Actinogen Medical Ltd., of Sydney, reported data at the Alzheimer's Association International Conference in Toronto, showing its lead compound, Xanamem, an orally administered 11beta-HSD1 inhibitor, demonstrated in phase I that it significantly inhibited production of cortisol in healthy volunteers and successfully crossed the blood-brain barrier. A separate study, the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing, sponsored by the CSIRO and a number of Australian universities, showed a correlation between elevated cortisol in the blood of a healthy aged population and the subsequent development of Alzheimer's disease in those individuals.
Anavex Life Sciences Corp., of New York, reported efficacy data through 31 weeks from the ongoing ANAVEX 2-73 phase IIa study in mild to moderate Alzheimer's patients at the Alzheimer's Association International Conference in Toronto. Overall, results demonstrated what the firm said appears to be a converging and consistent response for all quantitative endpoints, including cognitive and functional measures: Mini Mental State Examination, Alzheimer's Disease Co-operative Study – Activities of Daily Living, Cogstate and electroencephalographic activity and event-related potentials. Anavex also noted HAM-D data showing beneficial effects of ANAVEX 2-73 on insomnia, agitation and anxiety at 31 weeks, which might suggest an additional role for the drug in the amelioration of behavioral and psychological symptoms of dementia.
Bavarian Nordic A/S, of Copenhagen, initiated a phase I trial of MVA-BN YF, a vaccine candidate designed to protect against yellow fever virus. The placebo-controlled, double-blind trial, sponsored by the National Institute of Allergy and Infectious Diseases, is evaluating whether the vaccine is safe and tolerable and induces a human immune response indicating a potential to prevent yellow fever virus infection. The study is expected to enroll 90 healthy volunteers between the ages of 18 and 45, who will be divided into six groups of 15 participants each. One group will receive the currently licensed yellow fever vaccine and the other five will receive MVA-BN YF, with or without ISA 720 adjuvant.
Boehringer Ingelheim Pharmaceuticals Inc., a unit of Boehringer Ingelheim GmbH, of Ingelheim, Germany, initiated the INMARK study to assess the effect of its oral kinase inhibitor, Ofev (nintedanib), on certain blood biomarkers that may identify greater scarring and loss of lung function in patients with idiopathic pulmonary fibrosis (IPF). INMARK will examine the effect of Ofev, approved by the FDA in 2014 to treat IPF, on the rate of change of biomarkers associated with extracellular matrix compared to placebo. Two-thirds of patients will be treated with placebo for the first 12 weeks of the trial and one-third will be treated with Ofev, dosed at 150 mg twice daily. Following the placebo-controlled period, all patients in the trial will continue on Ofev for 40 weeks. The study plans to enroll 350 patients across sites in Australia, Asia, Europe and North America.
Flugen Inc., of Madison, Wis., initiated the first phase I trial of its H3N2 Redeeflu universal influenza vaccine. The randomized, blinded, dose-ranging study is expected to enroll 96 healthy adults 18 to 49 years of age. In addition to the primary goal of evaluating the vaccine's safety, the study will assess antibody and T-cell responses induced by the vaccine. (See BioWorld Today, Aug. 26, 2015.)
Gamida Cell Ltd., of Jerusalem, said the first patient with sickle cell disease (SCD) was transplanted in a phase I/II study of Cordin, its ex vivo expanded cell graft to treat patients with chronic non-malignant diseases. In a previous phase I/II study in SCD, the expanded graft was transplanted along with a non-manipulated umbilical cord blood unit in a double graft configuration. The new phase I/II study updates the protocol from the previous study, transplanting Cordin as a standalone graft that is expanded from one full umbilical cord blood unit and enriched with stem cells, using the company's technology.
Karyopharm Therapeutics Inc., of Newton, Mass., said data from its phase Ib trial evaluating lead candidate, selinexor (KPT-330), in patients with advanced refractory bone or soft tissue sarcoma were published online in the Journal of Clinical Oncology. The paper reported findings from a 54-patient study that evaluated the pharmacokinetics, pharmacodynamics, safety and efficacy of selinexor and determined the recommended phase II dose. The data, presented at the American Society for Clinical Oncology 2015 annual meeting, showed that, of 52 evaluable patients, 30 (58 percent) showed a best response of stable disease (SD), with 17 (33 percent) experiencing durable SD (≥4 months). Single-agent oral selinexor was determined to be safe and well tolerated at 60 mg twice per week on an intermittent (three weeks on, one week off) dosing schedule. Karyopharm also said that selinexor received orphan drug designation from the FDA to treat soft tissue sarcoma.
Neurovance Inc., of Cambridge, Mass., said its phase IIb trial of centanafadine SR (CTN), a non-stimulant to treat adults with attention deficit hyperactivity disorder (ADHD), met both the primary and secondary safety and efficacy endpoints. Patients who received CTN dosed at 400 mg showed a -15.1 point change from baseline in the primary endpoint vs. a -8.1 point change observed with placebo, resulting in a statistically significant difference of -7.0 (p<0.001) and an effect size of 0.6, which was within the range of pivotal trials of approved stimulants – the drugs most frequently prescribed in the U.S. to treat ADHD. The three-week, placebo-controlled, crossover trial in 85 adult ADHD patients, conducted at four U.S. sites, also showed the 400 mg dose was generally well tolerated. Rates of insomnia and loss of appetite were lower than typically seen with stimulants.
Pluristem Therapeutics Inc., of Haifa, Israel, said it plans to conduct a phase III trial assessing the effect of its PLX-PAD cells on recovery following surgery for femoral neck fracture, the most common form of hip fracture. Pluristem plans to meet with the FDA this year to discuss the phase III protocol, which the company previously submitted to the EMA following consultation with the adaptive pathways project group. (See BioWorld Today, Aug. 13, 2015.)
Psivida Corp., of Watertown, Mass., said the first phase III trial of Medidur to treat posterior uveitis continued to meet its primary endpoint, prevention of disease recurrence, with high statistical significance through 12 months of follow-up (p < 0.00000001, intent to treat analysis). Through 12 months, posterior uveitis recurred in 26.4 percent of eyes treated with a Medidur injection compared to 85.7 percent of eyes that received a sham injection. Medidur was generally well tolerated through the last follow-up visit. The average increase in intraocular pressure (IOP) at 12 months was 0.6 mmHg higher in Medidur-treated eyes than control eyes (1.3 mmHg vs. 0.7 mmHg, respectively), but Psivida said the incremental risk of elevated IOP for Medidur-treated eyes compared to control eyes was lower than during the first six months for certain groups, including those with more than 21 mmHg (8.3 percent vs. 10.9 percent) and those with more than 25 mmHg (5.1 percent vs. 11.3 percent). Elevated IOP was generally well treated with eye drops, and the percentage of eyes requiring incisional surgery to reduce IOP was essentially the same in Medidur-treated and control eyes through last follow-up (4.6 percent vs. 4.8 percent). (See BioWorld Today, Dec. 23, 2015.)
Recro Pharma Inc., of Malvern, Pa., said its phase III trial evaluating intravenous (I.V.) meloxicam (N1539) to treat acute postoperative pain following bunionectomy surgery achieved the primary endpoint, with a statistically significant difference in Summed Pain Intensity Difference (SPID) over the first 48 hours (SPID48) compared to placebo. The study also achieved 15 of 19 secondary endpoints, including statistically significant differences in SPID6 (p=0.0153), SPID12 (p=0.0053), SPID24 (p=0.0084), SPID24-28 (p=0.0050), time to first use of rescue medication (p=0.0076) and other rescue use and pain relief metrics during the first 48 hours, compared to placebo. The parameters of "time to perceptible pain relief," "time to meaningful pain relief," "proportion of patients with >50 percent improvement at 6 hours" and "patient's global assessment of pain control at 24 hours" were not significantly different between treatment groups. The multicenter, double-blind, placebo-controlled trial enrolled 201 patients, who were randomly assigned to a postoperative regimen of I.V. meloxicam (30 mg bolus injection over 15-30 seconds) or placebo in a 1:1 ratio, once every 24 hours for up to three doses following bunionectomy surgery. No serious adverse events (AEs) or bleeding events occurred in patients treated with I.V. meloxicam. The most common AEs were nausea, headache, pruritus, constipation vomiting, dizziness, flushing and somnolence, and these were comparable to the placebo group, according to the company. Recro said it will submit additional data from the trial for presentation at a scientific conference or publication in a journal. A second phase III evaluating I.V. meloxicam following mini abdominoplasty surgery is ongoing, with top-line results expected by year-end.
Stemedica Cell Technologies Inc., of San Diego, said it opened enrollment in a phase Ila study testing a single, intravenous dose of allogeneic human mesenchymal stem cells in subjects with mild to moderate dementia due to Alzheimer's disease. The randomized, single-blind, placebo-controlled, crossover study will enroll about 40 patients diagnosed at least three months prior to enrollment, based on National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association Alzheimer's criteria.
Uniqure NV, of Lexington, Mass., presented updated data at the World Federation of Hemophilia meeting in Orlando, Fla., from a phase I/II trial showing that all patients in the low-dose cohort of AMT-060, its gene therapy for severe hemophilia B, had sustained improvements in their disease phenotype and continue to maintain durable levels of factor IX gene activity for up to 39 weeks post treatment. The study includes 10 patients, each receiving a one-time, 30-minute, intravenous infusion of AMT-060, without the use of corticosteroids.
Ultragenyx Pharmaceutical Inc., of Novato, Calif., said it completed patient enrollment in the phase III study of aceneuramic acid extended release (Ace-ER) to treat GNE myopathy and expects to report data from the study next year. The global, randomized, double-blind, placebo-controlled phase III is assessing the efficacy and safety of six grams per day of Ace-ER over 48 weeks in 89 patients. The primary endpoint is a comparison of active and placebo-treated patients from baseline to 48 weeks in the composite of upper extremity muscle strength as measured by hand-held dynamometry. Key secondary endpoints include the GNE myopathy-functional activity scale, or GNEM-FAS; a disease-specific patient-reported outcome that includes measures of mobility and upper-extremity function; a composite of lower extremity muscle strength; and other measures of lower-extremity muscle strength and function.