Responsible personalised medicine: Exploring the ethical, legal, social, political and economic issues of manufacturing, distribution, access and reimbursement. A Report of the Responsible Personalised Medicine Project, UCL Future Targeted Manufacturing in Healthcare Hub

This report provides an overview of the ethical, legal, social, political and economic (ELSPE) issues underpinning the “manufacturing, business and regulatory challenges” that confront the development and delivery of affordable and accessible new targeted biological medicines. We specifically focus on the evolving definitions and its implication for the public understanding of personalised medicine (section 1), issues of manufacturing and distribution of Personalised Therapies (section 2) and institutional readiness (section 3) specifically focusing on emerging regulatory and reimbursement pathways (section 3.2) and how these are shaping or being shaped by ‘real world evidence’ (section 3.3). This is followed by our reflection on the implications of and for the entangled, complex and contingent interrelationships between personalised medicine, society and responsibility (section 4). Finally we conclude with discussion of the gaps and priorities for future ELSPE research on manufacturing of advanced biotherapeutics in terms of access, reimbursement, skills and infrastructure, regulation, responsible research and innovation (RRI) and the international political economy of emerging personalised medicine markets (section 5). This is a necessarily narrower review of the spectrum of ELSPE issues that attend personalised medicine activities and reflects this report’s aims to focus on those aspects of personalised medicine addressed by the UCL’s Future Targeted Manufacturing in Healthcare Hub

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

The Prevalence of Pulmonary and Upper Respiratory Tract Symptoms and Spirometric Test Findings Among Newspaper Pressroom Workers Exposed to Solvents

To investigate the relationship between exposure to organic solvents and the presence of pulmonary and upper respiratory tract mucous membrane symptoms, we conducted a cross-sectional study of 215 newspaper pressroom workers who were occupationally exposed to organic solvent and lubricant mixtures. Thirty-four compositors, who were not occupationally exposed to the solvents or lubricants, served as controls. Pressroom workers and compositors underwent spirometric testing and were also asked about the presence of cough, phlegm, hemoptysis, dyspnea, wheezing, chest tightness, nose or throat irritation, eye irritation, and sinus trouble. The spirometric results did not significantly differ between the two groups. However, the pressroom workers were significantly more likely to report pulmonary or upper respiratory tract mucous membrane symptoms than were compositors (P \u3c 0.005). An exposure-response relationship could be demonstrated when comparing the number of solvents exposed with the total number of symptoms (P \u3c 0.001). Similarly, an exposure-response relationship could be demonstrated when comparing the frequency of use of each of the seven solvents with the total number of symptoms (P \u3c 0.002). Each of these findings was supported in a multivariable linear regression model that adjusted for potential confounders such as age, smoking history, and number of years in the industry. A high prevalence of these symptoms was reported even though the degree of exposure to solvents and lubricants was within the current permissible exposure limits