Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19.

Background: Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19.

Methods: Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC.

Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports.

Objective: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab.

Methods: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively.

Belimumab use during pregnancy: Interim results of the belimumab pregnancy registry.

Background: Belimumab is approved for active, autoantibody-positive systemic lupus erythematosus (SLE) and lupus nephritis, but limited data exist regarding its use in pregnancy. The Belimumab Pregnancy Registry (BPR, GSK Study BEL114256; NCT01532310) was created to evaluate pregnancy and infant outcomes following belimumab exposure.

Methods: Individuals with SLE exposed to belimumab from 4 months before and/or during pregnancy can enroll into the BPR.

Global Landscape of Benefit-Risk Considerations for Medicinal Products: Current State and Future Directions.

In the last decade there has been a significant increase in the literature discussing the use of benefit-risk methods in medical product (including devices) development. Government agencies, medical product industry groups, academia, and collaborative consortia have extensively discussed the advantages of structured benefit-risk assessments. However, the abundance of information has not resulted in a consistent way to utilize these findings in medical product development.

Mortality after admission with pneumonia is higher than after admission with an exacerbation of COPD.

https://bit.ly/3LyhnnC

A Framework for Safety Evaluation Throughout the Product Development Life-Cycle.

Evaluation of the safety profile of medicines is moving from a more reactive approach, where safety experts and statisticians have been primarily focusing on the review of clinical trial data and spontaneous reports, to a more proactive endeavor with cross-functional teams strategically evolving their understanding of the safety profile. They do this by anticipating the ultimate benefit-risk profile and its related risk management implications from the start of development. The proposed approach is based on assessments of integrated program-level safety data.

Treatment Patterns of New Users of Fluticasone Furoate/Vilanterol in Asthma and COPD in UK Primary Care: Retrospective Cohort Study.

Introduction: This retrospective database study explored treatment patterns and potential off-label prescribing among patients newly prescribed fluticasone furoate/vilanterol (FF/VI) in a UK primary care setting.

Methods: In Europe, FF/VI is approved in two strengths: 100/25 µg for adults with chronic obstructive pulmonary disease (COPD) and 100/25 µg or 200/25 µg for treatment of asthma in patients aged 12 or older. Using electronic health records from the Clinical Practice Research Datalink, new users of FF/VI or other inhaled corticosteroid/long-acting beta-agonist fixed-dose combination products were identified and classified into one of three groups: COPD diagnosis, asthma diagnosis, and other diagnosis (not COPD or asthma).

Recommendations for the Use of Social Media in Pharmacovigilance: Lessons from IMI WEB-RADR.

Over a period of 3 years, the European Union's Innovative Medicines Initiative WEB-RADR project has explored the value of social media (i.e., information exchanged through the internet, typically via online social networks) for identifying adverse events as well as for safety signal detection.

Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.

Introduction: Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria.

Objective: This study assessed the pharmacodynamic effects of 300-mg single-dose tafenoquine on the retina.

Methods: This phase I, prospective, multicenter, randomized, single-masked, placebo-controlled, parallel-group study was conducted between 2 February 2016 and 14 September 2017 at three US study centers.

Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA-B*5701 Screening as a Risk-Mitigation Measure.

Introduction: Human leukocyte antigen (HLA)-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4-8%.

Safety of biweekly α-antitrypsin treatment in the RAPID programme.

http://ow.ly/CVbz30lUBum

A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma.

Phosphoinositide 3-kinase (PI3K) is a lipid kinase involved in leukocyte recruitment and activation. Activation of PI3K has been linked to airway inflammation and asthma pathogenesis. This randomized, double-blind, placebo-controlled, crossover study investigated the efficacy, safety, tolerability, and pharmacokinetics of a PI3K inhibitor, nemiralisib (GSK2269557), in patients with persistent, uncontrolled asthma.

Patient Understanding of the Neuropsychiatric Risks Associated with Branded Bupropion Hydrochloride Products Used for Smoking Cessation.

Background: Bupropion hydrochloride (Zyban) is an effective aid to smoking cessation; however, its use has previously been associated with neuropsychiatric adverse events. Here we report results of the patient Knowledge, Attitudes, and Behavior survey that forms part of the Year 7 Risk Evaluation and Mitigation Strategy (REMS) assessment for Zyban.

Objective: Assess participants' understanding of the neuropsychiatric risks associated with branded bupropion hydrochloride products that are used for smoking cessation, as described in the Medication Guides.

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study.

Objective: To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS).

Methods: Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured.

Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics.

Key Points: Ion current kinetics are commonly represented by current-voltage relationships, time constant-voltage relationships and subsequently mathematical models fitted to these. These experiments take substantial time, which means they are rarely performed in the same cell. Rather than traditional square-wave voltage clamps, we fitted a model to the current evoked by a novel sum-of-sinusoids voltage clamp that was only 8 s long.

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants.

Purpose: Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants.

Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet.

Collaboration in pharmacovigilance: lamotrigine and fatal severe cutaneous adverse reactions - a review of spontaneous reports.

Pharmacovigilance presents many challenges, particularly when managing unpredictable, rare conditions, eg, severe cutaneous adverse reactions (SCARs). Such rare events are often only detected from spontaneous reports, which present their own limitations, particularly during a prolonged global launch schedule. GlaxoSmithKline's routine pharmacovigilance includes regular reviews of global adverse event (AE) reports and aggregate data from a central safety database.

Adjunctive use of anticoagulants at the time of percutaneous coronary intervention in patients with an acute coronary syndrome treated with fondaparinux: a multinational retrospective review.

Aim: This retrospective chart review was designed to evaluate physician adherence to the prescribing information for fondaparinux regarding adjunctive anticoagulant use during percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome (ACS).

Methods And Results: Medical record abstractors at each site obtained information regarding the use of fondaparinux and adjunctive anticoagulants during PCI. Physician adherence to fondaparinux prescribing information regarding the administration of an adjunctive anticoagulant during PCI was estimated using generalized estimating equations.

Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Neurite outgrowth inhibitor A (Nogo-A) is thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). A monoclonal antibody against Nogo-A showed a positive effect in the SOD1 mouse model of ALS, and a humanised form of this antibody (ozanezumab) was well tolerated in a first-in-human trial. Therefore, we aimed to assess the safety and efficacy of ozanezumab in patients with ALS.

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma.

Background: Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients.

Methods: Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma.

Effectiveness of Fluticasone Furoate-Vilanterol for COPD in Clinical Practice.

Background: Evidence for the management of chronic obstructive pulmonary disease (COPD) comes from closely monitored efficacy trials involving groups of patients who were selected on the basis of restricted entry criteria. There is a need for randomized trials to be conducted in conditions that are closer to usual clinical practice.

Methods: In a controlled effectiveness trial conducted in 75 general practices, we randomly assigned 2799 patients with COPD to a once-daily inhaled combination of fluticasone furoate at a dose of 100 μg and vilanterol at a dose of 25 μg (the fluticasone furoate-vilanterol group) or to usual care (the usual-care group).

Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network.

Purpose: To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients.

Methods: A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, Department of Veterans Affairs (VA) and an oncology practice network (Altos), and the PHARMO Database Network in The Netherlands. A common protocol was used to collect liver chemistry (LC) data from anti-VEGF initiation through 4 years of follow-up.

Progressive multifocal leukoencephalopathy in patients with systemic lupus erythematosus: a systematic literature review.

Objective: To determine risk factors for progressive multifocal leukoencephalopathy (PML) in systemic lupus erythematosus (SLE) patients, and understand how underlying disease or treatment for SLE may be associated with PML in this population.

Methods: Studies published in English between January 1, 1984 and October 31, 2014 that reported PML in adult SLE patients were included. Immunosuppression was defined as exposure to ≥1 immunosuppressant drug of interest at PML diagnosis: belimumab, rituximab, mycophenolate mofetil, azathioprine, cyclophosphamide, methotrexate and high-dose corticosteroids (>15 mg/day).