Alexion Pharmaceuticals Inc., of Cheshire, Conn., initiated separate multinational, placebo-controlled trials to evaluate the safety and efficacy of eculizumab (Soliris) in patients with relapsing neuromyelitis optica (NMO) and those with refractory generalized myasthenia gravis (MG). Both disorders are caused by uncontrolled complement activation. The primary endpoint of the NMO study is time to first relapse and relapse risk reduction. Secondary endpoints include safety, tolerability and additional efficacy measures. Eculizumab received orphan drug designation from the FDA and orphan medicinal product designation from the Committee for Orphan Medicinal Products of the EMA to treat NMO. The MG trial is assessing the efficacy of eculizumab compared to placebo on motor function, as measured by the improvement in MG-Activities of Daily Living score at 26 weeks. Secondary endpoints include safety, tolerability and additional efficacy measures.
Bayer HealthCare Pharmaceuticals Inc., of Whippany, N.J., and Onyx Pharmaceuticals Inc., of South San Francisco, an Amgen Inc. subsidiary, reported that results from the phase III DECISION trial were published online in The Lancet. The data demonstrated that Nexaxar (sorafenib) tablets significantly extended the time patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma that is refractory to radioactive iodine treatment lived without their disease worsening (progression-free survival; PFS). Based on those data, the drug was approved by the FDA in November 2013. Those patients previously had limited approved treatment options.
Celsion Corp., of Lawrenceville, N.J., said updated results from the post hoc analysis of 701 patients in the HEAT study and a review of the final study design of the phase III OPTIMA study, both exploring the company's heat-activated liposomal encapsulation of doxorubicin, known as Thermodox, in combination with radiofrequency ablation (RFA) to treat hepatocellular carcinoma (HCC) were presented at the European Conference on Interventional Oncology in Berlin. Data from the HEAT study suggested Thermodox may improve overall survival (OS), compared to RFA control, in patients whose lesions undergo RFA treatment for 45 minutes or longer. Patients with single HCC lesions (64.4 percent of the HEAT study population) from both size cohorts (3-5 cm and 5-7 cm), representing a subgroup of 285 patients, showed a 50 percent improvement in OS, with a hazard ratio of 0.666 (95 percent CI 0.434 - 1.022) and a "p" value of 0.06. Median OS for that subgroup was not reached. Celsion plans to conduct the OPTIMA study in up to 100 centers in 15 countries, with enrollment scheduled to begin midyear. In September, Celsion initially reported positive OS findings from a subgroup analysis of HEAT participants after the study missed its primary endpoint earlier in the year. (See BioWorld Today, Feb. 1, 2013, and Sept. 17, 2013.)
Cynapsus Therapeutics Inc., of Toronto, reported positive data from its recently completed CTH-104 healthy volunteer pilot study of a single 25-mg sublingual strip (APL-130277) dose of apomorphine. APL-130277 is an easy-to-administer, fast-acting reformulation of apomorphine, which is the only approved drug in the U.S., Europe, Japan and other countries for the acute rescue of "off" motor symptoms of Parkinson's disease. The study was a single-dose, single-arm, placebo-controlled, healthy volunteer pharmacokinetic study, which was designed to examine the pharmacokinetic profile of the 25-mg dose of APL-130277. In total, 13 subjects completed the study (11 active and two placebo).
Durata Therapeutics Inc., of Chicago, said it began enrollment of a phase IIIb trial to evaluate the efficacy and safety of its investigational product, Dalvance (dalbavancin) for injection, in a single 1,500-mg dose infused over 30 minutes in adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive bacteria. The study compares a single dose of Dalvance with the once-weekly dosage regimen of Dalvance in adult patients with ABSSSI known or suspected to be caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Approximately 410 adult patients will be randomized to receive either one 1,500 mg single dose of Dalvance on day one or two doses of Dalvance with 1,000 mg on day one followed by 500 mg on day eight. For presumed gram-negative pathogens, only intravenous (I.V.) aztreonam may be administered at randomization; for suspected anaerobic pathogens, oral or I.V. metronidazole may be used. The primary outcome measure will be the percentage of patients in each treatment group who demonstrate a clinical response at 48 hours to 72 hours after the initiation of therapy. The study was designed to meet the new standards required by regulatory authorities for antibiotic development in the U.S.
Merck KGaA, of Darmstadt, Germany, said data from the phase IIIb SPARK study showed it met its primary endpoint, with results from the first 26 weeks demonstrating that the addition of Kuvan (sapropterin dihydrochloride) to a phenylalanine-restricted diet in children younger than 4 who have phenylketonuria (PKU) and previously have been shown to be responsive to Kuvan significantly increased tolerance to phenylalanine compared with a phenylalanine-restricted diet alone. SPARK was conducted as a post-authorization measure and results will be submitted to the EMA. Merck gained European rights to the product from San Rafael, Calif.-based Biomarin Pharmaceutical Inc., which sells Kuvan in the U.S. for PKU, an autosomal recessive genetic disorder caused by a defect in the phenylalanine hydroxylase enzyme.
Oramed Pharmaceuticals Inc., of Jerusalem, reported detailed results from its phase IIa trial of OMRD-0801, an orally ingestible insulin capsule, in type 2 diabetes at the GTC Diabetes Summit in Cambridge, Mass. Results showed that the oral insulin appeared to be safe and well tolerated for the dosing regimen tested, with no hypoglycemic events occurring in any treatment group and no treatment-related adverse events observed. Although the study was not powered to show statistical significance, there were trends observed showing a pattern of well-defined and short-term increases in plasma insulin and decrease in blood glucose.
Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., said it completed enrollment in the chemotherapy-naïve cohort in its phase II trial of PSMA ADC. That cohort of 36 prostate cancer patients, all of whom progressed on hormonal therapies, was added to the phase II study following positive response to PSMA ADC in patients in the chemotherapy-experienced setting. The drug comprises a fully human monoclonal antibody selectively targeting prostate-specific membrane antigen linked to a chemotherapeutic drug using technology licensed from Bothell, Wash.-based Seattle Genetics Inc.
Vernalis plc, of Winnersh, U.K., reported the results from a phase Ib/II proof-of-concept study of V81444, an A2A antagonist which has potential applications for the treatment of Parkinson's disease, attention deficit hyperactivity disorder (ADHD) and other disorders of the central nervous system. The randomized, double-blind, placebo-controlled, two-period crossover study was designed to evaluate the safety, tolerability and pharmacokinetics of V81444 dosed twice daily for 14 days and was conducted in adult patients with a confirmed diagnosis of ADHD. The study enrolled 31 patients (safety population) and, in addition to evaluating safety, tolerability and pharmacokinetics, measured the efficacy of V81444 using the ADHD Rating Scale (primary measure), PERMP-P and Clinical Global Impression (CGI) assessments (secondary measures). The compound achieved a statistically significant improvement in the number of correct scores in PERMP-P measure (p = 0.019) compared to placebo. Although not statistically significant, V81444 also showed improvements in both the ADHD Rating Scale and CGI.