Rare Disease Day 2023: spotlight on congenital fibrinogen deficiency

Globally coordinated by The European Organization for Rare Diseases (EURORDIS), and over 65 national alliance patient organisation partners, Rare Disease Day aims to increase awareness and promote necessary changes for the 300 million people worldwide living with a rare disease. Over 600 events will be taking place this year in more than 100 countries across the globe, including social media campaigns, school events, conferences, and political advocacy campaigns, continuing to strengthen the diverse international rare disease community.

Rare Disease Day also gives the world an opportunity to cast a spotlight on rare and frequently overlooked conditions such as congenital fibrinogen deficiency (CFD). CFD is an extremely rare, genetically inherited blood disorder affecting fibrinogen (factor I), where the blood does not clot normally. CFD results in abnormal forms or low levels of fibrinogen, which is a protein that accounts for 95% of all coagulation factors in the bloodstream and is the major structural component of a blood clot. Therefore, patients with CFD have trouble maintaining haemostasis and experience bleeding episodes.

Despite incentives offered by processes such as orphan drug designation, unmet needs remain persistent across many rare diseases due to their small global patient populations and limited commercial opportunities. CFD is an extremely rare disease, in which many patients are often asymptomatic and do not require treatment. Since the drug-treated CFD population is very small, drug developers are not heavily invested in the space and clinical trials frequently struggle with recruitment, especially in areas with low diagnosed prevalence.

An urgent unmet need exists among the CFD population for new and differentiated treatment options. Current treatment options for CFD are limited to the use of four human fibrinogen concentrate (HFC) products, which serve as intravenous (IV) replacement therapy for fibrinogen (factor I) to control and prevent bleeding episodes in symptomatic patients. Two HFCs are marketed in the US (RiaSTAP and Fibryga), while three products are available in Germany (RiaSTAP/Haemocomplettan P, Fibryga, and FibCLOT), with only one marketed product available for use in Japan (Fibrinogen HT).

HFC products are derived from human plasma and carry risks of infection and blood clots. They also must be administered intravenously in a healthcare setting, which is extremely inconvenient for patients and caregivers. Further, because there are only four available HFC products worldwide, many countries and patients are left without access to treatment.

Currently, only two pipeline HFCs are in late-stage development: Biotest/Grifols‘s BT-524, and Grifols’s FIB Grifols. Both products use Biotest’s newly developed production facility, which enables the improved manufacturing of fibrinogen with a higher purity, defined concentrations, and guaranteed viral safety. While these agents are new and improved, they still belong to the same therapeutic class as all four current treatment options. Therefore, the unmet need for innovative and differentiated therapies remains unaddressed.

Lastly, replacement therapy with HFC can treat the symptoms of CFD, but does not provide a permanent cure. There is also a significant need for new therapies that target the underlying genetic cause of CFD, which may offer a cure for patients living with severe disease, or for patients with genotypes such as dysfibrinogenemia and hypodysfibrinogenemia, who are often ineligible for treatment with HFCs. While CFD patients do have some treatment options, increased awareness and research within the field may offer an improved quality of life for this vulnerable population.