Achieve Life Sciences Inc., of Bothell, Wash., reported results from a bioavailability study of the 3-mg dose of cytisine, which is being developed for smoking cessation. In 24 healthy volunteers, cytisine had bioequivalence when administered with or without food. Achieve recently started a multidose, pharmacokinetic and pharmacodynamics study of the 1.5-mg and 3-mg doses of cytisine for 25 days, the results of which are expected in the first quarter of 2018. Achieve plans to start a phase III program for the drug in mid-2018.
Akcea Therapeutics Inc., of Cambridge, Mass., an affiliate of Ionis Pharmaceuticals Inc., of Carlsbad, Calif., started a phase II trial for AKCEA-ANGPTL3-LRx, an antisense drug designed to reduce angiopoietin-like 3, in patients with familial chylomicronemia syndrome. Top-line results from the 13-week study are expected in 2018. Akcea plans to start additional phase II trials testing the drug in patients with familial partial lipodystrophy and homozygous familial hypercholesterolemia shortly.
Amgen Inc., of Thousand Oaks, Calif., reported subgroup analyses at the American Heart Association Scientific Sessions in Anaheim, Calif., from the Repatha (evolocumab) cardiovascular outcomes study (FOURIER) that showed the addition of Repatha to statin therapy improved clinical outcomes with significant reduction of cardiovascular (CV) events, such as heart attack and stroke, in high-risk patients with peripheral artery disease (PAD), and in patients with a history of heart attack. One analysis showed the addition of Repatha to statin therapy improved clinical outcomes with significant reduction of CV events in patients with a history of PAD. Because of their greater baseline risk of CV events, there was a numerically greater absolute risk reduction at 2.5 years in patients with PAD (ARR 4.1 percent, 95 percent CI 2.5-6.7) relative to those without PAD (ARR 1.5 percent, 95 percent CI 0.7-2.2). A separate analysis investigated the efficacy of Repatha in high-risk patients who have experienced a prior heart attack. In that analysis, the ARR was greater (~3 percent ARR over three years) in patients with a history of heart attack within two years compared to those whose heart attack was more than two years past (ARR 1 percent). No new safety concerns were identified in those analyses. (See BioWorld Today, March 20, 2017.)
Beigene Ltd., of Beijing, China, started a phase III trial testing BGB-3111, a Bruton's tyrosine kinase inhibitor, in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. One cohort will enroll 420 patients without a 17p deletion, comparing BGB-3111 to bendamustine and Rituxan (rituximab, Roche Holding AG/Biogen Inc.), using progression-free survival (PFS) as the primary endpoint and overall response rate (ORR), duration of response (DOR), overall survival (OS) and patient-reported outcomes as secondary endpoints. A second cohort will enroll patients with 17p deletion. Beigene also started a pivotal phase II trial of BGB-3111 in combination with Gazyva (obinutuzumab, Roche Holding AG) in approximately 210 patients with relapsed or refractory follicular lymphoma. The trial will compare the combination to Gazyva alone, measuring ORR as the primary endpoint and DOR, PFS, OS and time to response as secondary endpoints.
Boehringer Ingelheim GmbH, of Ingelheim, Germany, and Eli Lilly and Co., of Indianapolis, reported results from a post-hoc analysis of the EMPA-REG OUTCOME trial testing Jardiance in more than 7,000 patients with type 2 diabetes and peripheral artery disease at the American Heart Association (AHA) Scientific Sessions 2017 in Anaheim, Calif., which was simultaneously published online in the AHA's journal, Circulation. Jardiance reduced the risk of cardiovascular death by 43 percent and the risk of death from any cause by 38 percent. The drug also reduced the risk of hospitalization for heart failure by 44 percent. The risk of the composite endpoint of cardiovascular death, nonfatal heart attack or nonfatal stroke was reduced by 16 percent. New or worsening kidney disease was reduced by 46 percent. Also at the meeting, Boehringer Ingelheim reported two new analyses of the phase III RE-VERSE AD trial testing Praxbind (idarucizumab) in reversing the anticoagulant effect of Pradaxa (dabigatran etexilate mesylate) in patients in diverse emergency situations. Of the 137 patients enrolled in the trial with a gastrointestinal (GI) bleed, Praxbind produced a complete reversal of the anticoagulant effect of Pradaxa in more than 95 percent of patients with a median time to stop bleeding of less than three hours when the location of the GI bleed was known and 6.4 hours when the location was unknown. In patients requiring an urgent procedure, Praxbind reversed the anticoagulant effect of Pradaxa in 98 percent of patients with none of the patients experiencing periprocedural bleeding that was severely abnormal.
Imcyse SA, of Liege, Belgium, said it started recruiting patients in its phase Ib trial in insulin-dependent (type 1) diabetes. Imcyse is testing its Imotopes, specific modified peptides designed to induce cytotoxic T cells. Enrollment is expected to conclude by the middle of 2018, with results expected at the end of 2018.
Janssen Research & Development LLC, a unit of New Brunswick, N.J.-based Johnson & Johnson, reported a new analysis of the CANVAS program testing Invokana (canagliflozin) in type 2 diabetics with and without a history of cardiovascular (CV) disease at the American Heart Association (AHA) Scientific Sessions 2017 in Anaheim, Calif., which was simultaneously published online in the AHA's journal, Circulation. Patients with a history of CV disease had a hazard ratio of 0.98 while those with only risk factors for CV disease had a hazard ratio 0.82 comparing Invokana to placebo for the combined risk of CV death, nonfatal myocardial infarction and nonfatal stroke, consistent with the previously reported hazard ratio of 0.82 for the total cohort. Invokana lowered the risk of hospitalization due to heart failure and reduced the risk of the composite renal endpoint compared to placebo in each of the two CV disease subgroups.
Medicenna Therapeutics Corp., of Toronto, reported combined data from phase I and phase II trials of MDNA-55 in 66 patients with recurrent glioblastoma (rGBM) at the Cancer Prevention and Research Institute of Texas' Fifth Innovations in Cancer Prevention and Research Conference in Austin, Texas. MDNA-55 produced a median survival of 210 days. Patients with a partial or complete response had a median survival of 12.5 months with overall survival at six and 12 months of 71 percent and 57 percent, respectively. Medicenna is currently enrolling patients in a phase IIb trial for rGBM.
Neurocrine Biosciences Inc., of San Diego, said the full manuscript of the long-term safety and efficacy data from the blinded KINECT 3 phase III extension study evaluating Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia (TD) were published in the Journal of Clinical Psychiatry. The once-daily 80-mg and 40-mg doses continued to maintain symptom improvement and were generally well-tolerated over long-term dosing in patients with TD, a condition characterized by uncontrollable, abnormal and repetitive movements of the trunk, extremities and/or face. Ingrezza, a VMAT2 inhibitor, gained FDA approval for TD in April. (See BioWorld Today, 13, 2017.)
Oramed Pharmaceuticals Inc., of Jerusalem, said Israel's Ministry of Health granted the firm approval to start an exploratory study of its oral insulin capsule, ORMD-801, in patients with nonalcoholic steatohepatitis (NASH). The proposed three-month study will assess the effectiveness of ORMD-0801 in reducing liver fat content, inflammation and fibrosis in patients with NASH. Oramed plans on initiating the study in the coming month.
Puma Biotechnology Inc., of Los Angeles, said previously presented results from the ExteNET phase III trial of neratinib in patients with early stage HER2-positive breast cancer were published in The Lancet Oncology. Results demonstrated that after a median follow-up of 5.2 years, treatment with neratinib resulted in a 27 percent reduction of risk of invasive disease recurrence or death vs, placebo (p = 0.008). The five-year invasive disease-free survival (iDFS) rate for the neratinib arm was 90.2 percent and the five-year iDFS rate for the placebo arm was 87.7 percent. Neratinib, branded Nerlynx, gained FDA approval as an extended adjuvant therapy in patients with early stage, HER2-positive breast cancer. (See BioWorld, July 19, 2017.)
Replimune Group Inc., of Woburn, Mass., said the first cohort of patients was dosed in a phase I/II trial of RP-1, a candidate generated from the firm's Immulytic platform, in patients with advanced solid tumors. The first part of the trial will assess the safety of RP-1 and determine the optimal dose for use in the second part of the study, which will further evaluate safety and also assess the preliminary efficacy of RP-1 administered in combination with anti-PD1 therapy in cohorts of patients with specific solid tumor types.
Seres Therapeutics Inc., the University of Texas MD Anderson Cancer Center, and the Parker Institute for Cancer Immunotherapy will work together to evaluate the potential of Seres' microbiome therapies to improve the outcomes of cancer patients treated with currently available immunotherapy. The collaborators plan to run a randomized, placebo-controlled clinical study at MD Anderson, sponsored by the Parker Institute, in patients with advanced metastatic melanoma. The trial will evaluate the impact of an anti-PD-1 checkpoint inhibitor with adjunctive microbiome therapy on patient outcomes. Seres is developing SER-401, a preclinical oral microbiome therapy, to improve the efficacy and safety of immunotherapy. Financial terms of the deal were not disclosed, but Seres said it received an exclusive option, with predefined financial terms, to license intellectual property rights from MD Anderson related to the use of bacteria in combination with checkpoint inhibitors.
Tapimmune Inc., of Jacksonville, Fla., said it enrolled the final patient in a randomized phase II study of T-cell vaccine candidate TPIV-200 in triple-negative breast cancer. The four-arm study is designed to help determine the optimal vaccine dose and regimen to maximize the immune response generated against the vaccine's molecular target, folate receptor-alpha, a cancer cell biomarker that is highly correlated with disease recurrence.
Tracon Pharmaceuticals Inc., of San Diego, said results from a phase I trial of TRC-102 (methoxyamine) and Fludara (fludarabine) in patients with advanced hematologic malignancies were published in Oncotarget. The study, which enrolled 20 patients – 17 had measurable disease – with chronic lymphocytic leukemia, follicular lymphoma, diffuse large B-cell lymphoma, plasma cell myeloma, mantle cell lymphoma or anaplastic large cell lymphoma, showed that the combination of TRC-102 and Fludara produced evidence of tumor DNA damage that appeared to correlate with antitumor activity. Four of the 17 patients (24 percent) experienced a partial response to treatment, and eight additional patients (47 percent) had stable disease.
Zealand Pharma A/S, of Copenhagen, Denmark, said all subjects have been enrolled and dosed in a pharmacokinetic trial with glepaglutide, its long-acting GLP-2 analogue, under an IND for the treatment of short bowel syndrome. Following positive results from a phase II trial in June indicating a longer than expected half-life for glepaglutide, Zealand initiated the ongoing trial to investigate the potential for less than once-daily dosing. A total of 75 subjects have been enrolled. Results are expected in the first quarter of next year.