RARE DISEASE
Severe hemophilia B
Severe hemophilia B
Severe hemophilia B
Synonyms: Severe congenital F9 deficiency, Severe congenital factor IX deficiency
Synonyms: Severe congenital F9 deficiency, Severe congenital factor IX deficiency
Synonyms: Severe congenital F9 deficiency, Severe congenital factor IX deficiency
Drug discovery
0
drugs
With orphan designations
Overview
Severe Hemophilia B is an X-linked bleeding disorder caused by mutations in the F9 gene, resulting in factor IX (FIX) activity <1%. Patients experience spontaneous bleeding into joints/muscles, leading to chronic arthropathy and disability. Management involves FIX replacement, prophylaxis, and emerging therapies like gene therapy (e.g., Hemgenix®). Early diagnosis via clotting assays and treatment at specialized hemophilia centers are critical to reducing morbidity [1][6][16].
Burden
Economic: Annual healthcare costs exceed $630,000 for severe cases, driven by factor replacement [4][9][19].
Morbidity: Chronic pain (40–70% of adults), arthropathy, and reduced quality of life (EQ-5D-5L utility: 0.76) [5][14][20].
Mortality: Historical risks from HIV/hepatitis C; modern care near-normalizes life expectancy [2][8][20].
Categories: rare genetic diseases, rare hematological diseases
Research Papers
931 drug discovery papers about Severe hemophilia B, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
931 drug discovery papers about Severe hemophilia B, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-01 | Bridging The Gap Between Traditional Factor Replacement Therapy and Novel Non-Factor Replacement Therapy in Hemophilia
Hemophilia, which means “love” (philia) of blood (hem), is the most common severe hereditary hemorrhagic disease. Hemophilia A and B are congenital bleeding disorders caused by an absence or complete lack of coagulation factor VIII (FVIII) or factor IX (FIX), respectively.[1] It can be recognized by the prolonged and heavy bleeding that occurs after minor trauma and occasionally on its own. Hemophilia is more common in men than in women (1 in 10,000 for men and 1 in 100,000,000 for women) [3]. Hemophilia was once called as “the royal disease” [4]. Arthropathy is a frequent result of hemophilia, mainly arising from ongoing bleeding in the elbows, knees, and ankles caused by the lack of coagulation factors [6].When a joint experiences repeated episode of bleeding (known as a target joint), it undergoes chronic alterations [7]. The 1964 finding by Judith Pool that the cryoprecipitate obtained from plasma had high concentrations of FVIII marked a significant advancement in the treatment of hemophilia[4]. The most significant and challenging problem with managing hemophilia is the development of inhibitors, which makes it hard to implement safe and efficient standards of care, especially in prophylaxis [2]. innovative methods of action that aimed to imitate coagulation factor VIII or restore thrombin production. New non-replacement therapies are being tested in clinical trials to reduce the treatment burden for patients with hemophilia A or B, regardless of the presence of inhibitors, in addition to the bispecific monoclonal antibody emicizumab, which is already approved for patients with severe hemophilia A both with and without inhibitors. These treatments have the potential to provide effective bleeding prevention, improve patient adherence, and improve the general health-related quality of life for hemophiliacs due to their distinct mechanisms and subcutaneous delivery [46].
2026-08-01 | Subcutaneous MG1113 in severe hemophilia A&B: Phase 1b study for safety, pharmacokinetics, and pharmacodynamics
Background MG1113 is an IgG4 monoclonal antibody targeting the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), developed as a hemostatic rebalancing agent for hemophilia A or B. Objectives We aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary hemostatic effects of MG1113. Methods This phase 1b clinical trial was constructed in a multicenter, prospective, stepwise dose-escalating (2.0, 3.0, and 3.3 mg/kg) design. MG1113 was administered subcutaneously once weekly for 8 weeks. Results Fifteen male patients (n=5/cohort) diagnosed with severe hemophilia A (n=14) or B (n=1) without inhibitors were enrolled. MG1113 was well tolerated, with an adverse event rate of 40.0% (6/15). No serious adverse events, early withdrawals, or dose interruptions occurred. PK analysis demonstrated a non-linear profile, with the peak plasma concentration at 33-48 hours post-dose. Free TFPI and diluted prothrombin time decreased from baseline, while thrombin generation markers increased. Exploratory analysis showed a notable numerical reduction in annualized total bleeding rates at higher doses: 91.7% at 3.0 mg/kg and 76.2% at 3.3 mg/kg. Zero bleeding rate was 20.0%, 60.0%, and 40.0% at doses of 2.0, 3.0, and 3.3 mg/kg, respectively. Conclusion MG1113, administered subcutaneously as a prophylaxis in severe hemophilia A or B without inhibitors for 8 weeks, demonstrated an acceptable safety profile with a PK profile suitable for once-a-week dosing. The PD marker changes were consistent with TFPI inhibition, which was associated with reductions in bleeding events.
2026-07-30 | Concizumab prophylaxis in a 2-year-old patient with severe hemophilia B and inhibitor: a case report.
Hemophilia B is a rare X-linked congenital bleeding disorder characterized by a deficiency in coagulation factor IX (FIX). Standard management relies on exogenous factor replacement; however, the development of neutralizing alloantibodies (inhibitors) against infused clotting factor can significantly reduce therapeutic efficacy and complicate long-term management. Consequently, patients turn to bypassing agents or non-factor therapies to help achieve adequate hemostatic control. Concizumab is a novel subcutaneous non-factor therapy for hemophilia A and B that targets the tissue factor pathway inhibitor (TFPI). While it is approved for patients >12 years old, data remains sparse in younger children. Prophylactic treatment with concizumab reduces several limitations associated with inhibitor development and variability in treatment response with conventional therapies, especially in pediatric populations. We report a toddler with hemophilia B who developed a low-titer inhibitor following treatment with recombinant coagulation factor IX agents, resulting in recurrent bleeding complications and consistent subtherapeutic hemostatic control on standard bypassing agents. The patient was transitioned to concizumab for long-term prophylaxis, with dose adjustments based on clinical response and concizumab drug levels. Following the initiation of concizumab, the patient demonstrated a marked reduction in bleeding episodes. We highlight an individualized early drug-level-guided dose escalation approach in a very young child, demonstrating that pharmacokinetic monitoring can be utilized proactively to optimize therapeutic response in this age group, leading to effective drug levels and excellent clinical response. This case supports the role of concizumab in potentially reducing treatment burden and improving hemostatic outcomes in young patients with severe hemophilia B and inhibitors.
2026-07-23 | Haemodialysis in haemophilia B: a case report. Challenges and strategies from a nephrology perspective.
Haemophilia B, the result of factor IX deficiency, is a complex clinical condition that is particularly challenging when associated with kidney failure. This is primarily due to the high bleeding risk associated with kidney replacement therapies. The increase in life expectancy in haemophilia patients has resulted in a greater prevalence of age-related comorbidities, including chronic kidney disease. Nevertheless, a consensus has yet to be reached regarding the most suitable dialysis modality for this population. In this report, we present a case study of a 68-year-old male patient suffering from severe haemophilia B, who was administered prophylactic Idelvion® (albutrepenonacog alfa) and subsequently underwent arteriovenous fistula creation and haemodialysis initiation without encountering any bleeding complications. This narrative review, from the perspective of a nephrologist, addresses the epidemiology and main clinical considerations regarding dialysis in haemophilia B. These considerations include the choice between haemodialysis and peritoneal dialysis, vascular access planning, haemostasis management with factor IX replacement, and anticoagulation strategies aimed at minimising bleeding risk. A review of the extant literature and clinical reports published between 2020 and 2025 was conducted, integrating documented experiences and available guideline recommendations. In addition, we put forward a series of pragmatic recommendations that are -underpinned by a systematic decision-making framework. Through meticulous multidisciplinary planning incorporating the utilisation of factor IX concentrates, meticulous surgical techniques, and tailored anticoagulation protocols, patients with haemophilia B can be deemed eligible for chronic haemodialysis with a reasonable degree of safety.
2026-07-14 | CLINICAL AND LABORATORY CHARACTERISTICS, INHIBITOR FORMATION, AND THE EFFICACY OF MONOCLONAL ANTIBODY THERAPY IN CHILDREN WITH HEMOPHILIA A AND B
Hemophilia A (HA) and B (HB) are severe hereditary coagulopathies, the main complication of replacement therapy for which is the formation of inhibitors to coagulation factors. The aim of the study was to conduct a comparative analysis of the clinical and laboratory features of the onset, to evaluate the dynamics of therapy and the frequency of inhibitor formation in children with GA and GV, using monoclonal antibodies – emicizumab (MtAB) in pediatric practice. A retrospective cohort study of 68 patients with congenital coagulopathies (GA – 58, GV – 10) observed in the State Autonomous Healthcare Institution of the Sverdlovsk Region "Regional Clinical Hospital" (Yekaterinburg) by a hematologist in 2015-2025. The onset of inhibitory GA (Me = 4.5 months) was significantly earlier than non-inhibitory (Me = 9 months, p = 0.032), and hemorrhagic syndrome at the debut was more common in GV (100% versus 63.8% in GA, p = 0.029). Ferritin levels in GA were significantly lower (Me=23 μg/L) than in BG (Me=73 μg/L, p=0.003), indicating chronic blood loss. By 2025, inhibitors had developed in 21 patients with GA (36.2%). Switching 12 patients from GA to MtAT resulted in a reduction in the annual bleeding rate (ABR) from 8.5 to 1.0 (p<0.001), and in patients with an inhibitor form, a significant reduction in the inhibitor titer from 3.0 to 0.2 BU (p<0.05). Early onset predicts a high risk of inhibitor formation, and the high cumulative inhibitor rate (36.2%) necessitates regular screening, as MtAT therapy demonstrates high clinical efficacy and a favorable safety profile in children with GA, including patients with inhibitors.
2026-08-01 | Bridging The Gap Between Traditional Factor Replacement Therapy and Novel Non-Factor Replacement Therapy in Hemophilia
Hemophilia, which means “love” (philia) of blood (hem), is the most common severe hereditary hemorrhagic disease. Hemophilia A and B are congenital bleeding disorders caused by an absence or complete lack of coagulation factor VIII (FVIII) or factor IX (FIX), respectively.[1] It can be recognized by the prolonged and heavy bleeding that occurs after minor trauma and occasionally on its own. Hemophilia is more common in men than in women (1 in 10,000 for men and 1 in 100,000,000 for women) [3]. Hemophilia was once called as “the royal disease” [4]. Arthropathy is a frequent result of hemophilia, mainly arising from ongoing bleeding in the elbows, knees, and ankles caused by the lack of coagulation factors [6].When a joint experiences repeated episode of bleeding (known as a target joint), it undergoes chronic alterations [7]. The 1964 finding by Judith Pool that the cryoprecipitate obtained from plasma had high concentrations of FVIII marked a significant advancement in the treatment of hemophilia[4]. The most significant and challenging problem with managing hemophilia is the development of inhibitors, which makes it hard to implement safe and efficient standards of care, especially in prophylaxis [2]. innovative methods of action that aimed to imitate coagulation factor VIII or restore thrombin production. New non-replacement therapies are being tested in clinical trials to reduce the treatment burden for patients with hemophilia A or B, regardless of the presence of inhibitors, in addition to the bispecific monoclonal antibody emicizumab, which is already approved for patients with severe hemophilia A both with and without inhibitors. These treatments have the potential to provide effective bleeding prevention, improve patient adherence, and improve the general health-related quality of life for hemophiliacs due to their distinct mechanisms and subcutaneous delivery [46].
2026-08-01 | Subcutaneous MG1113 in severe hemophilia A&B: Phase 1b study for safety, pharmacokinetics, and pharmacodynamics
Background MG1113 is an IgG4 monoclonal antibody targeting the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), developed as a hemostatic rebalancing agent for hemophilia A or B. Objectives We aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary hemostatic effects of MG1113. Methods This phase 1b clinical trial was constructed in a multicenter, prospective, stepwise dose-escalating (2.0, 3.0, and 3.3 mg/kg) design. MG1113 was administered subcutaneously once weekly for 8 weeks. Results Fifteen male patients (n=5/cohort) diagnosed with severe hemophilia A (n=14) or B (n=1) without inhibitors were enrolled. MG1113 was well tolerated, with an adverse event rate of 40.0% (6/15). No serious adverse events, early withdrawals, or dose interruptions occurred. PK analysis demonstrated a non-linear profile, with the peak plasma concentration at 33-48 hours post-dose. Free TFPI and diluted prothrombin time decreased from baseline, while thrombin generation markers increased. Exploratory analysis showed a notable numerical reduction in annualized total bleeding rates at higher doses: 91.7% at 3.0 mg/kg and 76.2% at 3.3 mg/kg. Zero bleeding rate was 20.0%, 60.0%, and 40.0% at doses of 2.0, 3.0, and 3.3 mg/kg, respectively. Conclusion MG1113, administered subcutaneously as a prophylaxis in severe hemophilia A or B without inhibitors for 8 weeks, demonstrated an acceptable safety profile with a PK profile suitable for once-a-week dosing. The PD marker changes were consistent with TFPI inhibition, which was associated with reductions in bleeding events.
2026-07-30 | Concizumab prophylaxis in a 2-year-old patient with severe hemophilia B and inhibitor: a case report.
Hemophilia B is a rare X-linked congenital bleeding disorder characterized by a deficiency in coagulation factor IX (FIX). Standard management relies on exogenous factor replacement; however, the development of neutralizing alloantibodies (inhibitors) against infused clotting factor can significantly reduce therapeutic efficacy and complicate long-term management. Consequently, patients turn to bypassing agents or non-factor therapies to help achieve adequate hemostatic control. Concizumab is a novel subcutaneous non-factor therapy for hemophilia A and B that targets the tissue factor pathway inhibitor (TFPI). While it is approved for patients >12 years old, data remains sparse in younger children. Prophylactic treatment with concizumab reduces several limitations associated with inhibitor development and variability in treatment response with conventional therapies, especially in pediatric populations. We report a toddler with hemophilia B who developed a low-titer inhibitor following treatment with recombinant coagulation factor IX agents, resulting in recurrent bleeding complications and consistent subtherapeutic hemostatic control on standard bypassing agents. The patient was transitioned to concizumab for long-term prophylaxis, with dose adjustments based on clinical response and concizumab drug levels. Following the initiation of concizumab, the patient demonstrated a marked reduction in bleeding episodes. We highlight an individualized early drug-level-guided dose escalation approach in a very young child, demonstrating that pharmacokinetic monitoring can be utilized proactively to optimize therapeutic response in this age group, leading to effective drug levels and excellent clinical response. This case supports the role of concizumab in potentially reducing treatment burden and improving hemostatic outcomes in young patients with severe hemophilia B and inhibitors.
2026-07-23 | Haemodialysis in haemophilia B: a case report. Challenges and strategies from a nephrology perspective.
Haemophilia B, the result of factor IX deficiency, is a complex clinical condition that is particularly challenging when associated with kidney failure. This is primarily due to the high bleeding risk associated with kidney replacement therapies. The increase in life expectancy in haemophilia patients has resulted in a greater prevalence of age-related comorbidities, including chronic kidney disease. Nevertheless, a consensus has yet to be reached regarding the most suitable dialysis modality for this population. In this report, we present a case study of a 68-year-old male patient suffering from severe haemophilia B, who was administered prophylactic Idelvion® (albutrepenonacog alfa) and subsequently underwent arteriovenous fistula creation and haemodialysis initiation without encountering any bleeding complications. This narrative review, from the perspective of a nephrologist, addresses the epidemiology and main clinical considerations regarding dialysis in haemophilia B. These considerations include the choice between haemodialysis and peritoneal dialysis, vascular access planning, haemostasis management with factor IX replacement, and anticoagulation strategies aimed at minimising bleeding risk. A review of the extant literature and clinical reports published between 2020 and 2025 was conducted, integrating documented experiences and available guideline recommendations. In addition, we put forward a series of pragmatic recommendations that are -underpinned by a systematic decision-making framework. Through meticulous multidisciplinary planning incorporating the utilisation of factor IX concentrates, meticulous surgical techniques, and tailored anticoagulation protocols, patients with haemophilia B can be deemed eligible for chronic haemodialysis with a reasonable degree of safety.
2026-07-14 | CLINICAL AND LABORATORY CHARACTERISTICS, INHIBITOR FORMATION, AND THE EFFICACY OF MONOCLONAL ANTIBODY THERAPY IN CHILDREN WITH HEMOPHILIA A AND B
Hemophilia A (HA) and B (HB) are severe hereditary coagulopathies, the main complication of replacement therapy for which is the formation of inhibitors to coagulation factors. The aim of the study was to conduct a comparative analysis of the clinical and laboratory features of the onset, to evaluate the dynamics of therapy and the frequency of inhibitor formation in children with GA and GV, using monoclonal antibodies – emicizumab (MtAB) in pediatric practice. A retrospective cohort study of 68 patients with congenital coagulopathies (GA – 58, GV – 10) observed in the State Autonomous Healthcare Institution of the Sverdlovsk Region "Regional Clinical Hospital" (Yekaterinburg) by a hematologist in 2015-2025. The onset of inhibitory GA (Me = 4.5 months) was significantly earlier than non-inhibitory (Me = 9 months, p = 0.032), and hemorrhagic syndrome at the debut was more common in GV (100% versus 63.8% in GA, p = 0.029). Ferritin levels in GA were significantly lower (Me=23 μg/L) than in BG (Me=73 μg/L, p=0.003), indicating chronic blood loss. By 2025, inhibitors had developed in 21 patients with GA (36.2%). Switching 12 patients from GA to MtAT resulted in a reduction in the annual bleeding rate (ABR) from 8.5 to 1.0 (p<0.001), and in patients with an inhibitor form, a significant reduction in the inhibitor titer from 3.0 to 0.2 BU (p<0.05). Early onset predicts a high risk of inhibitor formation, and the high cumulative inhibitor rate (36.2%) necessitates regular screening, as MtAT therapy demonstrates high clinical efficacy and a favorable safety profile in children with GA, including patients with inhibitors.
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