Hemophilia is a rare genetic disorder that tends to failure in the blood coagulation pathway. Hemophilia occurs when the body is not making enough proteins (clotting factors) that help in blood coagulation. Clotting factors are the blood coagulation proteins that aid platelets to make clot1.
There are several types of hemophilia. It may be severe, moderate, or mild based on the number of clotting factors in your body.
- Hemophilia A: it occurs due to a lack of clotting factor VIII and has a higher prevalence rate of 10 in 100,000, according to the CDC.
- Hemophilia B: it occurs due to a lack of clotting factor IX and has a lower prevalence rate of 1 in 100,1000, according to CDC.2
Treatment options for hemophilia:
Hemophilia is usually treated by administrating clotting concentrates into the patient’s vein, called the clotting factor replacement therapy. Clotting concentrates include plasma-derived factor concentrates, and recombinant factor concentrates. These are obtained from human plasma and genetic engineering using DNA technology, respectively. Other treatment options include Desmopressin Acetate, Epsilon Amino Caproic Acid, and Cryoprecipitates.3
Regrettably, the previous treatment option did not yield a satisfactory outcome. The unwelcome clotting factors are usually destroyed by the body’s in-Bliton immune response(antibodies). These antibodies are called inhibitors. This results in an overall decrease in the efficacy of the replacement therapy regimen.
As an alternative, factor VIII mimetic monoclonal antibody, Emicizumab has been used as a non-clotting factor alternative therapy.4 It is administered through subcutaneous injections and was approved by the FDA in 2018 for patients with and without inhibitors. Emicizumab is recommended by the World Federation for the prophylaxis of hemophilia A over bypassing agents. Previously, there was no treatment option available for hemophilia B that could surpass the bypassing agents, such as Emicizumab.
Role of concizumab :
Concizumab, a monoclonal antibody, has shown very promising results in hemophilic patients with inhibitors. It is an anti-tissue factor pathway inhibitor (TFPI) antibody that is also administered subcutaneously for all hemophilia types. It potentially represents the first subcutaneous treatment option for hemophilia B with inhibitors.
In phase 3 of the Explorer 7 trial, 133 patients were involved, all with inhibitors. 80 patients were hemophilic A and 53 were hemophilic B. All the patients who were on treatment of by-passing agents were divided into 4 groups or arms. Arm 1 was randomly assigned to receive no prophylaxis for at least 24 weeks (n=19). Arm 2 is assigned to receive concizumab prophylaxis for at least 32 weeks (n=33), while arms 3 and 4 are non-randomly assigned to receive concizumab for at least 24 weeks (n=81).
The primary endpoint of the study showed a significantly lower mean annualized bleeding rate of 1.7 in the concizumab prophylaxis 32-week group vs 11.8 in non-prophylactic patients (rate ratio, 0.14; P < .001). Fortunately, there were no significant side effects noted in concizumab prophylaxis5. Initially, the FDA rejected the application of drug approval, requesting more evidence for the drug manufacturing and dosage plan prior to its administration in patients. Meanwhile, Canada recently approved concizumab in March 2023 for the treatment of hemophilia B with inhibitors in adolescent and adult patients.6
REFERENCES:
- Quick AJ. Symposium: What Is Hemophilia?: On the Nature and Diagnosis of Hemophilia. Blood. 1954 Mar 1;9(3):265-72.
- https://my.clevelandclinic.org/health/diseases/14083-hemophilia#:~:text=Hemophilia%20A%3A%20This%20is%20the,factor%209%20(factor%20IX.)
- https://www.cdc.gov/ncbddd/hemophilia/treatment.html
- Blair HA. Emicizumab: a review in hemophilia A. Drugs. 2019 Oct;79(15):1697-707
- Matsushita T, Shapiro A, Abraham A, Angchaisuksiri P, Castaman G, Cepo K, d’Oiron R, Frei-Jones M, Goh AS, Haaning J, Hald Jacobsen S. Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. New England Journal of Medicine. 2023 Aug 31;389(9):783-94.
- https://www.mdedge.com/hematology-oncology/article/265057/bleeding-disorders/hemophilia-concizumab-lessens-bleeding-could