Antithrombin III Deficiency

LACHEN, Switzerland, June 6, 2023 /PRNewswire/ -- Octapharma to present new clinical and scientific findings for wilate®, Nuwiq®, octaplex® and atenativ® at the upcoming ISTH 2023 Congress New data and clinical study developments will be presented in nine posters and during two Supported Symposia The most recent developments from Octapharma's Haematology and Critical Care portfolios will be presented at the 31st Congress of the International Society on Thrombosis and Haemostasis (ISTH) on June 24–28, 2023, in Montréal, Canada. The data will be featured in nine poster presentations and two Supported Symposia during this key international meeting. Octapharma is a proud Silver Supporter of the ISTH 2023 Congress. There will also be a promotional booth focusing on modern approaches to bleeding and coagulation management. People with inherited bleeding disorders, such as haemophilia A and von Willebrand disease, are at risk of recurrent and prolonged bleeds placing a heavy burden on patients' lives. In addition to the risk of potentially life-threatening bleeds, increased bleeding is associated with long-term consequences that severely impair patients' quality of life. Patients with a deficiency of the prothrombin complex of coagulation factors are also at increased risk of bleeding. Such deficiencies may be inherited but can also be acquired and may be induced by the use of vitamin K antagonists (VKA) for anticoagulation therapy. During urgent surgery, rapid correction of the deficiency is required and can be achieved through the use of four-factor prothrombin complex concentrates (4F-PCC). 4F-PCC can also be used to control major bleeding associated with the use of direct oral anticoagulant (DOAC) therapy in patients with factor Xa inhibitors. The presentations at ISTH 2023 reflect Octapharma's long-term commitment to improving patient care and addressing unmet clinical needs. "We are proud to showcase our new data and provide updates of studies from across Octapharma's haematology and critical care portfolios at ISTH 2023," said Olaf Walter, Board Member at Octapharma. "Despite advances in the field, people with bleeding and coagulation disorders still face considerable challenges surrounding bleed management. At Octapharma, we strive to address such challenges head-on with the goal to improve the day-to-day lives of patients." Poster Presentations The WIL-31 study investigated the efficacy and safety of prophylaxis with wilate® in patients with von Willebrand disease (VWD) of any gender with VWD type 1, type 2 (except 2N) or type 3. The results of the study show that wilate® prophylaxis is highly effective at reducing the number of bleeds in children and adults, and provides compelling evidence to support the use of regular prophylaxis in patients with severe VWD. Further data on the efficacy and safety of wilate® prophylaxis is being collected in the WIL-33 study in children under six years of age. The goals and design of this study will be presented. Prophylaxis is already the standard of care for people with haemophilia A. The results of an indirect comparison show that fewer patients experienced bleeds when receiving personalised prophylaxis with Nuwiq® rather than prophylaxis with a comparator factor VIII (FVIII) product. New data exploring differences in the binding of different recombinant FVIII products to platelets in vitro will be shared in a separate poster. Although haemophilia A mainly affects males, female carriers may also have reduced levels of FVIII and be at increased risk of bleeding, especially during traumatic events such as surgery. Data from a retrospective case series of female haemophilia A carriers who were prescribed Nuwiq® during surgery at the Bonn Haemophilia Centre will provide an insight into the effective treatment of females. MOTIVATE is an ongoing, international investigator-initiated study made possible through funding from Octapharma AG, evaluating the management of haemophilia A patients with inhibitors. The Coordinating investigators, Drs Carmen Escuriola Ettingshausen and Robert F. Sidonio Jr., will provide an update on the study status as a poster at the Congress. The LEX-210 study will evaluate the haemostatic efficacy of octaplex® in patients with acute major bleeding receiving factor Xa inhibitors. As anti-factor Xa (anti-Xa) activity levels will be measured in these patients, the correlation between heparin-calibrated and specific factor Xa inhibitor assays has been analysed and will be presented. The results from the first head-to-head, phase 3, randomised, controlled trial (LEX-209) comparing two 4F-PCCs in patients on VKA anticoagulation who need urgent surgery will be presented, with a focus on dosing and haemostatic efficacy results. The results show that octaplex® was non-inferior to control 4F-PCC for rapid vitamin K antagonist reversal in patients undergoing urgent surgeries with significant bleeding risk. The posters will be presented at the following times: Sunday June 25, 18:30–19:30 ET PB0163. Differential binding of recombinant FVIII products to platelets, and impact of FVIII on VWF expression and platelet contractility in vitro. Presenting author: Viola Vogel. PB0235. Phase 3 study of the efficacy, pharmacokinetics, immunogenicity and safety of von Willebrand factor/factor VIII concentrate in patients with severe von Willebrand disease under 6 years of age. Presenting author: Akshat Jain. PB0238. Prospective, phase III study of the efficacy, safety, and pharmacokinetics of a human antithrombin III concentrate in congenital antithrombin deficiency during surgery or childbirth. Presenting author: Craig Kessler. Monday June 26, 18:30–19:30 ET PB0840. Efficacy of prophylaxis with a plasma-derived von Willebrand factor/factor VIII concentrate in patients with von Willebrand disease: Subgroup analysis by age and VWD type. Presenting Author: Robert F. Sidonio Jr. PB0681. German experience with simoctocog alfa during surgery in female haemophilia A carriers. Presenting author: Natascha Marquart. PB0584. Using heparin-calibrated assays to assess anti-factor Xa activity of factor Xa inhibitors (FXaI): a literature correlation analysis. Presenting author: Ravindra Sarode. PB1032. Four-factor prothrombin complex concentrates for vitamin K antagonist reversal before urgent surgery: dosing and hemostatic efficacy in a double-blind randomized study. Presenting author: Ravindra Sarode. Tuesday June 27, 18:30–19:30 ET PB1261. Matching adjusted indirect comparisons between personalized prophylaxis with simoctocog alfa versus standard prophylaxis with turoctocog alfa in adults with severe haemophilia A. Presenting author: Fernando F. Corrales-Medina. PB1288. Immune tolerance induction (ITI) strategies in haemophilia A patients with inhibitors – data from the MOTIVATE study. Presenting author: Carmen Escuriola Ettingshausen. Wednesday June 28, 13:00–14:00 ET PO11. Impact of simoctocog alfa prophylaxis on bleeding and joint health in Spanish patients with severe haemophilia A. Presenting author: María Teresa Alvarez-Román. Supported Symposia New clinical and scientific data, as well as updates on ongoing and new studies, will be shared during two Supported Symposia during the Congress. Final Results of the WIL-31 Study – A New Treatment Standard for von Willebrand Disease Patients with Severe Bleeding? Monday June 26, 13:15–14:30 ET, Room 511 Chair: Alok Srivastava, Christian Medical College, Vellore, India The symposium will focus on new data regarding the use of wilate® prophylaxis in children and adults to improve the lives of people with VWD. Topics presented will include the importance of prophylaxis, including current guidelines on the management of VWD and how to identify patients who may benefit from prophylactic treatment. Key learnings from the WIL-31 VWD prophylaxis study will be shared and case presentations of select WIL-31 patient cases from across the globe will be discussed. Bringing Together Two Worlds – Scientific and Clinical Insights for All-Round Bleed Protection in Haemophilia A Tuesday June 27, 13:15–14:30 ET, Room 511 Chair: Davide Matino, McMaster University, Hamilton, Ontario, Canada Octapharma's symposium on haemophilia A this year is dedicated to both, scientists and clinicians. The speakers will present data from the NuPreviq trial and the matching adjusted indirect comparisons (MAIC) analyses of Nuwiq® vs extended half-life (EHL) products as well as introduce the PROVE study. Topics discussed during this symposium will also include the role of platelets in FVIII binding, impact of prophylaxis on microRNA expression (biomarkers of joint and bone health) and how to utilise the power of RNASeq to understand inhibitor development. Both symposia will be open to congress participants in Montréal and will be streamed live for participants not attending the Congress. The opportunity to ask questions will be available at both symposia. Larisa Belyanskaya, Head of IBU Haematology at Octapharma commented: "We are delighted to showcase new data from WIL-31, which supports the importance of prophylaxis in people with von Willebrand disease, and to discuss scientific and clinical questions that need to be address to advance the management of people with haemophilia A." About Octapharma 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 than11,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Immunotherapy, Haematology 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 centres across Europe and the US. Octapharma has 40 years of experience in patient care. About Nuwiq® Nuwiq® (simoctocog alfa) is a 4th generation recombinant factor VIII (rFVIII) protein, produced in a human cell line without chemical modification or fusion with any other protein[1]. It is cultured without additives of human or animal origin, is devoid of antigenic non-human protein epitopes and has a high affinity for von Willebrand factor[1]. Nuwiq® treatment has been assessed in nine[1-3] completed clinical trials which included 201 previously treated patients (190 individuals)[1] and 108 previously untreated patients[2] with severe haemophilia A. Nuwiq® is available in 250 IU, 500 IU, 1,000 IU, 1,500 IU, 2,000 IU, 2,500 IU, 3,000 IU and 4,000 IU presentations[4]. Nuwiq® is approved for use in the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital FVIII deficiency) across all age groups[4]. About wilate ® wilate® is a high-purity human von Willebrand factor/factor VIII (VWF/FVIII) concentrate, that undergoes two virus inactivation steps during its production[5]. No albumin is added as a stabiliser[5]. The purification processes result in a 1:1 ratio of VWF to FVIII that is similar to normal plasma[5]. wilate® contains a VWF triplet structure and content of large high molecular weight multimers similar to normal human plasma[5]. wilate® is exclusively derived from large pools of human plasma collected in approved plasma donation centres[6]. wilate® is available in 500 IU and 1,000 IU presentations. wilate® is indicated for the prevention and treatment of haemorrhage or surgical bleeding in von Willebrand disease (VWD), when desmopressin (DDAVP) alone is ineffective or contra-indicated, and for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency)[6]. About octaplex® octaplex® is a human four factor prothrombin complex concentrate (4F-PCC) containing Factors II, VII, IX and X, as well as inhibitor protein C and its cofactor protein S. octaplex® is indicated for the treatment of bleeding and perioperative prophylaxis of bleeding in acquired deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when rapid correction of the deficiency is required. It can also be used in the treatment of bleeding and perioperative prophylaxis in congenital deficiency of the vitamin K dependent coagulation factors II and X when purified specific coagulation factor product is not available. octaplex® is presented in vials containing 500 IU and 1000 IU of human prothrombin complex. The total protein content per vial is 260–820 mg (500 IU vial)/ 520–1640 mg (1000 IU vial). The specific activity of the product is ≥ 0.6 IU/mg proteins, expressed as factor IX activity. Do not store above 25°C, do not freeze. Store in the original package in order to protect from light. The product shelf life is three years.[7] About atenativ® atenativ® is a human antithrombin III concentrate (AT III), which is presented in vials containing 500 IU and 1000 IU of human antithrombin III as lyophilised powder for infusion. After reconstitution with 10 mL water for injection (WFI), the solution provides 50 IU/mL or 100 IU/mL of human antithrombin III. Store in the refrigerator (2-8 °C) Keep the vials in the outer carton in order to protect from light. The shelf life is three years. It has been indicated for treatment of patients with congenital and acquired antithrombin deficiency including prophylaxis for the prevention of deep vein thrombosis and thromboembolism in clinical risk situations (especially in surgery, pregnancy and childbirth), in combination with heparin, if indicated, as well as prevention of the progression of deep venous thrombosis and thromboembolism associated with heparin as indicated.[8] atenativ® is currently not registered in Canada. 1. Lissitchkov T et al. Ther Adv Hematol 2019; 10:2040620719858471. 2. Liesner RJ et al. Thromb Haemost 2021; 121:1400-8. 3. Octapharma AG; Data on file. 4. Nuwiq® Summary of Product Characteristics. 5. Stadler M et al. Biologicals 2006; 34:281-8. 6. wilate® Summary of Product Characteristics. 7. octaplex® Summary of Product Characteristics. 8. atenativ® Summary of Product Characteristics. Octapharma press releases are specifically for health specialist/medical media and are not for consumer press. Logo - SOURCE Octapharma AG

Funding enables completion of ongoing Phase 1/2 study of bispecific antibody HMB-001 in Glanzmann Thrombasthenia, initiation of pivotal studies, start and conclusion of Phase 1/2 study of HMB-VWF in von Willebrand Disease, as well as future pipeline evolution. COPENHAGEN, Denmark and BOSTON, Feb. 21, 2023 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, today announced the closing of an oversubscribed $135 million Series B financing. Access Biotechnology led the round, with participation from new investors Deep Track Capital, Avoro Ventures, Invus, Rock Springs Capital, and Maj Invest Equity, as well as all current investors Novo Holdings, RA Capital Management, and HealthCap. "Hemab is fundamentally reimagining the treatment paradigm for underserved bleeding and thrombotic disorders. This financing will allow us to progress our clinical programs for the first prophylactic treatments for Glanzmann Thrombasthenia and von Willebrand Disease, delivering functional cures for patients in need," said Benny Sorensen, MD, PhD, CEO & President of Hemab. "We're grateful for this robust syndicate of investors who support our approach of leveraging validated advanced technologies and deep insights into the biology of clotting to overcome decades of scientific stagnation." The financing will support Hemab's scientific and corporate growth plans through 2025, including completion of an ongoing Phase 1/2 clinical study of lead candidate HMB-001 in Glanzmann Thrombasthenia, initiation of pivotal studies, start and completion of Phase 1/2 clinical evaluation for HMB-VWF in von Willebrand disease, and future pipeline evolution in accordance with the company's Hemab 1-2-5™ strategic guidance—targeting development of 5 clinical assets by 2025. "Strong investor confidence—in this case, an upsized round and more than $200 million in demand—is a testament to the expertise of the Hemab team, their validated scientific approach, and the opportunity to bring long-overdue innovation to patients living with severe bleeding and thrombotic diseases," said John Maraganore, PhD, Chair of Hemab's Board of Directors. "As founding investor and the company's largest shareholder, we are excited to support Hemab in the next phase of its plan to build the ultimate clotting company, with a Nordic foundation and global footprint," said Jørgen Søberg Petersen, MD, PhD, MBA, Partner at Novo Holdings. Hemab also announced Dan Becker, MD, PhD, Managing Director at Access, and Uya Chuluunbaatar, PhD, Partner at Avoro Ventures, will also join as Directors. Christine Borowski, PhD, Vice President at Access, will join as a Board Observer. "We are thrilled to partner with Hemab's exceptional leadership to advance a pipeline of transformative new medicines for areas of high unmet need in hemostatic disorders," said Dr. Becker. About Hemab Therapeutics Hemab is a clinical-stage biotech company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in the US and 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 1-2-5TM, targets the development of 5 clinical assets by 2025 to deliver long-awaited innovation for patients with Factor VII Deficiency, Bernard Soulier Syndrome, Von Willebrand Disease, Hereditary Hemorrhagic Telangiectasia (or Osler-Weber-Rendu disease), Congenital Antithrombin III Deficiency, and other serious disorders. Learn more at hemab.com. About HMB-001 HMB-001 is bispecific antibody that binds and stabilizes endogenous factor VIIa (FVIIa) with one antibody arm and TLT-1 on activated platelets with the other arm. This allows for accumulation of FVIIa in the body, recruitment of FVIIa 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 was designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia with potential for other debilitating rare bleeding disorders. It entered Phase 1/2 clinical evaluation in late 2022, with initial data expected 2H 2023. SOURCE Hemab Therapeutics

LACHEN, Switzerland, Dec. 5, 2022 /PRNewswire/ -- New clinical data from Octapharma's haematology portfolio, including the results of the phase 3 WIL-31 study, will be presented during the Scientific Program at the 64th American Society of Hematology (ASH) Meeting on December 10–13, 2022. Prophylaxis with wilate® significantly reduced bleeding rates in children and adults with any type of von Willebrand disease (VWD) in the phase 3 WIL-31 study. Significantly higher zero bleed rates were observed in haemophilia A patients undergoing pharmacokinetic-personalised prophylaxis with Nuwiq® versus comparator products based on matching-adjusted indirect comparison (MAIC) analyses. The NuPOWER study will investigate the efficacy and safety of Nuwiq® for the management of bleeding during major surgery in patients with haemophilia A on emicizumab prophylaxis. The ATN-06 study will investigate the efficacy, safety and single-dose pharmacokinetics of Atenativ® in patients with congenital antithrombin deficiency undergoing surgery or childbirth. Olaf Walter, Board Member and Head of International Business Units at Octapharma, stated, "We look forward to highlighting our continued efforts in improving the care for people with bleeding disorders." Larisa Belyanskaya, Head of IBU Haematology, added: "The positive results of the WIL-31 study support the use of regular wilate® prophylaxis in people with von Willebrand disease of all ages and all types. The MAIC analysis strengthens the use of personalised prophylaxis with Nuwiq® for bleed management in patients with haemophilia A. The NuPOWER study will give important insight into the use of FVIII in haemophilia A patients on emicizumab during surgery, while the ATN-06 study will provide insights into the prevention of thrombosis in people with congenital antithrombin deficiency during surgery." Aiming for all-round bleed protection in people with haemophilia A and von Willebrand disease and prevention of thrombosis in people with congenital antithrombin deficiency: The phase 3 WIL-31 study investigated the efficacy and safety of wilate® prophylaxis over 12 months in people of all ages with VWD of any type. The primary endpoint was achieved, with an 84% reduction in annualized bleeding rate (ABR) compared with on-demand treatment during the prior run-in study. The median spontaneous ABR decreased by 95%. No serious drug-related adverse events or thrombotic events occurred during prophylaxis with wilate®. The findings indicate that prophylaxis with wilate® is effective in children and adults with VWD of all types. In rare diseases, such as haemophilia A, it is difficult to perform head-to-head studies directly comparing different products. Instead, indirect comparison methods, such as MAIC, can be used to assess the relative treatment effects of different products across studies. A series of MAIC analyses was performed comparing the efficacy of pharmacokinetic-guided, personalised prophylaxis with Nuwiq® with that of personalised prophylaxis regimens with three other FVIII products. The results showed that personalised prophylaxis with Nuwiq® can lead to decreased ABRs and significantly higher rates of patients with zero bleeds compared with comparator products. People with haemophilia A who are receiving emicizumab prophylaxis and need to undergo surgery often require additional haemostatic therapy to control bleeding during and after the invasive procedure. However, there are limited data on the safety and efficacy of using emicizumab and concomitant therapy during surgery. The NuPOWER study will therefore investigate the perioperative efficacy and safety of Nuwiq® in patients receiving emicizumab prophylaxis who undergo major surgery. The study is planned to start in 2023. People with congenital antithrombin deficiency have an increased risk for thrombosis, particularly during high-risk periods such as surgery or childbirth. Anticoagulation therapy (e.g., with an antithrombin concentrate) is therefore advisable in such settings. The ATN-06 study is investigating the use of Atenativ® in people with congenital antithrombin deficiency undergoing surgery or childbirth. Site initiation has begun in 8 countries and 15 sites, and patient enrolment has started. "We are excited to provide updates to the bleeding disorder community at the 64th ASH Meeting," continued Olaf Walter, "The ASH Meeting is an important platform to further demonstrate Octapharma's constant commitment to reducing the burden of living with a bleeding disorder and improving patients' lives". About haemophilia A and VWD Haemophilia A is an X-linked hereditary bleeding disorder caused by a deficiency of factor VIII (FVIII) which, if left untreated, may lead to haemorrhages in muscles and joints and consequently to arthropathy and severe morbidity. The disorder affects around one in every 10,000 males worldwide. Prophylaxis with replacement FVIII therapy reduces the number of bleeding episodes and the risk of permanent joint damage. VWD is the most common inheritable bleeding disorder caused by deficient or defective clotting protein von Willebrand factor (VWF). Currently, recommended guidelines on the use of prophylaxis are limited. VWD affects males and females equally but is diagnosed more frequently in women due to heavy menstrual bleeding and childbirth. Guidelines for managing these issues are also inadequate. About Octapharma 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 around 10,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Immunotherapy, Haematology, 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 180 plasma donation centres across Europe and the US. About Nuwiq® Nuwiq® (simoctocog alfa) is a 4th generation recombinant factor VIII (rFVIII) protein, produced in a human cell line without chemical modification or fusion with any other protein1. It is cultured without additives of human or animal origin, is devoid of antigenic non-human protein epitopes and has a high affinity for von Willebrand factor2. Nuwiq® treatment has been assessed in nine2-4 completed clinical trials which included 201 previously treated patients (190 individuals)2 and 108 previously untreated patients3 with severe haemophilia A. Nuwiq® is available in 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 2500 IU, 3000 IU and 4000 IU presentations5. Nuwiq® is approved for use in the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital FVIII deficiency) across all age groups5. About wilate® wilate® is a high-purity human VWF/FVIII concentrate, that undergoes two virus inactivation steps during its production6. No albumin is added as a stabiliser6. The purification processes result in a 1:1 ratio of VWF to FVIII that is similar to normal plasma6. wilate® contains a VWF triplet structure and content of large high molecular weight multimers like normal human plasma6. wilate® is exclusively derived from large pools of human plasma collected in approved plasma donation centres6. wilate® is available in 500 IU and 1000 IU presentations. wilate® is indicated for the prevention and treatment of haemorrhage or surgical bleeding in VWD, when desmopressin (DDAVP) alone is ineffective or contra-indicated, and for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital FVIII deficiency)6. Octapharma press releases are specifically for health specialist/medical media and are not for consumer press. References Lissitchkov T et al. Ther Adv Hematol 2019; 10:2040620719858471. Liesner RJ et al. Thromb Haemost 2021; 121:1400-8. Octapharma AG, data on file. Nuwiq® Summary of Product Characteristics. Stadler M et al. Biologicals 2006; 34:281-8 wilate® Summary of Product Characteristics. Logo - SOURCE Octapharma AG