Octapharma USA Research Results Presented at HTRS Symposium Targeting Major Challenges Facing Hemophilia Patients04-20-2017
Global Clinical Trials Focus on Inhibitor Development, Dosing Frequency
HOBOKEN, N.J. (April 19, 2017) – Octapharma USA presented interim clinical research results at the Hemostasis and Thrombosis Research Society Scientific Symposium in Scottsdale, Arizona, updating the bleeding disorders community on the company’s studies investigating two major challenges facing Hemophilia patients – the development of inhibitors and the need for frequent venous access for Factor VIII (FVIII) injection.
The research team for Octapharma’s Phase 3, international study, GENA-05 (NuProtect), reported interim data on the rate of inhibitor development in previously untreated patients (PUPs) treated with Octapharma’s human cell line recombinant FVIII (Human-cl rhFVIII). Final data are expected in 2019.
Human-cl rhFVIII is marketed in the U.S. as NUWIQ®, Antihemophilic Factor (Recombinant) Lyophilized Powder for Solution for Intravenous Injection. NUWIQ® is a recombinant antihemophilic factor indicated in adults and children with Hemophilia A for on-demand treatment and control of bleeding episodes; perioperative management of bleeding; and routine prophylaxis to reduce the frequency of bleeding episodes.
“This research is vitally important because there still remain major unmet medical needs for Hemophilia A patients that can lead to significant morbidity,” said Octapharma USA President Flemming Nielsen. “One is the high incidence of inhibitor development, which reduces the efficacy and effectiveness of FVIII therapies, leading to more frequent bleeding episodes. Octapharma is committed to research and therapies that help advance patient care for the bleeding disorders community.”
Octapharma GENA-05 researchers analyzed data for 66 PUPs with ≥20 exposure days (EDs), the time when inhibitors are most likely to arise. Of 59 patients with available FVIII gene mutation analysis, 47 (81.0%) had null mutations, 44 (74.6%) had high-risk mutations, and 1 (1.7%) had no mutation identified. High-titre inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6–24). Five patients developed a low-titre inhibitor (4 were transient). Two patients developed an inhibitor (1 high-titre) after 20 EDs. The cumulative incidence was 12.8% for high-titre inhibitors (95% CI: 4.49–21.15), 8.4% for low-titre inhibitors (95% CI: 1.28–15.59) and 20.8% for all inhibitors (95% CI: 10.68–30.95). Twelve out of 13 inhibitor patients had identifiable FVIII gene mutation, all were null, and 12 were high-risk. The completed study aims to investigate primarily the immunogenicity and secondarily efficacy, safety and tolerability of NUWIQ® over 100 EDs, for a maximum period of five years from screening.
Octapharma is further investing in NUWIQ® for the benefit of patients with clinical studies of the dosing process (GENA-21 and GENA-21b) to investigate the frequency of dosing with personalized prophylaxis. In the GENA-21 (NuPreviq) study, adult Hemophilia A patients were originally started on infusions three times per week or every other day. Subsequent dosing intervals were then determined based on individual pharmacokinetic (PK) data, which resulted in a median dosing interval of 3.5 days and with 58% of patients on a twice a week or fewer infusion schedule.1
GENA-21b is an ongoing global, prospective, open-label, multicenter phase 3b study undertaken to confirm the data of GENA-21 and assess the benefit of PK-guided individualized prophylaxis in previously treated patients predominantly on routine prophylaxis. During HTRS, Octapharma researchers reported snapshot data for GENA-21b, regarding the investigation of PK-guided dosing that may result in longer recommended treatment intervals and lower FVIII consumption than during regular prophylaxis.
The median treatment interval during regular prophylaxis is 2.3 days, or three times per week. During individualized prophylaxis in the study, 58.6% of patients were recommended to receive treatment twice per week or less with a recommended median treatment interval of 3.5 days at an average single dose of 44 IU/Kg. The median annual bleed rate (ABR) for patients in this trial was 0. The data in the study to date suggest that patients may potentially experience a 21% reduction in overall FVIII usage through personalized prophylaxis compared to regular prophylaxis with NUWIQ®.2 Such results are preliminary and may change as more study data are collected.
Octapharma’s third research presentation at HTRS introduced WIL-27, a study to investigate the pharmacokinetics, efficacy, safety, and immunogenicity of WILATE® in previously treated patients with severe Hemophilia A. This prospective, international, multi-center Phase 3 study seeks 55 male participants at clinical trial sites in the U.S. and Europe.
Study participants must have severe hemophilia A and be age 12 or older. For more information, please contact Sylvia Werner, Octapharma USA Director of Clinical Operations, at (201) 604-1149 or sylvia.werner. The complete study protocol is available at @octapharma .comwww.ClinicalTrials.gov; ClinicalTrials.gov Identifier: NCT02954575.
NUWIQ® Important Safety Information
NUWIQ® is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product or its components. Hypersensitivity reactions, including anaphylaxis, are possible. Should symptoms occur, discontinue NUWIQ® and administer appropriate treatment. Development of Factor VIII neutralizing antibodies (inhibitors) may occur. If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures Factor VIII inhibitor concentration. Monitor all patients for Factor VIII activity and development of Factor VIII inhibitor antibodies. The most frequently occurring adverse reactions (0.7%) in clinical trials were paresthesia, headache, injection site inflammation, injection site pain, non-neutralizing anti-Factor VIII antibody formation, back pain, vertigo, and dry mouth. For full prescribing information on NUWIQ®, please visit www.nuwiqusa.com.
WILATE® Important Safety Information
WILATE® is indicated in children and adults with von Willebrand disease for on-demand treatment and control of bleeding episodes; and perioperative management of bleeding. WILATE® is contraindicated for patients who have known hypersensitivity reactions, including anaphylactic or severe systemic reaction, to human plasma-derived products, any ingredient in the formulation, or components of the container. Thromboembolic events have been reported in VWD patients receiving coagulation factor replacement therapies. FVIII activity should be monitored to avoid sustained excessive FVIII levels. Development of neutralizing antibodies to FVIII and to VWF, especially in VWD Type 3 patients, may occur. WILATE® is made from human plasma. The risk of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jacob disease agent, cannot be completely eliminated. The most common adverse reactions to treatment with WILATE® in patients with VWD were hypersensitivity reactions, urticaria, and dizziness. Seroconversions for antibodies to parvovirus B19 not accompanied by clinical signs of disease have been observed. The most serious adverse reactions to treatment with WILATE® in patients with VWD were hypersensitivity reactions. For full prescribing information on WILATE®, please visit www.wilateusa.com.
About the Octapharma Group
Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein products manufacturers in the world and has been committed to patient care and medical innovation since 1983. Its core business is the development and production of human proteins from human plasma and human cell lines. Octapharma employs approximately 7,100 people worldwide to support the treatment of patients in over 113 countries with products across the following therapeutic areas: Hematology (coagulation disorders), Immunotherapy (immune disorders) and Critical Care. The company’s American subsidiary, Octapharma USA, is located in Hoboken, N.J. Octapharma operates two state-of-the-art production sites licensed by the U.S. Food and Drug Administration (FDA), providing a high level of production flexibility. For more information, please visit www.octapharmausa.com.
1 – Octapharma, Data on file. 2015.
2 – Klamoth, R., et al. 2015. Personalized Prophylaxis with Human-cl rFVIII (NUWIQ®) in Hemophilia A Patients. International Symposia of Thrombosis and Hemostasis (ISTH). Toronto, Canada.
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