatments, but should be started early to avoid permanent nerve damage.
Pithadia AB et al.; Guillain-Barre syndrome (GBS). Pharmacological Report 2010; 62: 220 – 232
Köller H et al.; Chronic inflammatory demyelinating polyneuropathy. N Engl J Med.2005 Mar 31;352(13):1343-56.
Mahdi-Rogers M et al.; Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins. Biologics. 2010 Mar 24;4:45-9.
E. Nobile Orazio. Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial. Lancet Neurol 2012; 11 (6): 493-502
Mother and Child Health
Our Mother and Child Health area focuses on Hemolytic Disease of the Fetus and Newborn and on vertical (mother to child) transmission of Hepatitis B.
These are serious and debilitating diseases, which represent a real threat to the fetus or newborn and, in the most severe cases, can lead to death.
Nowadays both diseases are easily preventable through the screening of all pregnant women – to detect situations at risk – and the eventual administration of a correct prophylaxis.
However, despite the existence of an effective and non-invasive treatment, access to therapy is still scarce or lacking in many countries worldwide.
Maternal-fetal red cell antigen incompatibility can lead to alloimmunization, maternal Immunoglobulin transplacental transfer, and Hemolytic Disease of the Fetus and Newborn (HDFN).
Hemolytic Disease of the Fetus and Newborn (HDFN), also called Erythroblastosis Fetalis, is a condition that can arise when a mother and her unborn child have different and incompatible blood types. If even a few of the fetus’s red blood cells cross over the placenta and get into the mother’s circulation during the pregnancy, they are recognized by her immune system as “foreign” and it will produce antibodies to attack them. If these antibodies cross back over into the fetus, they will begin to destroy fetal red blood cells.
Since it takes time for antibodies to develop, the first child might not be seriously affected, but the mother’s immune system will now be sensitized to these incompatible red blood cells and subsequent pregnancies involving similar incompatibility will be seriously threatened.
The most serious type of HDFN is the one caused by Rh incompatibility in which the mother has Type Rh Negative blood and the fetus, Rh Positive. Although HDFN can be extremely serious, it is rare and preventable.
Passive Immunization with anti-D antigen Immune Globulin protects Rh(D)-negative women from sensitization against Rh(D)-positive red blood cells.
The use of Routine Antenatal Anti-D Prophylaxis (RAADP) has sharply decreased the incidence of and mortality from HDFN due to RhD allosensitization. However, despite the advent of anti-Rh(D) immunoglobulin prophylaxis, severe morbidity and death because of Rh disease have only been reduced by approximately 50% globally during the last 50 years.
Visser et al. The continuing burden of Rh disease 50 years after the introduction of anti-Rh(D) immunoglobin prophylaxis: call to action. Am J Obstet Gynecol. 2019 Sep;221(3):227.
Liumbruno et al. The role of antenatal immunoprophylaxis in the prevention of maternal-foetal anti-Rh(D) alloimmunisation. Blood Transfus 2010; 8:8-16
Bowman JM. Controversies in Rh prophylaxis: who needs Rh immune globulin and when should it be given? Am J Obstet Gynecol 1985; 151: 289-94.
Clarke CA, Donohoe WTA, McConnell RB, et al. Further experimental studies on the prevention of Rh haemolytic disease. Br Med J 1963; 1: 979-84.
Women HBV positive can transmit HBV to their babies. In areas endemic for HBV, such as Western Pacific Region and Africa, up to 20% of the general population is chronically infected, with perinatal/neonatal and childhood infections existing as a primary route for expanding the reservoir of carriers.
Chronic HBV infection, even if asymptomatic for decades, can result in eventual death from cirrhosis and hepatocellular carcinoma (HCC). Mother-to-child transmission of HBV has been associated with an increased risk of HCC. Consequently, in Asian and African countries with a high incidence of perinatal and early childhood infection, death from cirrhosis or HCC (more than half due to HBV infection) is common, among the top ten causes of death. Thus, from the outset, prevention of chronic infection in children has been a key component of HBV immunization strategies.
The currently recommended practice to reduce mother-to-child HBV vertical transmission relies on the administration of HBV vaccine and concurrent administration of hepatitis B immune globulin (HBIG) at the time of or shortly after birth. A small but growing body of data suggests that maternal treatment with NA therapy in the third trimester of pregnancy in addition to vaccine and HBIG for the infant may also reduce HBV transmission to the infant.
Silverman, N, Glob. libr. women’s med.,ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10181.
Lee C., Gong Y., Brok J. et al. Effect of hepatitis B immunization in newborn infants of mothers positive for HBsAg: systematic review and meta-analysis, BMJ 2006;332:328-336
Beasley R.P. Rocks along the road to the control of HBV and HCC. Ann Epidemiology 2009;19:231-234 Red Book, current version 2018-2021
Guidelines For The Prevention, Care And Treatment Of Persons With Chronic Hepatitis B Infection, Who, March 2015
Intensive Care and Transplantation
Intensive care, also called critical care, is the close monitoring and treatment given to patients with acute, life-threatening illness or injury such as shock, burns, accidents, sepsis, severe breathing problems and complex surgery as liver transplantation.
Chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection remains a major global health problem affecting an estimated 350 million people worldwide with more than 786000 individuals dying annually due to complications of CHB, including cirrhosis and liver cancer. CHB is the leading cause of hepatocellular carcinoma (HCC) accounting for at least 50% of newly diagnosed cases. Furthermore, HCC is the third leading cause of cancer-related mortality in the world with a dismal 5-year survival and the fastest growing rate of cancer death in North America.
Liver transplantation (LT) is the most effective treatment in patients with CHB-related liver failure, cirrhosis and HCC. However, HBV reactivation following LT emerges as a major clinical challenge. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival.
Before its introduction, reinfection with HBV after transplantation occurred in more than 80% of recipients and the 5-year graft and patient survival rates were only 50%. Now, with the use of the HBIg/nucleoside/nucleotide analogue prophylaxis, transplant programs in North America and Europe can expect prevention of HBV recurrence in greater than 90% of their patients.
Hepatitis B is contagious, but it can be transmitted from mothers to infants at the time of birth. This transmission can be markedly reduced by the immediate postpartum administration of HBIg to the infant either alone or, as currently recommended, concomitant administration of hepatitis B vaccine.
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273.e1. [PMC free article] [PubMed] [Google Scholar]
Durantel D, Zoulim F. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. J Hepatol. 2016;64:S117–S131. [PubMed] [Google Scholar]
Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, Henley SJ, Holtzman D, Lake A, Noone AM, et al. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122:1312–1337. [PMC free article] [PubMed] [Google Scholar]
Song GW, Ahn CS, Lee SG, Hwang S, Kim KH, Moon DB, Ha TY, Jung DH, Park GC, Kang SH, et al. Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin. Transplant Proc. 2014;46:3548–3553. [PubMed] [Google Scholar]
Nair S, Perrillo RP. In: BoyerTD, ed: Hepatology (4th edn). Philadelphia: Saunders, 2003: 959.
Realdi G, Fattovich G, Hadziyannis S, et al. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action onViral Hepatitis (EUROHEP). J Hepatol 1994; 21: 656^666.
Arianeb Mehrabi, “The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation” Langenbeck’s Archives of Surgery June 2012, Volume 397, Issue 5, pp 697-710.
American Academy of Pediatrics. Hepatitis B. In: Peter G, editor. 1997 Red Book. Report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1997. pp. 247–260.
Albumin is the most abundant circulating protein in the human body, making up about 50% of the total plasma protein content.
Albumin has been the first plasmaprotein produced from human plasma for therapeutic use. The scientific evidence of recent years has clearly shown that albumin is endowed with a long series of clinically relevant functions: alongside the well-known oncotic power, albumin performs many other activities that are grouped under the definition of non-oncotic properties. These include : Binding , Transport and detoxification, Antioxidant action, Modulation of the inflammatory and immunological response, Antithrombotic action, Capillary permeability and endothelial stabilization, Adjustment of acid-base balance.
The oncotic activity, together with the long circulating half-life and total half-life make albumin an excellent plasma expander, which is currently the main reason for its use in clinical practice expecially in critical situations. The non-oncotic activities play an important therapeutic role in many medical conditions where the condition of deficient plasma volume is associated with a pro- inflammatory state as in liver cirrhosis, sepsi/septic shock, burns.
All these properties makes albumin an important medicine for many clinical conditions for which other fluids are either contro-indicated or have no important therapeutic effect.
Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology 2005; 41:1211–1219.
Fanali G, Di Masi A, Trezza V, et al. Human serum albumin: from bench to bedside. Mol Aspects Med 2012; 33: 209-90.
Vincent J-L, Russell JA, Jacob M, et al. Critical Care 2014;18:231-41
Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology 2013; 58:1836-46.
Taverna M, Marie AL, Mira JP, Guidet B. Specific antioxidant properties of human serum albumin. Ann Intensive Care. 2013
Schött U, Solomon C, Fries D, Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review. Scand J Trauma Resusc Emerg Med. 2016 Apr 12;24:48.
Antithrombin is a plasma protein that inactivates Thrombin, a plasma enzyme that is important in the clotting process. Antithrombin therefore acts as a powerful anticoagulant and is used to treat acquired antithrombin deficiency from Disseminated Intravascular Coagulation (DIC) as the result of sepsis, multiple trauma, severe burns, pregnancy complications, extensive surgery, etc.
Antithrombin is also used in patients with congenital antithrombin deficiency for the prophylaxis of deep vein thrombosis and thromboembolism in clinical risk situations (especially during surgery or during the peri-partum period) and for the prevention of progression of deep vein thrombosis and thromboembolism in association with heparin, when indicated.
PCC is a complex of human plasma coagulation factors for treatment of bleeding and perioperative prophylaxis of bleeding in acquired prothrombin deficiency, when rapid correction of the deficiency is required.
PCC is also used for treatment of bleeding and perioperative prophylaxis in congenital deficiency of any of the vitamin K dependent coagulation factors when purified specific coagulation factor product is not available.
Rita Garcia-Martinez. Albumin: Pathophysiologic Basis of Its Role in the Treatment of Cirrhosis and Its Complications. Hepatology, Month 2013
Afshari A. Antithrombin III for critically ill patients (Review). The Cochrane Library 2009, Issue 2
Sibylle A. Management of severe perioperative bleeding. Eur J Anaesthesiol 2013; 30:270–382
Rabies is a prolifically deadly zoonotic disease. Rabies-related human deaths are infrequent due to prophylaxis using vaccines and human rabies immunoglobulin (HRIG), providing nearly 100% success rates. Fatalities from rabies occurs when patients fail to seek medical attention. While this does not occur often, preventable deaths were reported within the last year.
Given the rarity of this disease and, therefore, the low incidence of cases reported in medical clinics, hospitals and pharmacies, it is essential for healthcare professionals to have a correct knowledge of the pathology – to immediately recognize its symptoms – and the measures to be taken to procure and administer Human Rabies Immunoglobulins based prophylaxis in combination with the rabies vaccine.
The burden of rabies. Last reviewed September 25, 2017. Accessed March 4, 2019. https://www.cdc.gov/features/dsrabies/index.html
In the last century, transfusion medicine had become a semi-clinical discipline. Unlike other pre- and para-clinical specialties, it dealt not only with patient’s samples but also with blood donors. For the blood donor, blood bankers carry out simple procedures like screening and whole blood collection to complex procedures like apheresis, stem cell harvesting, cord blood banking and plasma and platelets pathogen inactivation. Many centers are even taking up complex procedures like therapeutic apheresis and exchange procedures in patients as bedside procedures.
Plasma S/D (Solvent/Detergent) is fresh frozen plasma (FFP) with a high degree of security because it has undergone treatment with solvent/detergent in order to destroy or inactivate many viruses. It is used in critical care for the same indications of FFP:
- Combined deficiency of coagulation factors such as consumption coagulopathies (Disseminated Intravascular Coagulation – DIC) or Coagulopathy due to severe liver failure or massive transfusion.
- Replacement therapy in deficiency of coagulation factors, in emergency situations when the concentrate is not available to a specific coagulation factor, such as the Factor V or Factor XI, or when it is not possible to determine specific factor deficiency.
- Resolution of fibrinolytic activity and rapid resolution of the effect of oral anticoagulants when the action of vitamin K is insufficient for hepatic impairment or in emergency situations.
Debora Lepri. Utilizzo clinico di plasma virus-inattivato. Recenti Progressi in Medicina, 104 2 (1), Marzo 2013
Safe blood is critical to improving patient outcomes. But the continued risk of transfusion-transmitted infections (TTI) from bacteria and emerging pathogens, as well as blood shortages, have brought global attention to the importance of blood safety and availability.
To mitigate the risk of transfusion transmitted infections and to provide more safety for the patients, pathogen inactivation technology was developed.
The INTERCEPT Blood System is a technology for the broad inactivation of viruses, bacteria, protozoa and white blood cells in plasma and platelets for transfusion. The INTERCEPT Blood System effectively inactivates pathogens and white blood cells using a photosensitizer and UVA light to inhibit the replication and transcription of pathogen genomes in a targeted and specific manner while preserving the blood components’ clinical efficacy. It has a broad inactivation capacity combined with a high efficiency. Multiple studies confirmed that the technology is non-toxic for the transfusion recipient with a very high safety margin.
A large number of clinical trials gave evidence that platelets and plasma treated with the INTERCEPT Blood System are safe and efficacious in comparison to untreated blood components.
It was shown that long-term usage of the INTERCEPT Blood System significantly reduces the incidence of both septic transfusion reactions and the transmission of transfusion-transmitted pathogens. Due to its capacity to inactivate white blood cells, the technology is also approved for both replacement of gamma irradiation and replacement of CMV testing, to prevent GvHD and CMV infection. Inactivation of white blood cells also contributes to the observed reduction of non-hemolytic transfusion reactions.
In summary, the INTERCEPT Blood System is an efficient method to provide additional safety to platelet and plasma transfusion recipients. It minimizes the growing risk of transfusion transmitted infections and their potentially fatal consequences. Additionally, for immune-compromised recipients, it minimizes the risks of TA-GvHD and contributes to the reduction of non-hemolytic transfusion reactions.
Benjamin et al., 2017. Hemovigilance monitoring of platelet septic reactions with effective bacterial protection systems. Transfusion 57: 2946-2957
Cazenave et al., 2011. Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period. Transfusion 51: 622-629
Ciaravino, 2001. Preclinical Safety of a Nucleic Acid-Targeted Helinx Compound: A Clinical Perspective. Semin Hematol 38:12-19
Ciaravino et al., 2003. Preclinical safety profile of plasma prepared using the INTERCEPT Blood Sys. Vox Sang 85:171-182
Cid et al., 2012. Therapeutic efficacy of platelet components treated with amotosalen and ultraviolet A pathogen inactivation method: results of a meta-analysis of randomized controlled trials. Vox Sang 103: 322-330 Cid, 2017
Prevention of transfusion-associated graft-versus-host disease with pathogen-reduced platelets with amotosalen and ultraviolet A light: a review. Vox Sang 112: 607-613
Jimenez-Marco et al., 2012. Pathogen inactivation technology applied to a blood component collected from an asymptomatic carrier of Leishmania infantum: a case report. Vox Sang 103: 356-358
Prowse et al., 2013. Component pathogen inactivation: a critical review. Vox Sang 104: 183-199
Rasongles et al., 2009. Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Réunion. Transfusion 49: 1089-1093 Schlenke, 2014. Pathogen inactivation technologies for cellular blood components: an update. Transfus Med Hemother 41: 309-325
Swissmedic Annual Report 2012-2016. www.swissmedic.ch
Tice et al., 2007. The pathogen reduction treatment of platelets with S-59 HCl (Amotosalen) plus ultraviolet A light: Genotoxicity profile and hazard assessment. Mut Res 630: 50-68
Permira Funds and the Marcucci family complete investment in Kedrion & BPL
- Kedrion Biopharma (“Kedrion”) and Bio Products Laboratory (“BPL”) are two leading bio pharmaceutical companies that develop, manufacture and commercialize therapeutic products from blood plasma
- The Permira Funds have partnered with the Marcucci family to combine two highly complementary companies, BPL and Kedrion, creating an industry leader in plasma derivatives and rare disease medicines
- Ugo Di Francesco, currently CEO of Chiesi Group, has been appointed the new CEO of the combined company, effective January 2023
- Co-founder Paolo Marcucci will remain as Chairman after the arrival of the new CEO
- The combined company, which generates over €1.1B in global revenue, 87% of which comes from outside its Italian and UK home markets, will be headquartered in Italy
01 September 2022 – Permira, the global private equity firm, today announced that funds advised by Permira, in partnership with the Marcucci family and supported by their co-investors, a wholly-owned subsidiary of the Abu Dhabi Investment Authority (ADIA) and Ampersand Capital Partners, have completed the joint acquisition and combination of Kedrion and BPL, alongside Kedrion’s existing shareholders, including FSI and CDP Equity and other minority investors.
The combination of BPL and Kedrion creates a global player for medicinal products derived from human blood plasma, which treat patients with rare and life-threatening conditions. Ugo Di Francesco, currently CEO of Chiesi Group, has been appointed the new CEO of the combined company, effective January 2023. Paolo Marcucci, co-founder of Kedrion, will continue as the combined company’s Chairman and CEO until Ugo Di Francesco joins the business, and thereafter as non-executive Chairman.
Kedrion, headquartered in Tuscany, Italy, has deep Italian heritage and brings an extensive portfolio of 21 products and over 600 marketing authorizations around the world. Kedrion was established by the Marcucci family in 2001 but has roots in the Italian pharmaceutical industry dating back to the 1950s. BPL, headquartered in Elstree, UK, operates a targeted portfolio of successful rare disease products and is one of the fastest growing players in the plasma industry over the past five years. BPL in its present form was created in 2010 but its heritage dates back nearly 70 years as one of the early pioneers of the plasma industry.
The business will have a combined US plasma collection footprint of close to 75 centres, with a portfolio of 37 life-saving products reaching over 100 countries. The business is expected to generate 60% of revenue in the US market with 10 marketed products, building on its strong established positions in Italy and the UK. The company is also establishing a presence in the Chinese market through its recent distribution agreement for Albuminex.
Ugo Di Francesco has been appointed the new CEO of the combined company, effective January 2023. Mr Di Francesco has been CEO of Chiesi Group, a global pharmaceutical company, for over a decade. During this time, he has overseen a period of significant growth for the company, with sales more than doubling from €1.2bn to over €2.5bn and the number of employees from approximately 3,500 to over 6,500. The group has also expanded into new markets under his leadership, in particular in the US and China. Ugo has over 30 years’ experience in the pharmaceutical industry, having previously worked at several leading players, including Sigma-Tau, Amgen Corp., Novartis and Bristol Myers Squibb.
The Permira funds, in partnership with the Marcucci family, will support the combined company to grow organically through the internationalisation of its existing portfolio and the acceleration of new product development, as well as pursuing inorganic growth opportunities to become a further diversified and specialist rare disease platform. FSI and CDP Equity will reinvest alongside Permira and the Marcucci family and support the next phase of development of the business.
Silvia Oteri, Partner and Global Head of Healthcare at Permira, said: “We’re delighted to complete this transaction and now look forward to partnering with the Marcucci family, Ugo and the management teams of Kedrion and BPL to continue developing a combined business serving a global market. Ugo is an outstanding leader with a proven track record of growing global pharmaceutical businesses. With him at the helm, we are excited for this next phase of building a leading rare disease specialist platform that will deliver critical solutions to those in need around the world and with a deep commitment to its donors.”
Paolo Marcucci, Chairman and Chief Executive Officer of Kedrion, added: “This partnership with Permira has made it possible to make an exciting step forward in the history of Kedrion, allowing us to create a global player in the plasma derivatives sector that can successfully compete in a growing market that is increasingly critical in global healthcare. We are proud and grateful for Permira’s support to integrate with BPL and thus significantly increase the global reach and competitiveness of the combined company. Permira’s knowledge of the space is clear and we look forward to leveraging their expertise in value creation to drive growth. To help achieve our goals and ambitions, I am very pleased that Ugo Di Francesco will be on our side as CEO from January next year. His experience and deep knowledge of the pharma sector, together with his leadership qualities and personal attitude, make him the perfect fit for the combined company to meet future challenges and lead the next stages of growth.”
Ugo Di Francesco, incoming CEO of Kedrion, commented: “I am excited to partner with Permira on this exciting project to bring together two high-quality players in the industry and create a truly global leader. Together, Kedrion and BPL will be able to deliver best-in-class patient care and responsible donor engagement and I look forward to driving the growth of the business from next year. I’d like to thank Paolo, the Marcucci family and Permira for their trust and I know that I can rely on the support of the combined team as we continue to serve patients in need around the world.”
The Permira Funds were advised by Morgan Stanley, EY, Latham & Watkins, Alvarez & Marsal, Giliberti, Triscornia e Associati and Maisto e Associati. Kedrion shareholders were advised by Lazard, Natixis, Carnelutti and Pedersoli, whilst the Marcucci family was advised by Terzi&Partners and Carnelutti. BofA Securities and Goodwin Procter served as advisors to BPL and BPL’s sole shareholder, TII.
Permira is a global investment firm that backs successful businesses with growth ambitions. Founded in 1985, the firm advises funds with total assets under management of €60bn+ and makes long-term majority and minority investments across two core asset classes, private equity and credit. The Permira private equity funds have made approximately 300 private equity investments in four key sectors: Technology, Consumer, Healthcare and Services.
The Permira funds have previously invested €4.2bn across 18 investments in healthcare, scaling some of the most innovative healthcare businesses globally across specialty pharma, medical devices, strategic outsourcing platforms and healthcare technology. Previous investments in the sector include Neuraxpharm, Quotient Sciences and LSNE.
Kedrion is a biopharmaceutical company that specializes in the development, production and distribution of plasma-derived therapeutic products for use in treating serious diseases, disorders and conditions such as immune system deficiencies and coagulation disorders. The company operates through a fully integrated business model from the collection of plasma in its own centres in the United States to fractionation and production in its manufacturing facilities located in Italy, Hungary and North America. Headquartered in Castelvecchio Pascoli (Lucca, Italy), Kedrion has approximately 2,800 employees and a commercial presence in 100 countries worldwide. For more information, visit www.kedrion.com
About Bio Products Laboratory (BPL)
Recognising the importance of plasma and with many years of experience in the industry, BPL supplies high-quality plasma derived products to meet the needs of clinicians, patients, and customers globally. Headquartered in the United Kingdom, with US affiliates in Durham, NC and Austin, TX, as well as plasma collection centres across the United States, we are dedicated to producing medicines for the treatment of immune deficiencies, bleeding disorders and infectious diseases as well for critical care. BPL invests in the latest R&D, technology and manufacturing methods, and continuously adapts to ensure that we continue to serve all our stakeholders effectively. For more information visit http://www.bplgroup.com or https://www.bpl-us.com.
BPL consists of two operating divisions — BPL Plasma and BPL Therapeutics. BPL Plasma, operating in the USA, collects plasma from donors in around 29 centres across the U.S. BPL Plasma employs over 900 staff to support the needs of donors and to ensure high-quality plasma collection in all their centres. Plasma collection is regulated by both FDA and MHRA, and BPL Plasma follows industry guidelines. BPL Plasma operates plasma facilities, staffed with trained personnel, dedicated to supporting donors through the process that leads to the donation of plasma. Plasma is shipped to BPL Therapeutics in Elstree, United Kingdom. The plasma is fractionated, purified, and filled through the efforts of our over 1,000 employees involved in production, quality, R&D, commercial, customer services, and administrative activities. BPL’s plasma-derived products are commercially available in the U.K., USA, and 30 plus other countries around the world through our network of local affiliates and distribution partners.
Kedrion grows in North America as it completes acquisition of Prometic
Kedrion has announced that it has completed the acquisition in North America of the Prometic life sciences business.
Prometic, which has a team of 130 employees in Laval, Québec, has developed the first ever FDA-approved treatment for Congenital Plasminogen Deficiency. The new drug, called Ryplazim®,, has been approved for the treatment of all the clinical manifestations of Plasminogen Deficiency, which can lead to blindness, respiratory failure and other severe complications.
Kedrion is now working toward a launch in the United States in early 2022.
“We are very pleased to have completed this important and strategic acquisition, which will bring badly needed therapies to patients who suffer from this rare disease,” said Kedrion’s Chairman Paolo Marcucci,.
The Prometic transaction, Mr. Marcucci added, “is part of our strategy to deepen our commitment and expand our presence across North America, from which we already derive nearly half of our group revenues.”
With the acquisition of Prometic Biotherapeutics Inc., Kedrion has finalized a series of transactions that began last June with the announcement that it was acquiring from Liminal Biosciences Inc. the plasma purification plant at Laval in Québec, and the license to distribute the new product in the United States.
“The Prometic deal brings more cutting-edge purification technology to our group,” said Mr. Marcucci. “But most of all it allows us to reach long-suffering patients who until today have had no effective treatment for the often debilitating condition of Congenital Plasminogen Deficiency.”
Val Romberg, Kedrion’s CEO, also said the most important aspect of the Prometic acquisition was the ability to reach patients in need, “Ryplazim is very significant because it really allows us to fulfil our mission of putting patients first. This is the first drug to ever be approved by the FDA for the treatment of the rare Congenital Plasminogen Deficiency, Type 1, so we are very honored to help speed the product to market.”
Mr. Romberg noted that along with the Laval plant in Québec, Kedrion had also acquired two plasma collection centers in Amherst, New York and in Winnipeg, Manitoba. “We are excited to have new colleagues joining the Kedrion family, and we look forward to working together to get this new treatment to patients as soon as possible,” he said.
Kedrion stronger in North America and further committed to rare diseases
Kedrion Biopharma is expanding its activities in North America and intensifying its commitment in the field of rare diseases thanks to an agreement signed on June 22nd with Liminal BioSciences Inc. (“Liminal BioSciences”), a Canadian company specializing in clinical research and listed on the Nasdaq Global Market (‘LMNL’).
With this agreement Kedrion acquires from Liminal BioSciences a plasma purification business in Laval (Québec, Canada) and the product that will be produced in this plant, which is the first US FDA (Food and Drug Administration) approved drug for the treatment of Congenital Plasminogen (PLG) Deficiency type 1, an ultra-rare systemic disease.
The closing of the transaction is in two phases: Kedrion Biopharma will finalize the acquisition from Liminal BioSciences of its subsidiary Prometic Bioproduction Inc. and consequently will have ownership of the manufacturing operations in Laval. The production facility of Laval has a work force of 135 employees.
The timing for the closing of the remaining part of the agreement (i.e. the acquisition by Kedrion of Liminal’s subsidiary Prometic Biotherapeutics Inc. (PBT), owner of the rights to the product) is linked to the completion of certain conditions by PBT.
On May 21st last, still as part of the overall transaction, Kedrion also acquired from Liminal BioSciences two plasma collection centers, one located in Amherst (New York, USA) and the other in Winnipeg (Manitoba, Canada).
“This transaction – explained Paolo Marcucci, Chairman of Kedrion – represents an opportunity for the future growth of our company: in fact it gives us immediate access to more plasma, it allows us to expand our global operations to Canada and, above all, to enrich our product portfolio with high-impact treatment for patients. For Kedrion it is a further example of our commitment in the fight against rare or ultra-rare diseases and dedication to orphan drugs.”
“This agreement represents an important step toward strengthening the Company’s position in North America – stated Val Romberg, CEO of Kedrion – and in particular toward further growth in the US, which will be the main primary end-market for the product as soon as we are able to start commercialization. We are eager to make this drug available to patients who need it: this represents a further and progressive development in the field of rare and ultra-rare diseases destined to enhance Kedrion’s role as a company dedicated to the needs of patients.”
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