April 11, 2016
Portola Pharmaceuticals has reported topline data from a phase III study evaluating betrixaban compared with standard-of-care anticoagulation with injectable enoxaparin for the prevention of venous thromboembolism (VTE), or blood clots, in acute medically ill patients. APEX was designed to assess the relative risk (RR) in the composite endpoint of ultrasound-detected (asymptomatic) proximal deep venous thrombosis (DVT), symptomatic DVT, non-fatal pulmonary embolism (PE) or VTE-related death in high-risk acute medically ill patients treated with oral betrixaban for 35 to 47 days versus standard-of-care preventive anticoagulation with injectable enoxaparin dosed for 10±4 days. APEX enrolled 7,513 patients at more than 450 clinical sites worldwide. Cohort 1 achieved a p value of 0.054, which did not meet the threshold. Cohort 2 and the overall study population achieved p values of 0.029 and 0.006, respectively. There was no statistical difference in major bleeding between the betrixaban and enoxaparin arms in any of these three patient groups. The number of fatal bleeds was balanced between the two arms, and the number of intracranial hemorrhages was numerically lower in the betrixaban arm. Positive net clinical benefit with betrixaban was observed. The company will submit an NDA later in 2016.
January 7, 2013
CSL Behring published results from a phase II trial of fibrinogen concentrate for the improvement of blood clotting after elective aortic replacement surgery. This prospective, randomized, double-blind, placebo-controlled, parallel-group, stratified clinical study enrolled 61 patients who were undergoing elective aortic replacement surgery with cardiopulmonary bypass. If clinically relevant bleeding occurred during surgery, subjects received either 1g fibrinogen concentrate diluted in 50mL sterile water, or an equivalent volume of 0.9% saline as placebo. Doses were determined from the maximum clot firmness (MCF) value of the FIBTEM test. Results showed patients who received fibrinogen concentrate required fewer allogeneic blood product transfusions than patients receiving placebo (a median of two units in the fibrinogen concentrate group compared with 13 units in the placebo [p<0.001]). In the fibrinogen concentrate group, 45% of patients avoided transfusion entirely, whereas all 32 placebo patients required transfusion (p<0.001).
July 19, 2010
Daiichi Sankyo reported positive results from a phase III trial of edoxaban for the prevention of venous thromboembolic events following surgery. This multicenter, double-blind, double dummy, randomized trial, STARS E-3 (Studying Thrombosis After Replacement Surgery), enrolled 716 subjects undergoing total knee replacement in Japan and Taiwan. The subjects received either 30 mg once-daily oral dose of edoxaban or subcutaneous injection of 20 mg enoxaparin (standard of care) twice-daily for 11 to 14 days. The primary endpoint was the incidence of symptomatic pulmonary embolism (PE) and symptomatic and asymptomatic deep vein thrombosis (DVT). DVT occurred in 7.4% of the edoxaban arm compared with 13.9% of the enoxaparin arm (relative risk reduction of 46.8 percent; p≡0.01). There were no PE events observed in either treatment group. There was no statistically significant difference in major and clinically relevant non-major bleeding (p=0.13). Both treatment arms were well tolerated.
June 14, 2010
PolyMedix issued positive results from a phase Ib trial evaluating PMX-60056 for reversing the anticoagulant activity of low molecule weight heparin (LMWH). This double-blind, crossover study enrolled six subjects at a single site in the United States. The subjects were randomized into two cohorts and given a subcutaneous injection of tinzaparin (Innohep), an FDA approved LMWH, followed five and eight hours later by a ten-minute intravenous infusion of PMX-60056 or placebo. With the crossover design, on the second treatment day, each subject received the alternate treatment. PMX-60056 neutralized the anticoagulant activity of LMWH tinzaparin and normalized blood clotting time. PMX-60056 was safely administered with no serious adverse events.
August 18, 2008
Nuvelo issued positive results from a phase Ib trial of NU172 as a potential short-acting anticoagulant during medical procedures. This single center study enrolled 24 healthy male subjects who were placed into four dosing cohorts. Each cohort received a 2 mg/kg bolus dose followed by escalating infusion doses of NU172 for four hours. In all four cohorts, NU172 produced dose-dependent increases in anticoagulation, measured by activated clotting time (ACT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The highest infusion dose rate tested, 6.0 mg/kg/hr, resulted in an average ACT per subject ranging from 373 to 414 seconds and an increase of approximately three times baseline. Average PT values per subject ranged from 56 to 92 seconds and had an increase of approximately five times baseline. Average aPTT values per subject ranged from 130 to 178 seconds and had an increase of approximately five times baseline. These measurements remained stable throughout the four-hour infusion. Once the infusion ended, the coagulation parameters showed a rapid return toward baseline. NU172 was well-tolerated with no serious adverse events. Based on the results, Nuvelo plans to commence phase II studies in the fourth quarter of 2008 or the first quarter of 2009.
September 24, 2007
OMRIX and Ethicon reported positive results from a clinical trial of Evithrom, a human plasma derived blood clotting protein. This randomized trial enrolled 305 subjects with mild or moderate bleeding during elective cardiovascular, neurological or general surgical procedures. It was designed to compare hemostasis at three-, six- and 10-minute intervals in subjects receiving plasma-derived human thrombin and thrombin derived from bovine sources. The primary endpoint, non-inferiority in hemostasis at 10 minutes, was reached by 97.4% of the subjects following treatment with human thrombin. The percentages of subjects achieving hemostasis at three and six minutes were also equivalent. In addition, there were no statistically significant differences in several other variables including adverse events, laboratory assessments, vital signs, blood loss and blood transfusions. Evithrom was recently approved by the FDA.
July 24, 2006
Trigen reported positive results of a phase II trial of TGN 255 for the prevention of clotting during hemodialysis, at the XLIII ERA-EDTA Congress in Glasgow, Scotland. Trial data indicated that the drug was well tolerated, higher doses were associated with decreases in extracorporeal circuit clotting, and dose dependent changes in coagulation parameters (ACT, aPTT, TT) were noted. This open-label multi-center trial enrolled 28 patients, who received various doses of the drug across up to 3 dialysis sessions.
March 20, 2006
Lilly and Sankyo announced positive results of a phase Ib trial of prasugrel, for the treatment of platelet aggregation, at the 2006 Scientific Sessions of the American College of Cardiology in Atlanta. Trial data indicated that the drug produced a greater-than 20% inhibition in platelet aggregation in more than 90% of subjects, compared to less than 50% of subjects receiving approved treatment with clopidogrel. Efficacy was also noted in patients with more reactive platelets at baseline, a patient population more resistant to currently approved therapies. This randomized, controlled study enrolled 81 patients with stable cardiovascular disease, who received one of two doses of prasugrel (40 mg or 60 mg) or an approved dose of clopidogrel (300 mg).
October 24, 2005
Lilly and Sankyo has reported results of three early- stage clinical trials of prasugrel (CS-747) for the inhibition of platelet aggregation. Trial data indicated that all subjects receiving the drug responded to treatment, while 22% of low-dose- induction subjects and 43% of high-dose-induction subjects receiving the approved drug clopidogrel (Plavix) failed to respond (p<0.001). Each trial was a single-center, two-way cross-over pharmacology study enrolled a combined 112 healthy volunteers, who received loading doses of 60 mg prasugrel or 300 mg of the approved drug clopidogrel, followed by induction of platelet aggregation with one of two dose concentrations of adenosine diphosphate (5 micromolar or 20 micromolar).
June 6, 2005
Inspire Pharmaceuticals has issued positive results of a phase I trial of INS50589 Antiplatelet, for the prevention of platelet aggregation during blood transfusion. Results from the study yielded a positive safety profile, with no serious adverse events reported. Pharmacokinetics were dose dependent and in keeping with preclinical models. Biological activity was also observed, with statistically significant decreases in platelet aggregation at all doses, and complete inactivation of aggregation at the three highest doses, within 15-30 minutes of administration. Platelet aggregation returned to normal following discontinuation of infusion. This single center study enrolled sequential cohorts of healthy volunteers: the first cohort of 12 subjects was treated in an open-label fashion, while the second cohort of 24 subjects was treated in a double-blind, placebo-controlled arm. Following these results, the company announced plans to conduct a pre-clinical proof-of-concept study in an animal model of cardiopulmonary bypass surgery in Q3 2005.
January 5, 2004
AstraZeneca reported results of its phase III, EXULT B trial comparing the anticoagulant, Exanta (ximelagatran), to warfarin for the prevention of venous thormboembolism (VTE) in subjects undergoing total knee replacement (TKR) surgery. Of evaluable subjects, 22.5% of subjects receiving Exanta experienced VTE or death, compared to 31.9% of subjects treated with dose-adjusted warfarin. There was no statistically significant difference between the two treatment groups in the incidence of bleeding events, pulmonary embolism or death. This phase III, randomized, double-blind, double-dummy, international trial involved 2,303 subjects who, for 7 – 12 days, were treated with either Exanta 36 mg twice daily or warfarin. Incidence of VTE was measured by mandatory bilateral venography or by objective means, if VTE was symptomatic. The EXULT B study followed a first phase III study, EXULT A, which compared Exanta to warfarin in reducing blood clots following TKR surgery.
Esperion Therapeutics reported positive results from a second phase I study investigating ETC-642 (RLT Peptide), a complex of a 22-amino acid peptide and phospholipids for the treatment of cardiovascular disease. Results demonstrated the drug was safe and well tolerated. Data showed evidence of asymptomatic elevations of liver function tests in a one subject at the highest dose level (30 mg/kg). The randomized, double-blind, placebo-controlled study enrolled 20 subjects with cardiovascular disease. The study was designed to determine the maximum tolerated dose for single intravenous infusions of ETC-642. Subjects received one of three dose levels (10, 20 or 30 mg/kg) of ETC-642 or placebo.
July 21, 2003
ZymoGenetics reported positive results from a phase I trial investigating recombinant human Factor XIII (rFactor XIII) for the treatment of bleeding complications associated with congenital and acquired Factor XIII deficiencies. Result indicated that the expected dose-response relationship predicted from animal studies was observed, with a rise in rFactor XIII levels to 191% of normal in the highest dose group. No serious adverse events were reported and the most common side effect observed was headache. The double blind, placebo controlled, single-dose escalation study was designed to evaluate the safety and pharmacokinetics of rFactor XIII in healthy volunteers. Subjects were given a single intravenous injection (2 U/kg to 50U/kg), and then monitored for 28 days.