| Indication | Haemophilia A (congenital FVIII deficiency), with or without inhibitors |
| Drug | denecimig |
| Mechanism of Action | FVIIIa mimetic bispecific antibody |
| Company | Novo Nordisk |
| Trial Phase | Phase 3 |
| Trial Acronym | FRONTIER |
| NCT ID | NCT05053139, NCT05306418, NCT05685238, NCT05878938 |
| Category | Regulatory Milestone |
| Sub Category | Approval Granted |
| Therapeutic Area | Hematology |
| Regulatory Agency | European Commission, European Medicines Agency, CHMP, US Food and Drug Administration |
| Approval Date | 13 November 2026 |
| Approved Market/Region | EU, Saudi Arabia |
| Dosing Regimens | once-monthly, once-every-two-weeks, once-weekly |
| Administration Method | subcutaneous injection, single-use pre-filled pen |
| Patient Population | adults and children with haemophilia A (congenital FVIII deficiency), with or without inhibitors |
| Comparator | prior clotting factor prophylaxis and on-demand treatment |
| Previous Therapy for Switching | emicizumab |
European Commission Approves Novo Nordisk's FREHEMGO for Hemophilia A
Novo Nordisk announced that the European Commission has granted marketing authorisation for FREHEMGO® (denecimig) for routine prophylaxis in adults and children with haemophilia A, with or without inhibitors. This approval offers unprecedented dosing flexibility with once-monthly, once-every-two-weeks, or once-weekly subcutaneous injections using a single-use pre-filled pen. The authorisation is based on the robust FRONTIER clinical trial programme, which demonstrated significant reductions in annualised bleeding rates compared to prior treatments and consistently low mean annualised bleeding rates across patient populations. FREHEMGO® is also approved in Saudi Arabia and under review by the US Food and Drug Administration (FDA).
- Comprehensive Clinical Evidence: The approval of FREHEMGO® is underpinned by the extensive FRONTIER clinical trial programme, including pivotal FRONTIER2 and FRONTIER3 trials. These studies consistently showed that denecimig significantly reduced annualised bleeding rates compared to previous clotting factor prophylaxis and on-demand treatments, with a substantial number of participants achieving zero treated bleeds across adult and paediatric populations, both with and without inhibitors.
- Unprecedented Dosing Flexibility: FREHEMGO® distinguishes itself by offering patients and healthcare providers a choice of once-monthly, once-every-two-weeks, or once-weekly subcutaneous dosing options. This flexibility, delivered via a single-use pre-filled pen, is designed to better integrate into patients' daily lives, reducing the burden of frequent administration and allowing for more personalised treatment decisions based on individual needs and lifestyles.
- Novel Mechanism of Action: Denecimig is a next-generation FVIIIa mimetic bispecific antibody that effectively 'mimics' the cofactor function of Factor VIIIa. By bridging Factor IXa and Factor X, it helps restore the body’s thrombin generation capacity, crucial for blood clot formation. This mechanism is effective for people with haemophilia A, regardless of whether they have developed inhibitors to traditional clotting factor replacement therapies.
Addressing Key Challenges in Haemophilia A Treatment
Current treatment for haemophilia A improves bleeding outcomes and long-term joint health, yet persistent challenges span immunogenicity, subclinical joint damage, and treatment burden. Early, sustained prophylaxis is effective, but a subset of patients still progresses, and newer factor and non-factor options introduce monitoring, adherence, and evidence gaps.
Inhibitor development remains the most significant complication, with neutralizing antibodies inactivating the procoagulant activity of FVIII and inhibiting response to replacement therapy. Reported incidence includes "25% to 30% of patients", "21% of 62" previously untreated patients with severe haemophilia A in Finland with 10 (16% of 62) with high titre, "18% of Argentine patients with severe haemophilia A (HA)", and "almost 30% of previously untreated patients (PUPs)". Major risk factors include disease severity, major FVIII gene defects, family history and non-Caucasian race, with additional roles for age at first treatment, intensity of early treatment, use of prophylaxis and product choice [especially recombinant vs. plasma-derived von Willebrand factor (VWF)-containing concentrates]. Intensity of early treatment appears to be a stronger risk factor than timing of first treatment, high-risk genotypes include multi-exon deletions [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2; 21% (7-59)], and history of a major bleed enhanced development (aHR, 4.0; 95% CI, 1.2-13.7).
Progressive arthropathy despite prophylaxis and limited long-term joint data for newer factors. A subset of patients appear to develop arthropathy despite maintaining excellent bleeding outcomes, which suggests possible recurrent asymptomatic bleeding into the joints, and limited data are available on how long-acting factor VIII and factor IX replacement therapies could impact long-term joint outcomes. Synovial changes detected by magnetic resonance imaging are a strong predictor for future development of hemophilic arthropathy, HEAD-US detected more abnormalities than HJHS, and synovitis was the most frequent abnormality while cartilage damage was infrequent and subchondral bone changes were negligible.
Burden of frequent intravenous infusion and adherence loss. Relatively short half-lives of factor (F) VIII and IX concentrates leads to need for frequent venous access, reduced patient adherence and negative longterm outcomes, with reported mean half-life extensions of 1.5-1.8 times that of standard products for FVIII. In tailored, frequency-escalated primary prophylaxis, median (range of values [ROV]) weekly adherence was 85.7% (37.4%-99.8%), with adherent weeks of 92.9% (50%-100%), 80.3 (32%-96%), and 72.6% (14%-98%) on steps 1 (weekly), 2 (twice weekly), and 3 (alternate-day), and bleeding risk reduced by 15% for each 10% increase in adherence during preceding 12 weeks (hazard ratio, 0.85; 95% confidence interval, 0.81-0.90). Continuous infusion aimed at median target FVIII level of 0.8 IU mL(-1) was haemostatically very effective with median incidence of postoperative bleeding of 1.8% and phlebitis in 2-11% of treatments.
Monitoring and perioperative gaps for emicizumab and non-factor therapies. Emicizumab, a bispecific monoclonal antibody administered subcutaneously, mimicking the action of activated coagulation factor VIII, achieved an annualized bleeding rate (ABR) of zero in 73% of inhibitors patients, with haemostasis satisfactory in 93.7% of minor and 90.7% of major surgical procedures. Unmet needs include establishment of treatment guidelines for surgery and breakthrough bleeding, limited expertise, especially in young children, and availability of laboratory assays, with chromogenic FVIII assay only available in 73% of centres and inhibitor titers monitored in 78.4% of inhibitor patients. Factor VIII (FVIII) or factor IX (FIX) assays are no longer adequate for non-factor therapies, which all increase thrombin generation with thrombosis as main adverse effect when too much thrombin is formed, requiring thrombin generation assay (TGA) to optimize bypassing therapy, detect hypercoagulability, and assess efficacy and safety of combined therapies including non-factor therapies with bypassing agents or FVIII/FIX concentrates.
Insufficient evidence in moderate disease and economic/choice uncertainty. Severity classification alone is insufficient to predict bleeding tendency, with joint bleeding and joint injury observed in moderate disease and variation such that patients with moderate disease may have a severe phenotype. Few studies have specifically assessed outcomes associated with prophylaxis in patients with moderate haemophilia A, although prophylaxis with FVIII concentrates and non-factor treatments (i.e. emicizumab) provides beneficial effects in bleeding frequency and joint health. Long-acting concentrates raise cost repercussions and questions regarding how decisions about choosing one longer acting concentrate over another, and whether these products are interchangeable, are made.
FREHEMGO® Targets Evolving Unmet Needs in Haemophilia A
Recent literature in congenital haemophilia A targets persistent gaps despite prophylaxis, including inhibitor development in previously untreated patients, breakthrough bleeding and joint morbidity, and burden on quality of life and productivity. Gene therapy and optimized prophylaxis strategies are being evaluated to address freedom from infusions and long-term joint protection.
Previously untreated patients (PUPs) with severe haemophilia A (FVIII <1%): An open-label, phase 3, extension study of rVIII-SingleChain in 24 PUPs (median age 1 year [range 0-5]) reported six PUPs developed a HT inhibitor (>5 BU/mL) and six developed a LT inhibitor (≤5 BU/mL), with median number of exposure days at inhibitor development was 10 (interquartile range [IQR] 5.0-14.0). Of 11 inhibitor-positive PUPs who continued rVIII-SingleChain therapy, nine (81.8%; three HT, six LT) achieved inhibitor eradication (<0.6 BU/mL) with median time to eradication was 14.3 weeks (IQR 9.8-53.8).
Patients with FVIII inhibitors requiring immune tolerance induction (ITI): The Hemophilia Inhibitor Previously Untreated Patient (PUP) Study (HIPS) extension arm (HIPS-ITI) evaluated ITI with the same FVIII product until successful tolerance, declared failure, or a maximum of 2 years, with ITI successful or partially successful in 2 patients and failed in 3. The ReITIrate phase IV, open-label, single-arm study evaluated rescue ITI with efmoroctocog alfa within 60 weeks in severe haemophilia A patients who failed previous ITI attempts, with one subject attaining all 3 ITI success criteria after 46 weeks. Carriers of F8 large deletions and small insertions/deletions had higher odds of ITI failure versus intron 22 inversion (odds ratio [OR] 15.50; 95% confidence interval [95% CI] 4.59-71.30 and 4.25 times higher [95% CI, 1.53-12.3]).
Patients with breakthrough bleeding and haemophilia-affected joints (HAJs) despite prophylaxis: In 211 participants in the PicnicHealth database, 63 participants (70.8%) receiving SHL, 43 (61.4%) EHL and 36 (62.1%) emicizumab had ≥1 bleed at Year 1. In 351 eligible patients in France, Germany, Italy, Spain and the UK, 209 (59.5%) patients had HAJs, with pain/discomfort reported in 85.7% vs 53.3% and mean EuroQol Visual Analogue Scale score 65.5 (19.3) vs 81.1 (14.6). Since switching to current prophylactic treatment, 48% of haemophilia A patients had experienced one or more episodes of breakthrough bleeding, with joint bleeds in 53% of haemophilia A patients.
Patients with impaired health-related quality of life, mental health and work productivity: Among 350 PwSHA in the CHESS Data Platform, anxiety GAD-7 mean scores 6.0 vs 7.3 and depression PHQ-8 mean scores 6.8 vs 7.8 were reported for emicizumab vs FVIII prophylaxis, with work impairment 31% vs 50%. In HemiNorth 2, model-based ABRs for treated bleeds decreased from 5.9 (95% confidence interval [CI]: 3.8-9.1) to 1.6 (95% CI: 0.9-3.0) after switching from FVIII prophylaxis to emicizumab, and 23 of 25 (92.0%) preferred emicizumab over FVIII prophylaxis.
Adult males with severe haemophilia A receiving FVIII prophylaxis targeted for gene therapy: In the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial in 134 adult males, mean annualized bleeding rate for treated bleeds decreased from 4.8 (SD, 6.5) bleeds/y at baseline to 0.8 (SD, 2.3) bleeds/y after prophylaxis and 0.97 (SD, 3.48) bleeds/y during year 3, with annualized FVIII utilization decreased 96.8% after prophylaxis and 94.2% during year 3. Challenges include hepatotoxicity, immune response, durability with mean and median FVIII activity 18.4 (SD, 30.8) and 8.3 IU/dL at week 156, and eligibility restrictions due to preexisting neutralizing antibodies.
The FRONTIER Program: Clinical Evidence for Denecimig
Recent trials in congenital haemophilia A evaluate factor replacement, non-factor prophylaxis and inhibitor eradication strategies in patients with or without inhibitors. Designs include prospective randomised, open-label and observational studies ranging from small single-centre cohorts to large multinational phase 3 trials. Primary endpoints centre on annualised bleeding rates, haemostatic efficacy and safety including inhibitor development and thromboembolic events.
| Trial / Population | Design | Intervention / Comparator | Key Endpoints |
|---|---|---|---|
| explorer8 - male, aged 12 years or older, with congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors | Prospective, multicentre, open-label, randomised, phase 3a trial at 69 investigational sites in 31 countries, patients randomly assigned 1:2 to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2) | Subcutaneous concizumab at 1.0 mg/kg loading dose on day 1 and subsequent daily doses of 0.20 mg/kg from day 2, with options to decrease to 0.15 mg/kg, stay on 0.20 mg/kg, or increase to 0.25 mg/kg | Number of treated spontaneous and traumatic bleeding episodes; estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0.14 (95% CI 0.07-0.29; p<0.0001) for patients with haemophilia A; safety including SARS-CoV-2 infection, increase in fibrin D-dimers, upper respiratory tract infection |
| ATLAS-A/B - male participants aged at least 12 years with severe haemophilia A or B without inhibitors, previously treated on-demand with clotting factor concentrates | Multicentre, open-label, randomised phase 3 study at 45 sites in 17 countries, randomly assigned in a 2:1 ratio for 9 months | 80 mg subcutaneous fitusiran prophylaxis once per month or continue on-demand clotting factor concentrates | Annualised bleeding rate; median annualised bleeding rate was 0.0 (0.0-3.4) in the fitusiran group and 21.8 (8.4-41.0) in the on-demand group; estimated mean annualised bleeding rate 3.1 [95% CI 2.3-4.3] vs 31.0 [21.1-45.5], rate ratio 0.101 [95% CI 0.064-0.159], p<0.0001; safety including increased alanine aminotransferase concentration and treatment-emergent serious adverse events |
| FRONTIER5 (NCT05878938) - patients aged ≥12 years with HA with or without factor VIII inhibitors | 26-week, single-arm, open-label, phase 3b study, direct switch without washout period or loading dose | Transitioned directly from emicizumab to denecimig maintenance doses administered subcutaneously once-every week, once-every-two-weeks, or once-every-month by pen-injector | Number of treatment-emergent adverse events; thrombin generation, patient-reported pen-injector experience, treatment burden, joint pain, and physical activity; TEAEs in 70.5% of patients (3.48 per patient-year of exposure); no thromboembolic events, hypersensitivity reactions, or clinical evidence of neutralising anti-denecimig antibodies |
| CAGUYAMA - 100 people with hemophilia A (aged ≥4 years) receiving emicizumab at 13 centers in Japan | Multicenter, open-label, nonrandomized clinical trial | FVIII (standard or extended half-life) at target dose of 30 IU/kg (allowable range, 25-35 IU/kg) for eligible bleeding or surgical events; paired blood samples pre- and post-FVIII | Change in clot waveform analysis-adjusted maximum coagulation rate, expressed as IMCR% relative to pooled normal plasma; peak thrombin in thrombin generation assay, rotational thromboelastometry, clinical hemostasis, and safety; clot waveform analysis-adjusted maximum coagulation rate increased from 39.4% to 92.1% post-FVIII; all events achieved effective hemostasis |
| guardian 1 - 150 patients (24 adolescents and 126 adults) with severe haemophilia A (FVIII activity ≤1%), with at least 150 exposure days to any FVIII product and no history of inhibitors | Multinational, open-label, non-controlled trial | Prophylaxis with turoctocog alfa for approximately 6 months, mean of 85 EDs during trial | Safety; FVIII inhibitors, adverse events; efficacy including 499 bleeding episodes, success rate defined as 'excellent' or 'good' haemostatic response was 81%, overall median annualized bleeding rate was 3.7 (interquartile range: 8.7) bleeds/patient/year |
| ASPIRE (NCT01454739) - subjects with severe haemophilia A who completed A-LONG and Kids A-LONG | Open-label extension study | Individualized prophylaxis (IP), weekly prophylaxis, modified prophylaxis or episodic treatment with recombinant factor VIII Fc fusion protein (rFVIIIFc) | Inhibitor development; annualized bleed rates; median treatment duration 3.9 (0.1-5.3) years and 3.2 (0.3-3.9) years; no inhibitors observed (0 per 1000 subject-years; 95% confidence interval, 0-5.2); median overall ABR for adults and adolescents was <1.0 |
| LEOPOLD II - males aged 12-65 years with severe haemophilia A receiving on-demand treatment, subanalysis 23 Chinese and 57 non-Chinese patients | Randomised trial, assigned to low-dose prophylaxis (20-30 IU/kg twice-weekly), high-dose prophylaxis (30-40 IU/kg 3 times weekly) or on-demand for 1 year | BAY 81-8973 (Kovaltry) prophylaxis vs on-demand | Annualized bleeding rates and safety; median ABRs for all bleeds in last 6 months were 2.0 and 1.0 for Chinese and non-Chinese patients in combined prophylaxis groups, and 61.3 and 58.5 in on-demand group; no patients developed FVIII inhibitors |
| Emicizumab in Children - pediatric patients aged 1 mo to 12 y with severe HA and frequent / life threatening bleeding events, with or without factor VIII inhibitors (n=18) | Observational pre-post study, switched from on-demand or prophylactic factor VIII/bypassing agents/immune tolerance induction to emicizumab prophylaxis and followed for 52 wk | Emicizumab prophylaxis | Annualized bleeding rate and annualized joint bleeding rate; mean annualized bleeding rate reduced from 12.7 ± 8.61 to 0.28 ± 0.46 (p<0.001); mean annualized joint bleeding rate reduced from 9.72 ± 7.44 to 0.17 ± 0.38 (p<0.001); target joint resolution was 100% |
| Immune tolerance induction trial - 115 paediatric participants with severe haemophilia A and high-responding inhibitors, first attempt at immune tolerance induction | Multinational randomised controlled trial | Low dose (50 IU/kg factor VIII concentrate three times per week) vs high dose (200 IU/kg factor VIII daily) | Immune tolerance induction success, infection, bleeding episodes; 24 out of 58 participants (46.6%) in low-dose and 22 out of 57 (38.6%) in high-dose experiencing full tolerance, risk ratio 1.07 (95% CI 0.68 to 1.68); bleeding events in 50 out of 58 (86.2%) vs 36 out of 57 (63.1%), risk ratio 1.36 (95% CI 1.09 to 1.71) |
Denecimig's Role in the Evolving Haemophilia A Landscape
Valoctocogene roxaparvovec, an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A, has demonstrated durable haemostatic control in the phase 1/2 trial NCT02576795 in males ≥18 years with severe HA (factor VIII [FVIII] ≤1 IU/dL) without history of FVIII inhibitors or anti-AAV5 antibodies. In participants receiving 6 × 10 vg/kg (n = 7) and 4 × 10 vg/kg (n = 6), mean annualized treated bleeds and exogenous FVIII infusion rates were ≥88% lower than baseline values during all follow-up, with mean (median) FVIII activity (chromogenic assay) of 16.2 (10.3) and 6.7 (7.2) IU/dL at years 7 and 6, corresponding to mild haemophilia. In final 7-year results for the 4 × 10 vg/kg cohort, mean FVIII activity peaked within year 1 (week 52 FVIII, 21.1 IU/dL) and decreased to 4.2 IU/dL at the end of year 7, mean ABR declined 87% from baseline to 1.6 bleeds/year and mean annualized FVIII use declined 93% to 10.3 infusions/year, with 3/5 participants remaining off prophylaxis and no participants developing FVIII inhibitors or having thromboembolic events. A matching-adjusted indirect comparison (MAIC) of 6 × 10 vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270-902) in severe haemophilia A (FVIII ≤1 IU/dL) reported ABR for all bleeds statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33-.93]), with significantly higher proportions with no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20-6.31]) and no treated bleeds (3.25 [1.53-6.90]).
Efanesoctocog alfa, a novel, "ultra-extended half-life" FVIII concentrate and first-in-class high-sustained FVIII replacement therapy, has shifted prophylaxis to once-weekly efanesoctocog alfa (50 IU/kg) dosing. In the Phase 3 XTEND-1 trial (NCT04161495), once-weekly prophylaxis achieved high-sustained factor levels in the normal to near-normal range (>40%) for most of the week, and in participants switching from marketed standard half-life (SHL) or extended half-life (EHL) FVIII prophylaxis, significant reduction in ABR from 2.96 to 0.69 (p < 0.0001) was observed with reductions in spontaneous, traumatic, joint and spontaneous joint ABRs (p < 0.0001), with mean weekly injection frequency from 2.8 to 1.0 in the SHL cohort (p < 0.0001) and from 1.8 to 1.0 in the EHL cohort (p < 0.0001). MAICs using XTEND-1 data reported efanesoctocog alfa once-weekly (Q1W) associated with significantly lower ABRs for any (incidence rate ratio [95% CI] 0.33 [0.20; 0.53]), any treated (0.49 [0.30; 0.80]) and treated joint (0.51 [0.28; 0.91]) bleeds compared with emicizumab Q1W, and with significantly lower ABRs for any [mean difference (95% CI) - 2.24 (- 3.24; - 1.25)], spontaneous [- 1.52 (- 2.33; - 0.72)], and joint bleeds [- 1.60 (- 2.32; - 0.88)] versus EHL therapies (rurioctocog alfa pegol, efmoroctocog alfa, turoctocog alfa pegol, damoctocog alfa pegol) and for any [- 3.61 (- 4.43; - 2.79)], treated [- 1.55 (- 1.89; - 1.20)], spontaneous [- 2.52 (- 3.31; - 1.72)], and joint bleeds [- 3.42 (- 4.77; - 2.08)] versus SHL therapies. In XTEND-Kids (NCT04759131) in previously treated children <12 years with severe haemophilia A, once-weekly prophylaxis provided high-sustained FVIII levels in the normal to near-normal range (>40 IU/dL) for 3 days and >10 IU/dL for ∼7 days at steady state, with zero bleeds in 64% of participants, a single dose resolving 95% of bleeding episodes, and haemostatic efficacy rated as excellent or good for nearly all evaluated first injections (97%).
Non-factor prophylaxis by subcutaneous administration has expanded options with and without inhibitors. Emicizumab, a recombinant humanized bispecific antibody that bridges factor IXa and factor X to mimic the cofactor function of factor VIII, showed in the UK Haemophilia Centre Doctors' Organisation follow-up in persons with haemophilia A with inhibitors a mean ABR of .32 (95% CI, .18; .39) over median 42 months, with within-person comparison (n = 74) demonstrating an 89% reduction in ABR after switching and increase in zero treated bleed rate from 45 to 88% (p < .01). Fitusiran, a subcutaneous small interfering RNA therapeutic targeting antithrombin to rebalance haemostasis, in ATLAS-INH (NCT03417102) in men, boys, and young adults aged 12 years or older with severe haemophilia A or B with inhibitors reported negative binomial model-based mean ABR of 1·7 [95% CI 1·0-2·7] versus 18·1 [10·6-30·8] with bypassing agents on-demand, corresponding to 90·8% (95% CI 80·8-95·6) reduction (p<0·0001), with 25 (66%) having zero treated bleeds versus one (5%), and in ATLAS-A/B (NCT03417245) without inhibitors estimated mean ABR of 3·1 [95% CI 2·3-4·3] versus 31·0 [21·1-45·5] with on-demand clotting factor (rate ratio 0·101 [95% CI 0·064-0·159]; p<0·0001). Concizumab, an anti-tissue factor pathway inhibitor monoclonal antibody as once-daily subcutaneous prophylaxis, in explorer8 (NCT04082429) in males aged 12 years or older with congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors reported estimated mean ABR ratio for treated spontaneous and traumatic bleeding episodes of 0·14 (95% CI 0·07-0·29; p<0·0001) for haemophilia A and 0·21 (0·10-0·45; p<0·0001) for haemophilia B versus no prophylaxis.
Frequently Asked Questions
References
- [1] Mancuso ME, Croteau SE et al.. Benefits and risks of non-factor therapies: Redefining haemophilia treatment goals in the era of new technologies. Haemophilia : the official journal of the World Federation of Hemophilia. 2024 Apr. 38481077
- [2] Måseide RJ, Berntorp E et al.. Health-related quality of life and physical activity in Nordic patients with moderate haemophilia A and B (the MoHem study). Haemophilia : the official journal of the World Federation of Hemophilia. 2024 Jan. 37983883
- [3] Chowdary P, Angchaisuksiri P et al.. Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial. The Lancet. Haematology. 2024 Dec. 39521008
- [4] Miesbach W. Gene Therapy of Haemophilia: Current Status and Future Directions. Hamostaseologie. 2026 Feb. 41702383
- [5] Paul H, Berg V et al.. Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication. Blood advances. 2023 May 9. 36074992
- [6] Arvanitakis A, Jepsen C et al.. Primary prophylaxis implementation and long-term joint outcomes in Swedish haemophilia A patients. Haemophilia : the official journal of the World Federation of Hemophilia. 2024 May. 38575549
- [7] Susen S, Trossaërt M et al.. A phase 1, open-label study to assess the pharmacokinetics, safety, and tolerability of a single intravenous injection of efanesoctocog alfa in adults with type 2N or type 3 von Willebrand disease. Journal of thrombosis and haemostasis : JTH. 2026 Jan. 40685140
- [8] Mahlangu J, Mancuso ME et al.. Extension Study With rVIII-SingleChain in Previously Untreated Patients (PUPs) With Severe Haemophilia A. Haemophilia : the official journal of the World Federation of Hemophilia. 2025 Mar. 39917944
- [9] Radhakrishnan N, Pandharipande A et al.. Freedom From Bleeds With Low-Dose Emicizumab Prophylaxis in Inhibitor-Positive Hemophilia A. Journal of hematology. 2024 Oct. 39493600
- [10] Prezotti AN, Rocha DM et al.. Annualized bleeding rate in hemophilia A patients in Brazil: a systematic review. Hematology, transfusion and cell therapy. 2025 Apr-Jun. 40156956
- [11] Young G, Srivastava A et al.. Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial. Lancet (London, England). 2023 Apr 29. 37003287
- [12] Josset L, Rezigue H et al.. Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies. International journal of laboratory hematology. 2025 Apr. 39660815
- [13] Jiang D, Johnston N et al.. Integration of Efanesoctocog Alfa in Clinical Practice for Children, Adolescents, and Young Adults With Severe Haemophilia A. Haemophilia : the official journal of the World Federation of Hemophilia. 2026 Mar-Apr. 41403339
- [14] Zuccherato LW, Souza RP et al.. Large deletions and small insertions and deletions in the factor VIII gene predict unfavorable immune tolerance induction outcome in people with severe hemophilia A and high-responding inhibitors. Thrombosis research. 2024 Oct. 39186847
- [15] Glasner MF, Pipe S et al.. Gene-based therapies for hemophilia. Research and practice in thrombosis and haemostasis. 2025 May. 40488175
- [16] Baghaipour M, Salimi T et al.. Tailored prophylaxis in children with severe hemophilia: A four-year Iranian study. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2021 Dec. 34257016
- [17] Astermark J, Ranta S et al.. Health-Related Quality of Life, Physical Activity and Joint Health in People With Severe Haemophilia A Receiving Emicizumab: Results From the Phase IV HemiNorth 2 Study. Haemophilia : the official journal of the World Federation of Hemophilia. 2025 Nov. 40898745
- [18] Dettoraki A, Michalopoulou A et al.. Clinical application of extended half-life factor VIII in children with severe haemophilia A. Haemophilia : the official journal of the World Federation of Hemophilia. 2022 Jul. 35503081
- [19] Batorova A, Holme P et al.. Continuous infusion in haemophilia: current practice in Europe. Haemophilia : the official journal of the World Federation of Hemophilia. 2012 Sep. 22530687
- [20] Chai-Adisaksopha C, Nevitt SJ et al.. Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors. The Cochrane database of systematic reviews. 2017 Sep 25. 28944952
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