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
918 drug discovery papers about Severe hemophilia B, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
918 drug discovery papers about Severe hemophilia B, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-07 | Real-World Outcomes of Prophylaxis With rIX-FP in Germany: A Prospective, Non-Interventional Study in Haemophilia B.
Efficacy and safety of albutrepenonacog alfa (rIX-FP) in people with haemophilia B (PwHB) has been previously demonstrated in clinical trials. However, real-world data insights are required. To describe real-world effectiveness and tolerability of rIX-FP in PwHB in Germany. Prospective, non-interventional study conducted across 19 sites in Germany. Patients of any age treated with rIX-FP were enrolled between March 2018 and February 2024. Patients were monitored every 3-12 months and followed-up for 3 years or until ≥100 exposure days. To our knowledge, this is the largest study of factor replacement therapy in PwHB in Germany to date. Of the patients who completed the study (63/73), most (80.8%) had moderate or severe haemophilia B. The mean (standard deviation) duration of observation was 30.5 (8.32) months. For any prophylaxis regimen, the median (range) annualised bleeding rate (ABR) was 0.89 (0.0-9.6) and annualised spontaneous bleeding rate (AsBR) was 0.08 (0.0-5.2). The median ABR was 1.12, 0.68 and 0.13, and the median AsBR was 0.17, 0.00 and 0.06 for those treated with a 7-, 10- or 14-day regimen, respectively. Investigators rated the overall haemostatic effectiveness as 'good' or 'excellent' in 94% of cases (based on the worst assessment). Overall, 82 adverse events in 34 patients were reported, none were considered related to rIX-FP. This multicentre, non-interventional study in Germany demonstrates that rIX-FP prophylaxis is effective and well tolerated in PwHB of all ages in routine clinical practice and reinforces the results of the clinical trials.
2026-06-30 | Anti-TFPI Single-Domain Antibodies: Novel Rebalancing Therapies for Hemophilia and Other Rare Bleeding Disorders
Tissue factor pathway inhibitor (TFPI) is an important determinant of thrombin generation in patients with deficiency in factor (F)VIII, FIX, and FXI. As such, anti-TFPI monoclonal antibodies such as concizumab have been developed to treat hemophilia A (HA) and B (HB).The objective of this study is to generate single-domain antibodies (sdAbs) as a novel class of pharmacological agents blocking TFPI and increasing thrombin generation in the plasma of patients with severe HA, HB, and FXI deficiency.A large synthetic library of sdAbs was generated and selected by phage-display on recombinant human TFPIα (rhTFPIα). Anti-TFPI sdAbs were screened on their ability to promote thrombin generation. Their binding to the Kunitz (K1, K2, K3) domains of TFPIα were measured by enzyme-linked immunosorbent assay. Their effects on the inhibitory activity of rhTFPIα toward FXa and TF/FVIIa complex were tested in purified systems. Thrombin generation was measured on plasmas from patients with severe HA, HB, or FXI-deficiency spiked with the anti-TFPI sdAbs.A total of 14 out of 188 screened sdAbs specifically bound to rhTFPIα, and two of them (26E5 and 26E8) targeted the K1 domain of TFPI and increased thrombin generation in the plasma of patients with HA. Both sdAbs impaired the ability of rhTFPIα to inhibit FXa and TF/FVIIa, in the absence and presence of their physiological modulators (protein S and FXa, respectively). These sdAbs efficiently increased thrombin generation in HB and FXI-deficient plasmas.Our large synthetic library could be used for readily generating diverse and functionally relevant anti-TFPI sdAbs that may be therapeutically attractive.
2026-06-23 | Nonacog Beta Pegol (N9-Gp) Prophylaxis in Pediatric Patients with Severe Hemophilia B: A Single Center Real World Experience.
Hemophilia B (Christmas disease) is a rare genetic bleeding disorder. Frequent FIX prophylaxis is challenging in pediatric patients because of difficult venous access and pain during factor administration. Nonacog beta pegol (N9-GP) is an extended half-life (EHL) recombinant FIX. The study assessed the efficacy of Nonacog beta pegol (N9-GP) in reducing bleeding episodes and its safety as prophylaxis in pediatric patients. The primary end-point was reduction in Annual bleeding rates (ABR) and Annual Joint bleeding rates (AJBR). The secondary objectives were to assess the days of school absenteeism, number of emergency visits, measurement of Hemophilia Joint Health Score (HJHS) 2.1 score, pediatric Hemophilia Activities List (pedHAL) score, development of inhibitor against FIX during treatment, and safety & adverse effects (AEs) profile. Ten pediatric patients managed with on-demand SHL FIX were included in the study. Their median age at study entry was 3 years (range, 1-13 years). The median duration of follow-up was 12 months (range, 6-60 months). They were subsequently started on N9-GP prophylaxis, and the mean duration of follow-up was 24 months (range, 11-30 months). There was a significant reduction in ABR (p-value, 0.002), AJBR (p-value, 0.022), and improvement in HJHS, pedHAL score, and reduction in school absenteeism in these children. Four patients experienced bleeding, which required treatment. Two patients developed an inhibitor to N9-GP. Mild adverse effects were noted in 20% of the patients. N9-GP prophylaxis compared to PD/r FIX replacement is a safe and effective strategy in prevention of bleeds, improving QOL and reducing joint related disability in pediatric patients with Hemophilia B.
2026-07-07 | Real-World Outcomes of Prophylaxis With rIX-FP in Germany: A Prospective, Non-Interventional Study in Haemophilia B.
Efficacy and safety of albutrepenonacog alfa (rIX-FP) in people with haemophilia B (PwHB) has been previously demonstrated in clinical trials. However, real-world data insights are required. To describe real-world effectiveness and tolerability of rIX-FP in PwHB in Germany. Prospective, non-interventional study conducted across 19 sites in Germany. Patients of any age treated with rIX-FP were enrolled between March 2018 and February 2024. Patients were monitored every 3-12 months and followed-up for 3 years or until ≥100 exposure days. To our knowledge, this is the largest study of factor replacement therapy in PwHB in Germany to date. Of the patients who completed the study (63/73), most (80.8%) had moderate or severe haemophilia B. The mean (standard deviation) duration of observation was 30.5 (8.32) months. For any prophylaxis regimen, the median (range) annualised bleeding rate (ABR) was 0.89 (0.0-9.6) and annualised spontaneous bleeding rate (AsBR) was 0.08 (0.0-5.2). The median ABR was 1.12, 0.68 and 0.13, and the median AsBR was 0.17, 0.00 and 0.06 for those treated with a 7-, 10- or 14-day regimen, respectively. Investigators rated the overall haemostatic effectiveness as 'good' or 'excellent' in 94% of cases (based on the worst assessment). Overall, 82 adverse events in 34 patients were reported, none were considered related to rIX-FP. This multicentre, non-interventional study in Germany demonstrates that rIX-FP prophylaxis is effective and well tolerated in PwHB of all ages in routine clinical practice and reinforces the results of the clinical trials.
2026-06-30 | Anti-TFPI Single-Domain Antibodies: Novel Rebalancing Therapies for Hemophilia and Other Rare Bleeding Disorders
Tissue factor pathway inhibitor (TFPI) is an important determinant of thrombin generation in patients with deficiency in factor (F)VIII, FIX, and FXI. As such, anti-TFPI monoclonal antibodies such as concizumab have been developed to treat hemophilia A (HA) and B (HB).The objective of this study is to generate single-domain antibodies (sdAbs) as a novel class of pharmacological agents blocking TFPI and increasing thrombin generation in the plasma of patients with severe HA, HB, and FXI deficiency.A large synthetic library of sdAbs was generated and selected by phage-display on recombinant human TFPIα (rhTFPIα). Anti-TFPI sdAbs were screened on their ability to promote thrombin generation. Their binding to the Kunitz (K1, K2, K3) domains of TFPIα were measured by enzyme-linked immunosorbent assay. Their effects on the inhibitory activity of rhTFPIα toward FXa and TF/FVIIa complex were tested in purified systems. Thrombin generation was measured on plasmas from patients with severe HA, HB, or FXI-deficiency spiked with the anti-TFPI sdAbs.A total of 14 out of 188 screened sdAbs specifically bound to rhTFPIα, and two of them (26E5 and 26E8) targeted the K1 domain of TFPI and increased thrombin generation in the plasma of patients with HA. Both sdAbs impaired the ability of rhTFPIα to inhibit FXa and TF/FVIIa, in the absence and presence of their physiological modulators (protein S and FXa, respectively). These sdAbs efficiently increased thrombin generation in HB and FXI-deficient plasmas.Our large synthetic library could be used for readily generating diverse and functionally relevant anti-TFPI sdAbs that may be therapeutically attractive.
2026-06-23 | Nonacog Beta Pegol (N9-Gp) Prophylaxis in Pediatric Patients with Severe Hemophilia B: A Single Center Real World Experience.
Hemophilia B (Christmas disease) is a rare genetic bleeding disorder. Frequent FIX prophylaxis is challenging in pediatric patients because of difficult venous access and pain during factor administration. Nonacog beta pegol (N9-GP) is an extended half-life (EHL) recombinant FIX. The study assessed the efficacy of Nonacog beta pegol (N9-GP) in reducing bleeding episodes and its safety as prophylaxis in pediatric patients. The primary end-point was reduction in Annual bleeding rates (ABR) and Annual Joint bleeding rates (AJBR). The secondary objectives were to assess the days of school absenteeism, number of emergency visits, measurement of Hemophilia Joint Health Score (HJHS) 2.1 score, pediatric Hemophilia Activities List (pedHAL) score, development of inhibitor against FIX during treatment, and safety & adverse effects (AEs) profile. Ten pediatric patients managed with on-demand SHL FIX were included in the study. Their median age at study entry was 3 years (range, 1-13 years). The median duration of follow-up was 12 months (range, 6-60 months). They were subsequently started on N9-GP prophylaxis, and the mean duration of follow-up was 24 months (range, 11-30 months). There was a significant reduction in ABR (p-value, 0.002), AJBR (p-value, 0.022), and improvement in HJHS, pedHAL score, and reduction in school absenteeism in these children. Four patients experienced bleeding, which required treatment. Two patients developed an inhibitor to N9-GP. Mild adverse effects were noted in 20% of the patients. N9-GP prophylaxis compared to PD/r FIX replacement is a safe and effective strategy in prevention of bleeds, improving QOL and reducing joint related disability in pediatric patients with Hemophilia B.
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