See ((Hemophilia B))
Vitamin K dependent protein.
Single chain glycoprotein synthesized by the hepatocyte as a precursor protein, which undergoes extensive posttranslational modification to become gamma-carboxylated mature zymogen secreted into the blood.
Levels in newborns and children are lower than in adults, and increase with age.
Deficiency responsible for hemophilia B.
Hemophila B is a X-linked bleeding disorder caused by partial or complete deficiency of circulating factor IX activity due to mutation in the gene F9.
Deficiency termed Christmas disease and is inherited as an X-linked inherited bleeding disorder.
Manifests in males and transmitted by females that carry the abnormality on the X chromosome.
Affects about one in every 25,000 male births and rarely in females.
Worldwide, approximately 33,000 people have hemophilia B, and 2/3 of these persons have hemophilia classified on the basis of plasma factor IX activity as moderate, activity of 1 to 5% or severe, with activity levels of less than 1%.
Hemophilia B is caused by mutations in the gene encoding coagulation factor IX that leads to decreased production of the protein, and insufficient coagulation factor IX resulting in a bleeding tendency that classically involves musculoskeletal tissues, but can affect other tissues and critical organs.
Associating with recurrent bleeding episodes leading to painful hemarthrosis, disabling arthropathy and other complications.
Severe hemophilia B is characterized by coagulation factor IX levels of less than 1% of the normal value, less than one IU per deciliter.
Prophylactic replacement with factor IX intravenous infusions is associated with improved clinical outcomes.
Factor IX available products require frequent intravenous injections of about two or three times a week to maintain protective level at or above one international unit per deciliter.
Factor IX FC fusion protein, eftrenonacog alfa administered prophylactically can be given every one to weeks and results in low annualized bleeding rates in patients with Hemophilia B (B-LONG investigators).
A recombinant Factor IX protein drug (Alprolix) for hemophilia B administered weekly or even less frequently approved indications include controlling acute bleeding episodes, managing bleeding during surgical procedures, and for bleeding prophylaxis.
After an initial run-in period, the median dosing interval was 14 days for Alprolix.
It consists of the Factor IX protein fused to an Fc globulin fragment, resulting in slowing of the molecule’s degradation in the circulation to prolong its half-life.
A recombinant Factor IX drug, Rixubis, which is administered twice weekly for prophylaxis is also available.
Albutrepenonacog alfa for Hemophilia B is the first long-acting Hemophilia B Drug.
A drug for children and adults with hemophilia B, albutrepenonacog alfa (Idelvion), which combines albumin with factor IX to reduce injection frequency.
Albutrepenonacog alfa is the first recombinant coagulation factor IX product approved by the FDA that contains albumin.
It is the second FDA-approved product that combines the clotting factor with any sort of protein that prolongs circulation time.
The first was eftrenonacog alfa ( Alprolix), which fuses factor IX to the Fc portion of IgG subclass I.
Albutrepenonacog alfa is indicated specifically for on-demand control and prevention of bleeding episodes, management of postoperative bleeding, and as prophylaxis to reduce the frequency of bleeding episodes.
Albutrepenonacog for hemophilia B is safe and effective based on two multicenter studies involving 90 patients aged between 1 and 61 years.
Albutrepenonacog alfa effectively controlled bleeding episodes, including those after surgery.
Etranacogene dezaparvovec approved for use an adult with hemophilia B.
Etranacogene dezaparvovec gene therapy is superior to prophylactic factor IX with respect to annualized bleeding rate and has a favorable safety profile.
Current gene therapy for factor IX hemophilia can increase the level effective of factor IX to greater than 30% with clinical improvement at more than 5% of the normal level.
Used prophylactically, it significantly reduced the rate of spontaneous bleeding episodes per year despite less frequent infusions.
Headache was the only adverse event observed in the studies, which did not identify any safety concerns.
Albutrepenonacog alfa in a phase 3 study spanning more than one year successfully treated 98.6% of bleeding episodes in 63 patients with severe hemophilia B including 93.6% treated with a single injection.
Verbrinacogene setparvovec is a liver directed adeno–associated virus gene therapy that uses a synthetic capsid and gain of function proteins to normalize factor IX levels in patients with hemophilia B: sustained factor nine levels in the normal range were observed with low doses of this drug but necessitated immunosuppression with glucocorticoids with or without tacrlolimus (Chowdary P).
Etranacogene dezaparvovec gene therapy is superior to prophylactic factor IX with respect to annualized bleeding rate and has a favorable safety profile.
Fidanacogene elaparvovec, and adeno- associated virus gene therapy vector for hemophilia B containing a high active human factor IV variant is associated with sustained factor IX activity to reduce bleeding and stable factor IX expression.