Date: 2015-12-07
Type of information: Presentation of results at a congress
phase: 2-3
Announcement: presentation of results at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando
Company: Baxalta (USA - IL)
Product: Adynovate® - BAX 855
Action
mechanism: blood coagulation factor/protein. Adynovate®/BAX 855 is based on Advate®, a full-length FVIII molecule. Through a collaboration with Nektar Therapeutics, BAX 855 leverages proprietary PEGylation technology designed to extend the duration of activity of proteins in the body. The drug has been developed through a collaboration with Nektar Therapeutics.
Disease: hemophilia A
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
Country: Australia, Austria, Bulgaria, Czech Republic, Germany, Israel, Japan, Republic of Korea, Lithuania, Malaysia, Netherlands, Poland, Romania, Spain, Sweden, Switzerland, Taiwan, Ukraine, UK, USA
Trial
details: The first study has been designed to assess efficacy and safety, including immunogenicity of BAX 855 administered as prophylaxis and as on-demand therapy in adult and adolescent (12-65 years) previously treated patients (PTPs) with severe hemophilia A To determine the pharmacokinetic (PK) parameters of BAX 855. The second study is a phase 1 prospective open-label, dose-escalation study. The objectives of this study are to assess the tolerability and safety after single dose treatments of BAX 855 in previously treated patients (PTPs) with severe hemophilia A, to determine the pharmacokinetic (PK) parameters of BAX 855 compared in crossover with ADVATE, and to evaluate the impact of anti-polyethylene glycol (PEG) antibodies on PK parameters. (NCT01736475 and NCT01599819)
Latest
news: * On December 7, 2015, Baxalta presented data on the clinical experience with newly-approved hemophilia A treatment Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] at the 57th American Society of Hematology (ASH) Annual Meeting. Further analyses of the data from the Adynovate® pivotal trial investigated characteristics of patients who achieved zero bleeds in the study. In the pivotal trial, 40 of the 101 patients (39.6 percent) achieved zero bleeding during six months of prophylactic treatment with Adynovate®. While some characteristics were similar across all participants, patients without bleeding generally had fewer target joints at screening, lower median historical annualized bleeding rates, and lower incidence of blood type O. (Characteristics of Patients without Bleeding in a Pivotal Trial of Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855) in the Treatment of Hemophilia A. Pub # 1105). Additional post-hoc sub analysis from the pivotal trial addressed joint bleeding patterns among patients receiving twice-weekly prophylaxis treatment with Adynovate®. Approximately two-thirds of previously-treated patients (PTPs) in the study (69 of 101 PTPs, 68.3 percent) receiving Adynovate® had at least one “target joint” when they entered the study (ankle, knee, hip, or elbow with three or more spontaneous bleeding episodes in any consecutive 6-month period). The analysis found that Adynovate® was efficacious in treating breakthrough bleeds and reducing overall annualized joint bleeding rates among patients with “target joints”. (Joint Bleeding Patterns in Patients Treated Prophylactically with an Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855). Pub # 2300) Baxalta has also conducted a Phase 3 study evaluating the efficacy and safety of Adynovate® for the perioperative control of hemostasis among 15 patients with severe hemophilia A undergoing surgical procedures. An interim analysis indicates that Adynovate® can support effective hemostatic control in this patient population for the intraoperative (during the procedure), postoperative (24 hours after completion of the procedure), and perioperative (from start of the procedure until discharge or day 14) periods. (Perioperative Efficacy of an Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855) in Individual Procedures. Pub # 2299. In November 2015, the company initiated a study of previously-untreated patients (PUPs) and minimally-treated patients (MTPs) with severe hemophilia A. This global, Phase 3 study aims to enroll at least 100 patients between the ages six months and six years to evaluate the safety and hemostatic efficacy of Adynovate® in this population. In parallel, a Phase 3, prospective, randomized, multi-center study has been initiated to evaluate additional dosing regimens with Adynovate®, using pharmacokinetic (PK)-guided prophylaxis among approximately 100 adults with severe hemophilia A (the PROPEL study). The study is designed to compare outcomes of PK-guided treatment with Adynovate® targeting FVIII trough levels of 1-3 percent vs. approximately 10 percent (8-12 percent). Baxalta is advancing this research in an effort to help more patients achieve zero bleeds through higher trough levels. Please visit clinicaltrials.gov for more information on both studies. * On July 16, 2015, Baxalta, a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, announced the publication of the complete data from the Phase II/III pivotal study and Phase I trial of BAX 855 in Blood, the journal of the American Society of Hematology. Following on initial presentations of the data in 2014, the publication provides a comprehensive overview of the clinical trial results of BAX 855, which will be marketed in the United States under the brand name ADYNOVATE [Antihemophilic Factor (Recombinant), Pegylated] upon approval. The trial assessed the treatment’s safety and efficacy profiles for bleed prevention with a twice-weekly dosing schedule, showing a mean half-life extension of 1.4- to 1.5-fold compared with ADVATE. The positive study results were originally reported in August of 2014 and supported the company’s December 2014 submission for approval of BAX 855 to the FDA. The prospective, global, multi-center, open-label, two-arm Phase II/III study evaluated BAX 855 among 137 previously treated patients (PTP) with hemophilia A who were aged 12 to 65. Patients were assigned to either twice weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-60 IU/kg, n=17). As previously disclosed, BAX 855 met the study\'s primary endpoint for the prevention of bleeding episodes and the treatment with prophylaxis compared to on-demand treatment. Patients in the twice- weekly prophylaxis arm of the trial experienced a 95 percent reduction in median annualized bleed rate (ABR) as compared with those in the on-demand arm (1.9 vs. 41.5, respectively). BAX 855 was also effective in treating all bleeding episodes, 95.9 percent of which were controlled with one or two infusions at a median dose of 29.0 IU/kg per infusion. Treatment was rated excellent or good for nearly all bleeding episodes (96.1 percent). In the prophylactic group (n=101), 39.6 percent of compliant patients experienced no bleeds. The study also showed that BAX 855 pharmacokinetics offered a 1.4 to 1.5- fold mean extended half-life compared with ADVATE with a median infusion interval of 3.6 days, supporting the findings from the Phase I trial. No patients developed inhibitors to BAX 855 and no treatment-related serious adverse events, including hypersensitivity reactions, were reported. Seven adverse reactions in six patients, including headache, diarrhea, nausea, and flushing were reported. Baxalta\'s Continuation Study is ongoing for patients who completed the pivotal trial and the pediatric Phase III study among previously treated patients under the age of 12 with severe hemophilia A. This continuation study is also available for patients who have not participated in previous BAX 855 studies. Upon completion of the pediatric study, Baxalta expects to file for marketing authorization with the European Medicines Agency in 2016.
