Nabriva Therapeutics announced positive topline results from its Lefamulin Evaluation Against Pneumonia (LEAP 2) clinical trial. In LEAP 2, lefamulin met the U.S. Food and Drug Administration (FDA) primary endpoint of non-inferiority (NI, 10.0 percent margin) compared to moxifloxacin for early clinical response (ECR)-assessed 72 to 120 hours following initiation of therapy in the intent to treat (ITT) patient population. Lefamulin also met the European Medicines Agency (EMA) primary endpoint for non-inferiority (NI, 10.0 percent margin) compared to moxifloxacin based on an investigator assessment of clinical response. LEAP 2 was a global, randomized, double-blind, double-dummy trial that compared the efficacy and safety of 600 mg of oral lefamulin twice a day for 5 days versus 400 mg of oral moxifloxacin once daily for 7 days in 738 patients (370 in the lefamulin arm and 368 in the moxifloxacin arm). The lefamulin arm enrolled 183 (49.5 percent), 145 (39.2 percent) and 40 (10.8 percent) patients with a Pneumonia Outcomes Research Team (PORT) class of 2, 3 and 4, respectively. The moxifloxacin arm enrolled 189 (51.4 percent), 133 (36.1 percent) and 42 (11.4 percent) patients with a PORT class of 2, 3 and 4, respectively.
Avenue Therapeutics announced that its first pivotal Phase III trial of IV tramadol achieved the primary endpoint of a statistically significant improvement in Sum of Pain Intensity Difference over 48 hours (SPID48) compared to placebo in patients with moderate to moderately severe postoperative pain following bunionectomy surgery. The trial met its key secondary endpoints and demonstrated a clear dose response. Avenue plans to initiate a second pivotal Phase III trial of IV tramadol in patients following abdominoplasty surgery in the third quarter of 2018. The Phase III, multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of IV tramadol in 409 patients following bunionectomy surgery. Patients were randomized in a 1:1:1 ratio to a postoperative regimen of 50 mg of IV tramadol, 25 mg of IV tramadol or placebo administered over 15 minutes at hours 0, 2, 4 and once every 4 hours thereafter, for up to 13 doses. Based on a previous pharmacokinetic study, the 50 mg dosing regimen produces a similar Cmax (peak serum concentration) and AUC (area under the curve) to those of 100 mg oral tramadol given every 6 hours at steady state and reaches such Cmax after the third dose at hour 4. The IV tramadol 50 mg treatment arm achieved the primary endpoint of statistically superior improvement in SPID48 (p=0.005) compared to placebo.
Bioverativ presented initial clinical data for BIVV001 (rFVIIIFc-VWF-XTEN), a novel and investigational von Willebrand factor (VWF)-independent factor VIII therapy for people with hemophilia A. Preliminary safety and pharmacokinetic data from the ongoing EXTEN-A Phase I/IIa study showed that a single low dose of BIVV001 extended the half-life of factor VIII to 37 hours with high factor activity levels, and was generally well tolerated. EXTEN-A is an ongoing Phase I/IIa, open-label, multicenter study to evaluate the safety and pharmacokinetic (PK) of BIVV001 in both a low-dose and high-dose cohort of subjects aged 18-65 years with severe hemophilia A. Four adult males from the low-dose cohort received a single dose of rFVIII (25 IU/kg) followed, after a washout period, by a single low dose of BIVV001 (25 IU/kg). Primary endpoints include occurrence of adverse events and development of inhibitors. Secondary endpoints related to pharmacokinetic parameters were also presented. A single, low dose of BIVV001 extended the half-life of factor VIII to 37 hours, a substantial increase over the 13 hours seen with rFVIIIAverage factor VIII activity for the four subjects was 13.0 percent at five days and 5.6 percent at seven days post infusion with a single low dose of BIVV001. BIVV001 was generally well tolerated, with no development of inhibitors.
Sesen Bio announced positive, three-month data from its ongoing Phase III VISTA Trial of Vicinium for the treatment of patients with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG). The efficacy data being reported are based on three-month follow-ups from 111 patients. The VISTA Trial is an open-label, multicenter, single-arm Phase III clinical trial evaluating the efficacy and tolerability of Vicinium in patients with high-grade non-muscle invasive bladder cancer (NMIBC) that is carcinoma in situ (CIS) and/or papillary who have been previously treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the trial is the complete response rate in patients with CIS with or without papillary disease. Patients in the trial receive locally administered Vicinium twice a week for six weeks, followed by once-weekly treatment for another six weeks, then treatment every other week for up to two years. Vicinium has been well-tolerated in the VISTA Trial. In treated patients across cohorts (n=129), the most commonly reported treatment-emergent adverse events were urinary tract infection (29 percent), dysuria (19 percent), hematuria (16 percent), pollakiuria (12 percent), diarrhea (10 percent), fatigue (10 percent), micronutrition urgency (9 percent), and nausea (8 percent).