"Haemophilia B"

Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B Technology appraisal guidance Published: 24 July 2024 www.nice.org.uk/guidance/ta989 © NICE 2024. All rights reserved. Subject to Notice of rights ( responsibility The recommendations in this guidance represent the view of NICE, arrived inequalities. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Etranacogene dezaparvovec for treating moderately severe or severe haemophilia B(TA989)© NICE 2024. All rights reserved. Subject to Notice of rights ( 2 of24 Contents 1

Etranacogene dezaparvovec for the treatment of Haemophilia B

 Anne Hüning  Michaela Florina Kerekes  Christopher Kunigkeit  Fabian Lotz  Katrin Nink  Min Ripoll Keywords Nonacog beta pegol, Hemophilia B, Child, Benefit Assessment Extract of dossier assessment A23-90 Version 1.0 Nonacog beta pegol ( haemophilia B, patients < 12 years) 28 November 2023 Institute for Quality and Efficiency in Health Care (IQWiG) - I.1 - Part I: Benefit assessment Extract Nonacog beta pegol (haemophilia B, children < 12 years) ' Benefit assessment according to '35a Social Code Book V 1 Translation of Sections I 1 to I 6 of the dossier assessment Nonacog beta pegol (Hämophilie B, Patientinnen und Patienten < 12 Jahre) – Nutzenbewertung gemäß § 35a SGB V. Please note: This document was translated by an external translator and is provided as a service by IQWiG

in the present dossier assessment. IQWiG employees involved in the dossier assessment  Christina Frings  Moritz Felsch  Tatjana Hermanns  Katrin Nink  Min Ripoll  Veronika Schneck  Ulrike Seay  Kathrin Wohlhöfner Keywords Eftrenonacog alfa, Hemophilia B, Benefit Assessment Extract of dossier assessment A23-77 Version 1.0 Eftrenonacog alfa ( haemophilia B) 18 October 2023 Institute for Quality Eftrenonacog alfa (haemophilia B) ' Benefit assessment according to '35a Social Code Book V 1 Translation of Sections I 1 to I 6 of the dossier assessment Eftrenonacog alfa (Hämophilie B) – Nutzenbewertung gemäß § 35a SGB V. Please note: This document was translated by an external translator and is provided as a service by IQWiG to English-language readers. However, solely the German original

Etranacogene dezaparvovec (Hemgenix) - haemophilia B Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands An agency of the European Union Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2023. Reproduction is authorised provided the source is acknowledged. EMA/45357/2023 EMEA/H/C/004827 Hemgenix (etranacogene dezaparvovec) An overview of Hemgenix and why it is authorised in the EU What is Hemgenix and what is it used for? Hemgenix is a medicine used to treat adults with severe and moderately severe haemophilia B, an inherited bleeding disorder caused by the lack of factor IX (a protein needed to produce blood clots

Fidanacogene Elaparvovec (Beqvez) - hemophilia B (congenital Factor IX deficiency) Return to Article DetailsFidanacogene Elaparvovec (Beqvez)

Fidanacogene Elaparvovec (Beqvez) - Hemophilia B View of Fidanacogene Elaparvovec (Beqvez) | Canadian Journal of Health TechnologiesReturn to Article DetailsFidanacogene Elaparvovec (Beqvez)

Etranacogene Dezaparvovec (Hemgenix) - Hemophilia B (congenital factor IX deficiency) View of Etranacogene Dezaparvovec (Hemgenix) | Canadian Journal of Health TechnologiesReturn to Article DetailsEtranacogene Dezaparvovec (Hemgenix)

. Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial. Lancet Haematol 2024; 11(4):e265-e275. 6. Pipe S, van der Valk P, Verhamme P, Kampmann P, Leebeek F, Coppens M et al. Long-term bleeding protection, sustained FIX activity, reduction of FIX consumption and safety of Hemophilia B gene therapy: results in hemophilia B: a multinational randomized phase 3 trial. Blood. 2014;124(26):3880-6. 12. Lambert T, Recht M, Valentino LA, Powell JS, Udata C, Sullivan ST, et al. Reformulated BeneFix: efficacy and safety in previously treated patients with moderately severe to severe haemophilia B. Haemophilia. 2007;13(3):233-43. 13. Klamroth R, Bonner A, Gomez K, Monahan PE, Szafranski K, Zhang X, et al. Indirect

Summary of COHERE Finland's recommendation on etranacogene dezaparvovec (AMT-061) in the treatment of haemophilia B SUMMARY 1(3) 23 September 2024 STM023:00/2023 VN/25788/2023 The Council for Choices in Health Care in Finland PO BOX 33 (Meritullinkatu 8, Helsinki) 00023 GOVERNMENT, Finland Tel 358 295 16001 www.palveluvalikoima.fi palveluvalikoima.stm@gov.fi RECOMMENDATION ON ETRANACOGENE DEZAPARVOVEC (AMT-061) IN THE TREATMENT OF HAEMOPHILIA B At its meeting of 23 Septembet 2024, the Council for Choices in Health Care in Finland (COHERE Finland) adopted a recommendation on etranacogene dezaparvovec (AMT-061) in the treatment of Haemophilia B. Etranacogene dezaparvovec (AMT-061), which is a gene therapy medicinal product, is not included in the national range of services for treating severe

Schierbaum  Sonja Schiller Keywords: Albutrepenonacog alfa, Hemophilia B, Benefit Assessment Extract of dossier assessment A21-137 Version 1.0 Albutrepenonacog alfa (haemophilia B) 11 January 2022 Institute for Quality and Efficiency in Health Care (IQWiG) - iii - Table of contents Page List of tables , Lubetsky A et al. Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients. Haemophilia 2015; 21(6): 784-790. https://dx.doi.org/10.1111/hae.12721. 5. Santagostino E, Martinowitz U, Lissitchkov T et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results

Summary - Rebinyn ' Prophylaxis in children and adolescents with hemophilia B Rebinyn™ – Prophylaxis in children and adolescents with hemophilia B English summary Une production de l’Institut national d’excellence en santé et en services sociaux (INESSS) FEBRUARY 2023 1 SUMMARY Rebinyn™ – Prophylaxis in children and adolescents with hemophilia B Mandate prophylaxis in adults and children with hemophilia B (congenital FIX deficiency, otherwise known as Christmas disease). This evaluation concerns the use of nonacog beta pegol “as routine prophylaxis in children and adolescents under 18 years of age with hemophilia B to prevent or reduce the frequency of bleeding episodes.” Nonacog beta pegol was previously evaluated twice by INESSS for occasional use

Gene Therapy for Hemophilia B and An Update on Gene Therapy for Hemophilia A: Effectiveness and Value ©Institute for Clinical and Economic Review, 2022 Gene Therapy for Hemophilia B and An Update on Gene Therapy for Hemophilia A: Effectiveness and Value Final Evidence Report Posted December 22, 2022 Prepared for ©Institute for Clinical and Economic Review, 2022 Page i Final Evidence care manufacturers or insurers. DATE OF PUBLICATION: December 22, 2022 How to cite this document: Tice JA, Walton S, Herce-Hagiwara B, Fahim SM, Moradi A, Sarker J, Chu J, Agboola F, Pearson SD, Rind DM. Gene Therapy for Hemophilia B and An Update on Gene Therapy for Hemophilia A: Effectiveness and Value; Evidence Report. Institute for Clinical and Economic Review, December 22, 2022. https

Fidanacogene Elaparvovec for Hemophilia B - A Multiyear Follow-up Study. Treatment with fidanacogene elaparvovec, a recombinant adeno-associated virus (AAV) vector developed for the treatment of hemophilia B, led to sustained expression of the high-activity factor IX variant (FIX-R338L, or FIX-Padua) in a phase 1-2a study. The long-term safety and efficacy of this treatment are not known . In a 12-month study, 15 participants with severe or moderately severe hemophilia B (factor IX coagulant activity, ≤2% of the normal value) received fidanacogene elaparvovec at a dose of 5×10 vector genomes (vg) per kilogram of body weight; thereafter, participants could enroll in a 5-year follow-up study. Safety end points included adverse events and changes in laboratory measures. Efficacy end points

Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B. Fidanacogene elaparvovec, an adeno-associated virus (AAV) gene-therapy vector for hemophilia B containing a high-activity human factor IX variant (FIX-R338L/FIX-Padua), was associated with sustained factor IX activity in a phase 1-2a study. We conducted a phase 3 open-label study of fidanacogene elaparvovec at a dose of 5×10 vector genome copies per kilogram of body weight. Men 18 to 65 years of age with hemophilia B and a factor IX level of 2% or less were eligible for screening if they had received at least 6 months of therapy with prophylactic factor IX concentrate. The primary end point, tested for noninferiority, was the annualized bleeding rate (treated and untreated bleeding episodes) from week 12 to month 15 after

A transposable element prevents severe hemophilia B and provides insights into the evolution of new- and old world primates. Alu-elements comprise a large part of the human genome and some insertions have been shown to cause diseases. Here, we illuminate the protective role of an Alu-element in the 3'UTR of the human Factor 9 gene and its ability to ameliorate a poly(A) site mutation in a hemophilia B patient, preventing him from developing a severe disease. Using a minigene, we examined the disease-causing mutation and the modifying effect of the transposon in cellulo. Further, we simulated evolutionary scenarios regarding alternative polyadenylation before and after Alu insertion. A sequence analysis revealed that Old World monkeys displayed a highly conserved polyadenylation sites

The frequency of complications in a cohort of patients diagnosed with hemophilia A and hemophilia B receiving prophylactic treatment in Colombia: A retrospective noninterventional study. Hemophilia A and B are disorders associated with the deficit of coagulation factors VIII and IX. Was to determine the incidence of complications in a cohort of patients diagnosed with moderate and severe and hospitalizations were evaluated. A total of 159 male patients were identified with hemophilia A (n = 140; 88.1%) and B (n = 19; 11.9%) with a mean follow-up of 5.9±2.3 years. The mean age was 23.6±16.1 years, hemophilia was reported as severe in 125 patients in hemophilia A (89.3%) and 13 patients in hemophilia B (68.4%). Primary prophylaxis was registered in 17.0% of patients, 44.7% secondary, and 38.3

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. In this open-label, phase 3 study, after a lead -in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×10 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized

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. Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors. This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents

for the present dossier assessment. IQWiG employees involved in the dossier assessment:  Gregor Moritz  Lars Beckmann  Judith Gibbert  Thomas Kaiser  Florina Kerekes  Ulrike Lampert  Katrin Nink  Corinna ten Thoren Keywords: nonacog beta pegol, hemophilia B, benefit assessment Extract of dossier assessment A17-57 Version 1.0 Nonacog beta pegol (haemophilia B) 26 January 2018 Institute benefit assessment of new drugs. Biom J 2015; 58(1): 43-58 3. Collins PW, Young G, Knobe K, Karim FA, Angchaisuksiri P, Banner C et al. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood 2014; 124(26): 3880-3886. 4. Novo Nordisk A/S. Safety and efficacy of NNC-0156-0000-0009 in haemophilia B patients (paradigm 2): full text view [online