January 29, 2018
Array BioPharma announced updated results from the 30 patient safety lead-in of the Phase III BEACON CRC trial evaluating the triplet combination of encorafenib, in patients with BRAF-mutant metastatic colorectal cancer (CRC) whose disease has progressed after one or two prior regimens. The randomized, open-label, global trial enrolled 30 patients who were treated in the safety lead-in and received the triplet combination (encorafenib 300mg daily, binimetinib 45mg twice daily and cetuximab per label). The confirmed overall response rate (ORR) in patients with the BRAFV600E mutation was 48%, and three patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy. These data represent substantial improvements compared to several separate historical published standard of care benchmarks for this population. In the safety lead-in, the triplet combination was generally well-tolerated. The most common grade three or four AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30). All patients with elevated baseline levels of the tumor markers CEA and CA19-9 had a reduction from baseline, with similar and substantial (median 83% – 96%) reductions across both markers in patients with objective responses and those with stable disease. The enrollment in the randomized portion of the BEACON CRC trial is ongoing.
Zealand Pharma’s Glepaglutide hits primary efficay endpoint
Zealand Pharma announced Phase II key results for glepaglutide, a GLP-2 analog being developed for the treatment of short bowel syndrome (SBS). The trial was a three-week, proof-of-concept, double-blind, cross-over, dose-finding trial investigating the efficacy and safety of three different doses of glepaglutide (10mg, 1mg and 0.1mg per day). A total of 16 SBS patients completed the trial. Glepaglutide was observed to be safe and well-tolerated. The primary efficacy endpoint of reducing fecal wet weight output (ostomy output or diarrhea) was successfully met for both the 1mg and 10mg doses, with reductions of 592 g/day (p=0.002) and 833 g/day (p=0.0002), corresponding to a relative reduction of 23% and 30% for the mid and high dose groups, respectively. No effects were seen with the lowest dose. Key secondary endpoints were also met for the two high doses, including an absolute change in intestinal wet weight absorption of 645 g/day and 786 g/day and a relative increase in urine output of 40% and 32% for the mid and high doses, respectively. Based on results from a recently completed pharmacokinetic trial, both a once- and twice-weekly dosing regimen is proposed for Phase III and the trial is expected to enroll between 120 and 150 patients. Meetings with U.S. and EU regulatory authorities to agree on the final trial design are planned, with the aim of commencing Phase III clinical trials in 2018.
Amgen Reports Aimovig Met All Primary and Secondary Endpoints in Phase IIIb Study
Amgen reported positive results from the Phase IIIb LIBERTY study assessing the efficacy and safety of Aimovig (erenumab) 140mg in patients with episodic migraine who had experienced two to four previous preventive treatment failures, due to lack of efficacy or intolerable side effects. The multicenter, randomized 12-week, double-blind, placebo-controlled study enrolled 246 participants. The study includes an ongoing 52-week open-label extension study. The study met its primary endpoint, with significantly more patients taking Aimovig experiencing at least a 50 percent reduction from baseline in their monthly migraine days as compared to placebo. LIBERTY also met all secondary endpoints, including reduction of monthly migraine days, reduction in days needing acute (rescue) medication, improvement in scores on the Migraine Physical Function Impact Diary (MPFID) tool, and 75 percent and 100 percent responder rates (number of patients experiencing at least a 75 percent or 100 percent reduction in monthly migraine days compared to placebo). The safety data are consistent with previous studies of Aimovig to date. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018.