January 15, 2018
Acceleron Pharma announced positive preliminary results for the first two cohorts in Part 1 of the Phase II clinical trial with ACE-083 in patients with facioscapulohumeral dystrophy (FSHD), a rare genetic muscle disorder that results in progressive focal muscle loss and weakness. The company plans to initiate Part 2 of the ACE-083 FSHD Phase II trial during the second quarter of 2018. Part 1 is an open-label, dose-escalation study of ACE-083 designed to evaluate safety as well as changes in total muscle volume in up to 36 patients with FSHD. Preliminary results include data from 23 patients evaluable for magnetic resonance imaging (MRI) among two different cohorts (11 patients with tibialis anterior weakness and 12 patients with biceps brachii weakness). Each patient received ACE-083 (150mg or 200mg) as a unilateral intramuscular injection once every three weeks for 12 weeks. Total muscle volume changes were measured by MRI relative to baseline at three weeks after the last injection of ACE-083. Based on overlap in dosing on a milligram per gram muscle analysis, dose cohorts were pooled for the analyses of each muscle. Strength and function tests are being explored in Part 1 to assist with the design of the randomized, double-blind, placebo-controlled Part 2 of the study.
BerGenBio Meets First Efficacy Endpoint in Phase II Trial
BerGenBio reported that the first efficacy endpoint has been met in its Phase II clinical trial evaluating BGB324 (bemcentinib) in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) who have progressed on an approved EGFR inhibitor (ClinicalTrials.gov Identifier: NCT02424617). The trial (known as BGBC004) is designed to test the hypothesis that selective AXL inhibition with the once-daily oral small molecule bemcentinib may reverse and prevent resistance to erlotinib, a therapy targeting constitutively active epidermal growth factor receptor (EGFR) signaling — a pathway frequently upregulated in cancers, particularly NSCLC. The trial is enrolling patients with activating EGFR mutations across three settings. Arm A is designed to determine the daily dose of bemcentinib that can be safely administered in combination with erlotinib in patients who have received prior erlotinib therapy. Arm B follows a Simon-like two-stage design evaluating the ability of bemcentinib to restore sensitivity to EGFR targeted therapy when given in combination with erlotinib in patients who have progressed on prior therapy with an approved EGFR inhibitor and that are negative for the T790M mutation. An overall disease control rate of 33 percent was reported in patients who completed at least one cycle of treatment (n=9) thus providing preliminary proof of concept that bemcentinib can restore sensitivity to EGFR targeted therapy in some patients. Arm C is designed to evaluate the ability of bemcentinib to prevent acquired resistance to EGFR targeted therapy when given in combination with erlotinib first line. This arm is recruiting patients with interim results expected mid-2018.
Positive Results From a Analysis of Delcath PHP Therapy
Delcath Systems issued results of a multicenter retrospective analysis of Delcath’s PHP Therapy. The study was conducted by researchers from Moffitt Cancer Center (Moffitt) in Tampa, FL, and the University Hospital Southampton (UHS) in the United Kingdom. Patients in the study were treated at the two centers between December 2008 and October 2016. Patients received up to four PHP treatments at UHS and up to six PHP treatments at Moffitt. All patients received at least one PHP treatment, the median number of treatments per patient was two and a total of 134 PHP treatments had been administered. Results showed that of the 51 treated patients, 22 (43.1 percent) showed a partial response, three (5.9 percent) showed a complete response and 17 (33.3 percent) had stable disease. The six-month overall and hepatic disease control rates were 64.7 percent and 70.6 percent, respectively. Survival analysis showed median overall survival of 15.3 months at the time of data cut off. One year overall survival was 64.6 percent. Safety analysis showed that 19 patients (37.5 percent) had Grade three or four non-hematologic toxicity. Cardiovascular toxicity was seen in 17.6 percent of patients, a rate comparable to the company’s prior Phase III study. The system has not been approved by the FDA, and is undergoing Phase III clinical testing in the U.S. as an investigational product.
Alder Announces Eptinezumab Meets Primary and All Key Secondary Endpoints
Alder BioPharmaceuticals announced that eptinezumab, its lead investigational product candidate for migraine prevention targeting calcitonin gene-related peptide (CGRP), met the primary endpoint in its pivotal Phase III PROMISE 2 clinical trial with very high statistical significance vs. placebo (p<0.0001) for both dose levels tested in the trial following a single quarterly infusion. In addition, eptinezumab met all key secondary endpoints with very high statistical significance vs. placebo including prevention beginning Day One (p<0.0001) and 50 percent (p<0.0001) and 75 percent (p<0.0001) responder rates month one through month three. Furthermore, 15 percent of eptinezumab patients had no migraines (i.e., 100 percent response) for a full three months (p<0.0001 unadjusted). Safety and tolerability were similar to previously reported eptinezumab studies. The observed safety profile in this study, to date, is consistent with previously reported eptinezumab studies. Adverse event rates among eptinezumab-treated subjects were similar to placebo-treated subjects. Commonly reported adverse events for eptinezumab, occurring at an incidence of 2.0 percent or greater, were nasopharyngitis (common cold) (6.3 percent), upper respiratory infection (4.0 percent), nausea (3.4 percent) and urinary tract infection (3.1 percent), arthralgia (joint pain) (2.3 percent), dizziness (2.6 percent), anxiety (2.0 percent) and fatigue (2.0 percent). If approved by the FDA, eptinezumab will be the first-to-market migraine prevention infusion therapy, with 100 percent of the treatment dose available upon administration.