factor VII

FRONTIER2 data presented at ISTH 2024 showed that up to 95% of people, who had no prior prophylaxis treatment, experienced zero treated bleeds while on Mim8 BAGSVAERD, Denmark I June 23, 2024 I Novo Nordisk announced results from the phase 3 FRONTIER2 trial of 254 adults and adolescents aged 12 years and over with haemophilia A, with and without inhibitors. The trial assessed both once-weekly and once-monthly prophylactic treatment (regular treatment to prevent prolonged and spontaneous bleeding) with the investigational treatment Mim8. The data were presented at the International Society of Thrombosis and Haemostasis Annual Congress (ISTH 2024) in Bangkok, Thailand. In the trial population with no prior prophylaxis treatment: In the trial population with prior coagulation factor prophylaxis: “Despite treatment advances, there are still many unmet needs for people living with haemophilia A,” said FRONTIER2 lead investigator Dr Maria Elisa Mancuso, Senior Consultant in Haematology, Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital, Milan, Italy. “The FRONTIER2 data demonstrated superiority of Mim8 prophylaxis over both on demand treatment and prior clotting factor prophylaxis with respect to the number of treated bleeding episodes in people living with haemophilia A, regardless of their inhibitor status. It is also encouraging to see that in some subgroups in the study, up to 95% of people treated with Mim8 experienced zero bleeds.” Mim8 is a next-generation Factor VIIIa (FVIIIa) mimetic bispecific antibody designed with the potential to deliver sustained haemostasis. It is currently in development for once-weekly or once-monthly prophylaxis treatment for people living with haemophilia A, with and without inhibitors. Administered subcutaneously, Mim8 bridges Factor IXa/X (FIXa/FX), thereby replacing missing FVIII. This restores the body’s thrombin generation capacity, helping blood to clot. 1 In this trial, Mim8 was well-tolerated, and no safety concerns (thromboembolic events or related serious adverse events) were observed, in line with previous findings. “The FRONTIER2 efficacy and safety data is very encouraging,” said Martin Holst Lange, Executive Vice President of Development at Novo Nordisk. “With Mim8, we have the potential of offering a substantial proportion of patients the prospect of zero bleeds and convenient dosing flexibility to fit their lifestyles and needs. We look forward to discussing these data with regulatory authorities.” Contingent on regulatory interactions, Novo Nordisk aims to submit Mim8 for the first regulatory approval towards the end of 2024. Data from the ongoing phase 3 FRONTIER programme will continue to be disclosed at upcoming congresses and in publications in 2024 and 2025. About Haemophilia Haemophilia is a rare inherited bleeding disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding. It is estimated to affect approximately 1,125,000 people worldwide, and haemophilia A is estimated to account for 80-85% of all haemophilia cases. 2 Due to the nature of haemophilia being a rare x-linked recessive disorder, it often presents differently in males compared to females, with ~ 88% of people diagnosed with haemophilia worldwide being male. 3,4 There are different types of haemophilia, which are characterised by the type of clotting factor protein that is defective or missing. Haemophilia A is caused by a missing or defective clotting Factor VIII (FVIII). Some people with haemophilia may also develop inhibitors, which are an immune system response to the clotting factors in replacement therapy that cause treatment to stop working. Currently, it is estimated that up to 30% of people living with severe haemophilia A have inhibitors. 5 About the FRONTIER2 clinical trial The FRONTIER phase 3 clinical development programme investigates Mim8 as a prophylactic treatment for people with haemophilia A, with or without inhibitors. The phase 3 programme includes FRONTIER2 6 , FRONTIER3 7 , FRONTIER4 8 , and FRONTIER5 9 . FRONTIER2 is a 52-week efficacy and safety phase 3 trial, comparing once-weekly and once-monthly Mim8 versus no prophylaxis and versus prior coagulation factor prophylaxis (26-52-week run-in period) in people aged 12 years and over with haemophilia A, with or without inhibitors. The 26-week main phase of the trial is completed, a 26-week extension phase is ongoing. Participants were randomised into five treatment arms: Those who had received on-demand treatment prior to trial enrolment: Those who had received prophylaxis treatment prior to trial enrolment: About Novo Nordisk Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 66,000 people in 80 countries and markets its products in around 170 countries. Novo Nordisk’s B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com , Facebook , Instagram , X , LinkedIn and YouTube . References 1 Østergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice. Blood. 2021;138(14):1258-1268. doi:10.1182/blood.2020010331 2 Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, Germini F; Data and Demographics Committee of the World Federation of Hemophilia. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019 Oct 15;171(8):540-546. doi: 10.7326/M19-1208. 3 Centers for Disease Control and Prevention. What is Hemophilia? Available at: https://www.cdc.gov/ncbddd/hemophilia/facts.html Accessed: June 2024 4 Statista. Distribution of people with bleeding disorders worldwide in 2020, by gender. Available at: https://www.statista.com/statistics/495675/percentager-of-people-with-bleeding-disorders-in-worldwide-bygender/#:~:text=This%20statistic%20displays%20the%20percentage,with%20hemophilia%20A%20were%20males Accessed: June 2024 5 Kim JY, You CW. The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with hemophilia A. Blood Res. 2019 Sep;54(3):204-209. doi: 10.5045/br.2019.54.3.204. 6 ClinicalTrials.gov. A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors. Available at: https://clinicaltrials.gov/study/NCT05053139 Last accessed: June 2024. 7 ClinicalTrials.gov. A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors. Available at: https://clinicaltrials.gov/study/NCT05306418 Last accessed: June 2024. 8 ClinicalTrials.gov. A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4) (FRONTIER4). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05685238?term=NCT05685238&rank=1 Last accessed: June 2024. 9 ClinicalTrials.gov. A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5) (FRONTIER 5). Available at: https://clinicaltrials.gov/study/NCT05878938#xd_co_f=ZDM2YmY4ZmMtMmRhNi00YTI1LWI4YmItNTBjOWE4Yjg4NGI1~ Last accessed: June 2024. SOURCE: Novo Nordisk

HMB-001 was well tolerated with no drug-related adverse or thromboembolic events; dose-dependent improvements in blood-clotting activity support the potential of HMB-001 as a first-in-class prophylactic treatment for Glanzmann Thrombasthenia and other blood clotting disorders Preclinical HMB-001 findings were published in the February 2024 issue of Nature Cardiovascular Research COPENHAGEN, Denmark and CAMBRIDGE, Mass., Feb. 9, 2024 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, today presented initial results from Phase 1 of its ongoing evaluation of HMB-001. A novel bispecific antibody, HMB-001 is in development as a prophylactic treatment for the bleeding disorder Glanzmann Thrombasthenia (Glanzmann). The data were presented as one of 10 abstracts selected for the SLAM oral presentation session at the 17th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held this week in Frankfurt, Germany. "The first clinical data for HMB-001 in Glanzmann suggest that the demonstrated mechanism is suitable as a new prophylactic treatment for people with neglected blood clotting disorders who face severe, potentially life-threatening bleeds every day," said Joe Vogel, Senior Director and Program Lead for HMB-001 at Hemab. "With Phase 2 already underway, we are committed to advancing clinical evaluation of HMB-001 toward bringing life-changing preventative treatments to improve patients' quality of life." The Phase 1/2 first-in-human open-label study in patients with Glanzmann is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of HMB-001. As part of the UK-based Phase 1 single-ascending dose, seven patients received subcutaneous HMB-001 at 0.2 mg/kg, (n=1), 0.5 mg/kg (n=3) or 1.25 mg/kg (n=3). Over a 56-day observation period, HMB-001 was well tolerated; the most common adverse events (AEs) were mild or moderate in severity. No AEs or serious adverse events were deemed related to HMB-001. There were no dose-limiting toxicities and no thromboembolic events reported. Treatment with HMB-001 resulted in a dose-dependent pharmacodynamic effect of endogenous Factor VIIa accumulation that was associated with decreases in prothrombin time and improvement in exploratory thrombin generation analyses. The pharmacokinetic profile and half-life of HMB-001 support dosing every two weeks or a less-frequent dosing regimen. "People living with bleeding disorders like Glanzmann face devastating bleed events and considerable psychosocial impacts—from severe pain and social stigmatization to depression and isolation—but have no approved preventative treatments to turn to," said Suthesh Sivapalaratnam, MD, PhD, Queen Mary University of London, Barts Health NHS Trust. "These Phase 1 data support further investigation into the promise of HMB-001 for patients and providers across the globe who are awaiting innovation to improve the standard of care." Hemab has begun dosing and is actively enrolling in Phase 2, the multiple-ascending dose of the study, which will be expanded to sites across Europe and the U.S. For more information, visit clinicaltrials.gov (NCT06211634). In addition, Hemab announced that preclinical research findings of HMB-001 are now available online as part of the February 2024 issue of Nature Cardiovascular Research. The study results demonstrate the ability of HMB-001 to accumulate and potentiate the activity of endogenous Factor VIIa selectively on activated platelets, providing a sustained and localized procoagulant activity that may support prophylactic treatment of Glanzmann or other bleeding disorders. Read the paper here. About Glanzmann Thrombasthenia Glanzmann Thrombasthenia (Glanzmann) is a rare and severe bleeding disorder associated with debilitating and sometimes life-threatening bleeding episodes. Initial findings from the international Glanzmann's 360 (GT360) natural history study—Hemab's research initiative in partnership with UK specialist research consultancy Haemnet—found that 87% of the 104 respondents reported experiencing at least one bleed in the previous week, with 37% of those bleeds requiring medical treatment. These bleeding episodes significantly impact the mental health and quality of life of people living with Glanzmann. Low mood, emotional problems, and social isolation were reported by participants (66%, 50%, and 44% respectively), and 80% reported that they missed school or work due to bruising or bleeding. To date, there are no effective prophylactic treatment options for Glanzmann. About HMB-001 HMB-001 is bispecific antibody that binds and stabilizes endogenous Factor VIIa with one antibody arm and binds to TLT-1 on activated platelets with the other arm. This allows for accumulation of endogenous Factor VIIa in the body, recruitment of Factor VIIa directly to the surface of the activated platelets where it is known to facilitate clotting, and avoidance of clotting activity in the absence of tissue damage. HMB-001 is designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia with the potential to treat other debilitating rare bleeding disorders. The U.S. Food and Drug Administration granted Fast Track Designation to HMB-001 for the treatment of Glanzmann. About Hemab Therapeutics Hemab is a clinical-stage biotech company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in Cambridge, MA and Copenhagen, Denmark, Hemab is progressing a pipeline of monoclonal and bispecific antibody-based therapeutics to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5™, targets the development of 5 assets by 2025 to deliver long-awaited innovation for patients with high unmet need blood-clotting disorders like Glanzmann Thrombasthenia, Factor VII Deficiency, Von Willebrand Disease, and others. Learn more at hemab.com. Follow us on LinkedIn and X (formerly known as Twitter). SOURCE Hemab Therapeutics

Octapharma is Committed to Supplying Hospitals and Medical Providers with New Prothrombin Complex Concentrate PARAMUS, N.J., Jan. 3, 2024 /PRNewswire/ -- Octapharma USA has announced Balfaxar® (prothrombin complex concentrate, human-lans; marketed in Europe and Canada as octaplex®) is now available. The new non-activated four factor prothrombin complex concentrate (4F-PCC), approved by the U.S. Food and Drug Administration (FDA) this summer, is indicated for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for urgent surgery or invasive procedures. Continue Reading Octapharma has the Balfaxar® production flexibility to ensure consistent supply for hospitals and medical providers. Post this Octapharma USA has announced Balfaxar® (prothrombin complex concentrate, human-lans; marketed in Europe and Canada as octaplex®) is now available. Balfaxar®, a lyophilized powder for reconstitution, will be provided with sterile water for injection and the new transfer device, nextaro®. "The availability of Balfaxar® brings a welcome new treatment option for medical providers around the country," said Josh Goldstein, MD, PhD, Professor of Emergency Medicine at Harvard Medical School and Massachusetts General Hospital. "More than 2.4 million U.S. patients are prescribed warfarin to prevent blood clots from forming in patients who are at high risk.1 Unfortunately, the main side effect of warfarin is an increased risk of bleeding, which can complicate urgent surgery or invasive procedures.2 Clinical research has demonstrated that Balfaxar® is extremely effective in restoring blood coagulation by replenishing the levels of clotting factors that are deficient in those patients on warfarin." Balfaxar® is a non-activated 4F-PCC containing vitamin K-dependent factors: Factor II (prothrombin), Factor VII, Factor IX and Factor X, as well as antithrombotic Proteins C and S. "We are excited to announce the availability of Balfaxar® and are committed to providing the medical community with a valuable life-saving therapy," said Octapharma USA President Flemming Nielsen. "Octapharma has the production flexibility to ensure consistent supply for hospitals and medical providers now and in the future. We look forward to working with our critical care medicine partners to ensure patients receive the absolute best treatments available." The FDA approval of Balfaxar® was supported by the clinical trial LEX-209 (ClinicalTrials.gov Identifier: NCT02740335), which compared the efficacy and safety of Balfaxar® head-to-head with a control 4F-PCC (Kcentra®). The Phase III, randomized, double-blind, multicenter study randomized 208 patients to Balfaxar® (N=105) or control 4F-PCC (N=103). Balfaxar® met the primary endpoint of hemostatic efficacy in patients on a vitamin K antagonist undergoing urgent surgery with significant bleeding risk. The primary objective was met at the prespecified interim analysis and the study was stopped due to statistically significant efficacy results. Balfaxar® demonstrated effective hemostasis in 94.6% of patients versus 93.5% of patients for Kcentra®. International Normalized Ratio (INR) reductions and vitamin K dependent coagulation factor increases supported the primary endpoint and PCC dosing and duration of infusion were also similar. The safety profile was similar between treatment arms and consistent with previous studies.3 To study Balfaxar® further in other clinical scenarios, Octapharma is recruiting for two additional Phase III studies: LEX-210: Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor (ClinicalTrials.gov Identifier: NCT04867837) LEX-211: Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (ClinicalTrials.gov Identifier: NCT05523297) For more information on LEX-210 and LEX-211, please visit ClinicalTrials.gov. Kcentra® is a registered trademark of CSL Behring GmbH. For more information on Balfaxar®, please contact Octapharma customer service at 201-604-1130. About Balfaxar® Balfaxar® (prothrombin complex concentrate, human-lans) is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for an urgent surgery/invasive procedure. WARNING: ARTERIAL and VENOUS THROMBOEMBOLIC COMPLICATIONS Patients being treated with Vitamin K antagonists (VKA) therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events, especially in patients with the history of a thromboembolic event. Resumption of anticoagulation should be carefully considered as soon as the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Balfaxar® in clinical trials and post marketing surveillance. Monitor patients receiving Balfaxar® for signs and symptoms of thromboembolic events. Balfaxar® may not be suitable in patients with thromboembolic events in the prior 3 months. For complete boxed warning and full prescribing information, please visit Balfaxar.com/pi. About the Octapharma Group Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein manufacturers in the world, developing and producing human proteins from human plasma and human cell lines. Octapharma employs more than 11,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Hematology, Immunotherapy and Critical Care. Octapharma has seven R&D sites and five state-of-the-art manufacturing facilities in Austria, France, Germany and Sweden, and operates more than 190 plasma donation centers across Europe and the US. The company's American subsidiary, Octapharma USA, is located in Paramus, N.J. For more information, please visit octapharmausa.com. REFERENCES 1 - ClinCalc.com, Warfarin: Drug Usage Statistics, United States, 2013 - 2020, accessed June 19, 2023. 2 - Mayo Clinic, Warfarin side effects: Watch for interactions, accessed June 19, 2023. 3 - Ravi Sarode, Joshua N. Goldstein, Gregory Simonian, Truman J. Milling Jr; A Phase 3, Prospective, Randomized, Double-Blind, Multicenter, Non-Inferiority Study Comparing Two Four-Factor Prothrombin Complex Concentrates for Reversal of Vitamin K Antagonist-Induced Anticoagulation in Patients Needing Urgent Surgery with Significant Bleeding Risk. Blood 2022; 140 (Supplement 1): 352–353. doi: SOURCE Octapharma