Like troops at the forefront of any battle, our immune system continually marches to protect us from foreign elements and invaders, including bacteria, viruses, and others. Whenever with a swift wave of wind, something falls in our eyes, our immune system produces tears to get rid of the invader. Or at times when we scrape our bodies and start to bleed, how the blood itself starts to clot, and within days to weeks, the wound vanishes. However, this process is not as simple as it may look appear. Blood clotting is one of the most complex innate processes that employ numerous types of cells from varied locations. During the whole process, Fibrinogen, the most abundant protein of the blood plasma after albumin and immunoglobulins, gets converted into insoluble protein fibrin. It is specifically a clotting factor (factor I). It is one of the 13 coagulation factors responsible for normal blood clotting.
However, abnormally low levels of fibrinogen can lead to Fibrinogen disorders. When the fibrinogen levels range between 0.2 and 0.8 g/L, it is referred to a rare condition called Hypofibrinogenemia. It is a quantitative defect in fibrinogen, which results from mutations that affect plasma fibrinogen concentration inherited on both chromosomal alleles. Also, it is frequently associated with a bleeding diathesis and occasionally a thrombotic event. Hypofibrinogenemia can either be congenital or acquired.
According to a North American Registry of Rare Bleeding Disorders, Hypofibrinogenemia accounted for about 38% of the total fibrinogen disorders cases. Although the exact Hypofibrinogenemia prevalence is unknown, however, International blood registries suggest that congenital fibrinogen deficiency is one of the rarest of rare bleeding disorders. DelveInsight estimates that Acquired Hypofibrinogenemia is more frequent as compared to congenital. Approximately 65–70% of the people get the Acquired form of the disorder. People get Acute acquired hypofibrinogenemia due to cardiac surgery, liver surgery, postpartum hemorrhage, trauma, and non-surgical/non-traumatic bleeding.
Since the disorder causes non-stop bleeding, the aim of the treatment is to either prevent or control bleeding by increasing the levels of fibrinogen, known as factor replacement treatment. It is achieved with the help of fibrinogen concentrates, which are, at the moment, the mainstay of Hypofibrinogenemia treatment. It is recommended for congenital Hypofibrinogenemia in the US and Europe both, while for acquired Hypofibrinogenemia, only in Europe. RiaSTAP, a purified fibrinogen concentrate of CSL Behring, became the first drug to get approval from the FDA for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and congenital hypofibrinogenemia and is the most widely used therapy.
In the absence of fibrinogen concentrates, fresh frozen plasma (FFP) is used. It contains fibrinogen is comparatively a cheaper alternative; however, requires the administration of large quantities of fluid to achieve a reasonable fibrinogen dose. Cryoprecipitate is another substitute that is used. A general transfusion threshold of 1 g/dL can also be seen prescribed to treat hypofibrinogenemia in the context of a bleeding patient.
However, none of the available options are curative in nature, and the data for the safety and efficacy of the available options are limited. Rare bleeding disorders are prevalent worldwide; even so, the understanding of such disorders remains scarce. Management and treatment of Hypofibrinogenemia are suboptimal, and patients often experience morbidity and mortality. The rarity of the disease renders health care professionals with little or no experience and knowledge of diagnosis and prognosis, which further worsens the situation.
The Hypofibrinogenemia market requires curative treatment options, new diagnostics methodologies for easier identification of high-risk patients, and safer, standard, and effective replacement therapy. There is only a limited number of pharma companies that are working to develop therapies in the Hypofibrinogenemia market. Among the emerging drugs, the candidate of Biotest A is the only one in the late-stage development for the management of fibrinogen deficiency, including hypofibrinogenemia. BT-524 is a human fibrinogen concentrate, which is administered intravenously. Recently, the company announced the completion of the phase I/III clinical trial with fibrinogen in a watershed movement. The prospective, open, multicentre phase I/III study investigated the pharmacokinetic properties, efficacy, and safety of fibrinogen concentrate in adults and children with congenital fibrinogen deficiency. Additionally, the therapy is also tested in cases of acquired fibrinogen deficiency. Being the only play investigating therapies for rare bleeding disorders at late-stages gives the company an upper hand.
However, there remains a lot to achieve. Collectively, rare bleeding disorders are prevalent worldwide, and lack of knowledge delays diagnosis. Only a few therapies have been approved so far, and the Hypofibrinogenemia pipeline looks bleaker, with only a handful of companies operating in the domain. Nevertheless, just like every coin has two faces, the Hypofibrinogenemia market can also be seen as an opportunity for the pharmaceutical players to flourish and reap benefits in the rare disease market.