Bergenbio AS, of Bergen, Norway, reported data at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich showing that lead candidate BGB324, a selective Axl kinase inhibitor, can be safely administered to patients with advanced non-small-cell lung cancer (NSCLC) at doses that achieve durable disease control. BGB324 was administered at an oral loading dose (600 mg) on days one and two, followed by a daily maintenance dose (200 mg) to eight patients with previously treated advanced NSCLC. Two of the eight patients achieved stable disease for at least nine months. Treatment was well-tolerated with no patients discontinuing therapy as a result of toxicities. Exposure to BGB324 also was accompanied by increases in patient plasma levels of soluble AXL receptor. Bergenbio is now analyzing data from the Tarceva (erlotinib, Roche Holding AG) combination therapy arm of the study.
Biondvax Pharmaceuticals Ltd., of Ness Ziona, Israel, reported preliminary safety results from its European phase IIb trial of M-001, its universal flu vaccine candidate, with blinded data showing three moderate adverse events considered to be possibly or probably related to treatment and no severe adverse events. The trial is designed to compare safety and immunogenicity of M-001 between a control group receiving saline as a placebo and then the standard H5N1 avian pandemic vaccine, and an experimental group receiving Biondvax’s M-001 as a primer prior to receiving the same H5N1 pandemic vaccine.
Biovie Inc., of Beverly, Mass., said it submitted an IND to the FDA for BIV201, which is designed to target ascites due to chronic liver cirrhosis. Once cleared, Biovie plans to start a phase Ib trial of the orphan-designated drug in U.S. ascites patients in 2017.
Blueprint Medicines Corp., of Cambridge, Mass., reported data from its phase I trial testing BLU-554, a selective inhibitor of fibroblast growth factor receptor 4, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich. As of the data cutoff date of Nov. 7, 25 patients with hepatocellular carcinoma (HCC) had been treated in the dose-escalation portion of the trial at five dose levels (ranging from 140 mg once daily to 900 mg once daily), with the majority of patients having previously received Nexavar (sorafenib, Amgen Inc. and Bayer AG). The study was designed to retroactively assess patient biopsies for FGFR4 pathway activation after enrollment by evaluating levels of FGF19, the protein that activates FGFR4, using an investigational immunohistochemistry assay. Pharmacokinetic data across all dose levels showed rapid oral absorption, a mean half-life of about 10 hours and exposure in the expected therapeutic range based on HCC xenograft models. Pharmacodynamic data demonstrated FGFR4 pathway inhibition with BLU-554, as evidenced by effects on metabolic pathways downstream of FGFR4, with increases in the bile acid precursor C4, decreases in cholesterol and feedback up-regulation of the ligand FGF19 in blood. Of 25 patients evaluable for efficacy, one had a confirmed partial response (PR), 12 had stable disease (including seven who had tumor reductions but did not reach the PR threshold). Of 10 evaluable patients with FGF19 overexpression in their tumors, five had radiographic tumor reduction, including one patient with a confirmed PR. Shares of Blueprint (NASDAQ:BPMC) closed Tuesday at $30.34, down $5.16, or 14.5 percent.
Cara Therapeutics Inc., of Stamford, Conn., said it completed patient enrollment for the multidose phase of its adaptive phase II/III trial of kappa opioid receptor-targeting I.V. CR845 in dialysis patients suffering from moderate to severe uremic pruritus. Data from the eight-week part A of the study, expected in the first quarter of 2017, will determine the optimal dosing for planned registration trials.
Cellular Biomedicine Group Inc., of Shanghai, said it was cleared to start patient enrollment in China for its CARD-1 phase I study testing its C-CAR011 construct of CD19 chimeric antigen receptor T-cell therapy in diffuse large B-cell lymphoma (DLBCL). The dose-escalation trial will use the traditional 3x3 design to evaluate the safety, efficacy and persistence of C-CAR011 in refractory DLBCL patients. Final data from the study are expected in the second half of 2017.
Celsion Corp., of Lawrenceville, N.J., presented results from an independent retrospective analysis conducted by the NIH on the intent-to-treat population of the company’s HEAT study, a 701-patient study of heat-activated liposomal encapsulated doxorubicin product Thermodox in combination with radiofrequency ablation (RFA) in hepatocellular carcinoma, at the Scientific Assembly and Annual Meeting of the Radiological Society of North America in Chicago. The analysis, which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome, concluded that increased burn time per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with RFA plus Thermodox, compared to patients treated with RFA alone. More specifically, the analysis showed that a one unit increase in RFA duration per tumor volume improved OS by 20 percent in patients treated with optimized RFA plus Thermodox vs. RFA alone. Celsion is advancing Thermodox in the ongoing phase III OPTIMA study.
Corbus Pharmaceuticals Holdings Inc., of Norwood, Mass., said it is launching a one-year, open-label extension study of the ongoing phase II study of Resunab (JBT-101) for the treatment of skin-predominant dermatomyositis, following submission and review by the FDA. The goal of the extension is to provide all enrolled subjects with the option of receiving JBT-101 for one year after they complete the four-month, double-blind, placebo-controlled portion of the study and to collect long-term safety and efficacy data. The safety and efficacy endpoints used in the double-blinded, placebo-controlled portion of the study will be assessed throughout the one-year extension study. JBT-101 is a synthetic oral endocannabinoid-mimetic drug that preferentially binds to the CB2 receptor expressed on activated immune cells and fibroblasts.
Cytori Therapeutics Inc., of San Diego, said data published in Current Research in Translational Medicine details two-year follow-up of patients treated with a single administration of ECCS-50 in the SCLERADEC-I pilot trial of Cytori Cell Therapy in patients with hand dysfunction associated with scleroderma. Data showed key clinical benefits reported at the six-month time point of the trial were sustained at two years (follow-up range of 22-30 months). The primary endpoint, Cochin Hand Function Score, improved 62.5 percent over baseline (18.6±13.8 at two years vs. 48.5±10.8; p<0.0001). Key secondary endpoints also improved from baseline. Specifically, pain was reduced from 59.4±17.2 at baseline to 29.5±25.2 at two years (p=0.02); scleroderma-associated disability was reduced by 51.1 percent (0.7±0.5 vs. 1.4±0.3; p=0.0051); and Raynaud’s Condition Score improved by 88.3 percent (0.8±0.9 vs. 7.2±0.9; p<0.0001).
Eiger Biopharmaceuticals Inc., of Palo Alto, Calif., said it filed an IND for exendin 9-39, in development for subcutaneous administration to treat post-bariatric hypoglycemia (PBH). Eiger gained rights to the drug from Stanford University, which had previously tested intravenously administered exendin 9-39 in PBH and a subcutaneous injection study involving single ascending doses of exendin 9-39. Eiger currently is sponsoring a multiple ascending-dose study. Exendin 9-39 is a 31-amino acid peptide that selectively targets and blocks GLP-1 receptors.
Kempharm Inc., of Coralville, Iowa, said its IND was accepted by the FDA, with trials set to start next year testing KP201/IR, a single-entity benzhydrocodone HCl immediate-release abuse-deterrent prodrug for the treatment of acute pain.
Momenta Pharmaceuticals Inc., of Cambridge, Mass., said the confirmatory phase III study of M923, a biosimilar Humira (adalimumab, Abbvie Inc.) candidate developed in collaboration with Baxalta, now part of Dublin-based Shire plc, in patients with moderate to severe chronic plaque psoriasis, met its primary endpoint. The proportion of subjects in the study who achieved the primary endpoint, at least 75 percent reduction in the Psoriasis Area and Severity Index (PASI-75) following 16 weeks of treatment, was equivalent between M923 and Humira. The estimated difference in responders was well within the pre-specified confidence interval, confirming equivalence. Equivalence was also achieved in all secondary efficacy endpoints, including the achievement of PASI-50, PASI-90, proportion achieving clear or near-clear skin, and change from baseline in absolute PASI score. Adverse events were comparable in terms of type, frequency and severity, and were consistent with the published safety data for Humira.
Novan Inc., of Morrisville, N.C., reported top-line results from its phase II trial of SB206 for the treatment of genital warts caused by human papillomavirus, or HPV. The highest dose tested, SB206 12 percent, demonstrated a statistically significant improvement (p<0.05) in the incidence of complete clearance of all baseline warts compared to vehicle treatment after 12 weeks in both the intent-to-treat (ITT) and per-protocol analyses. In the ITT analysis, 33 percent of patients achieved complete clearance of all warts by week 12 when treated with SB206 12 percent once daily, compared to 4 percent for patients in the vehicle once-daily group (p=0.0099). In the per-protocol analysis containing patients who completed a full 12 weeks of dosing, 42 percent of patients achieved complete clearance of all warts when treated with SB206 12 percent once daily, compared to 7 percent in the vehicle group (p=0.0200). The once-daily treatment arms were generally well-tolerated, including the 12 percent once-daily dose. Novan plans to discuss the development program with the FDA in the first half of next year and could initiate pivotal trials in the second half of 2017.
Novo Nordisk A/S, of Bagsvaerd, Denmark, reported results from the DEVOTE long-term, randomized, double-blind, event-driven trial conducted to confirm the cardiovascular safety of Tresiba (insulin degludec) compared to insulin glargine U100 when added to standard of care. In the trial, more than 7,500 people with type 2 diabetes at high risk of major adverse cardiovascular events were treated for a period of about two years. The trial achieved its primary endpoint by demonstrating noninferiority of major adverse cardiovascular events (MACE) with Tresiba compared to insulin glargine U100, confirming the results of the interim analysis submitted to the FDA in 2015 and serving as the basis for approval of Tresiba and Ryzodeg 70/30.
Nymox Pharmaceutical Corp., of Hasbrouck Heights, N.J., said phase III results confirmed that patients who received fexapotide as their initial treatment for benign prostatic hyperplasia (BPH) had superior efficacy results as early as 10 days compared to control patients who received placebo or who had prior history of other BPH medical treatments. The new results, based on an analysis of the company’s NX02-107, NX02-0018, NX02-0020 and NX02-0022 trials, indicate that fexapotide was highly efficacious for first-line treatment of BPH. In total, 390 treatment-naive patients had improvements greater than previously treated BPH patients as early as 10 days post-treatment (p<0.02) and at one month (p<0.04), three months (p<0.001), six months (p<0.001), one year (p<0.01) and at long-term (3.5 years) follow-up (p<0.003). The levels of mean change from baseline pre-treatment ranged from 6.49 to 8.88 points improvement in the AUA BPH Symptom Score. Those previously untreated patients who received a single injection of fexapotide 2.5 mg also had statistically significant superior improvements compared to patients who received placebo treatments, as early as 10 days post-treatment (p<0.001) and at several time points also including the long-term (3.5 years) follow-up extension (p<0.001).
Oncomed Pharmaceuticals Inc., of Redwood City, Calif., presented phase I data at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, showing that its anti-DLL4/VEGF bispecific and anti-RSPO3 antibodies hit the safety goals, with single-agent doses for both agents identified. As of the data cut-off of Oct. 17, a total of 51 patients with advanced solid tumors had received single-agent doses ranging from 0.5 to 12.5 mg/kg every three weeks in the phase Ia trial of the anti-DLL4/VEGF bispecific antibody, with two of the 46 evaluable patients (4 percent) showing unconfirmed partial responses, while another 16 patients (35 percent) achieved stable disease. The partial responses occurred in patients with ovarian cancer and uterine carcinosarcoma. As of data cutoff of Oct. 11, 23 patients in the anti-RSPO3 phase Ia/Ib trial were evaluable for safety and 15 patients were evaluable for antitumor activity. In the single-agent phase Ia portion of the trial, five of 11 patients achieved stable disease and three of those five patients were RSPO3 high, with RSPO3 levels in a fourth patient slightly below the current cut point of Oncomed’s CLIA-validated biomarker assay. In the phase Ib portion, three of four evaluable colorectal cancer patients who received the combination of anti-RSPO3 and FOLFIRI achieved stable disease.
Oramed Pharmaceuticals Inc., of Jerusalem, said it concluded a phase Ib study of ORMD-0901, its oral GLP-1 analogue in type 2 diabetes, showing the drug to be safe and well-tolerated. In addition, the active oral GLP-1 arms of the study showed encouraging trending efficacy, the company said, and a phase IIb study is expected to start in 2017.
VBL Therapeutics Ltd., of Tel Aviv, Israel, reported top-line results from its exploratory phase II study of gene therapy candidate VB-111 (ofranergene obadenovec) in patients with advanced, differentiated thyroid cancer. As previously announced, the trial met its primary endpoint, which was defined as 25 percent progression-free survival at six months (PFS-6), in heavily pretreated patients with late-stage disease. A dose-dependent response was seen, with 35 percent of patients reaching PFS-6 in the therapeutic dose cohort vs. 25 percent in a low-dose cohort. Although the trial included a small number of patients and was not powered to show overall survival (OS) differences, the new data show a dose-response and evidence of an OS benefit in the cohort of patients treated with multiple therapeutic doses of VB-111, compared to patients who received a single low dose of VB-111 (mOS 761 days vs. 469 days; p=0.096). Only one patient remained alive in the low-dose cohort, compared to a tail of about 50 percent in the high-dose group.