Characterization of annual disease progression of multiple sclerosis patients: A population-based study.

Background: Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching the milestone.

Medicines Adaptive Pathways to Patients (MAPPs): A Story of International Collaboration Leading to Implementation.

After nearly a decade of discussion, analysis, and development, the Medicines Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance from regulators, industry, patients, and payers, with the first live pilot project initiated under the guidance of the European Medicines Agency in 2014. Although it is a significant achievement to see the first asset being placed into human trials under an adaptive pathway, there is much to be learned regarding the multinational and multi-stakeholder effort that has driven the growing acceptance of MAPPs as a methodology and concept, as well as the need for continued and increasing international collaboration to foster the wider adoption of MAPPs. Changes in available science and technology, as well as a number of challenges in the current system, outlined in this paper, are transforming approaches to medicines development and approval.

Comparison of Stakeholder Metrics for Traditional and Adaptive Development and Licensing Approaches to Drug Development.

This study evaluates whether an adaptive development and licensing approach to drug development, compared with approaches widely used today, might have tangible advantages across stakeholder groups, thereby facilitating the future adoption. Details involving actual and modeled clinical development and licensing programs for 3 case studies were used as inputs into a discounted cash flow spreadsheet model. Outputs included net present value and expected net present value, which are metrics considered as key incentives for pharmaceutical developers, and change in patient access over the product life and numbers of appropriately and inappropriately treated patients, which are metrics considered as key incentives for regulators, patients, and prescribers.

DX-88 and HAE: a developmental perspective.

An example of an approach to the developmental philosophy of novel recombinant products is explored by using the exemplar of Hereditary Angioedema (HAE). Plasma kallikrein is believed to be an important mediator of angioedema in patients with genetic deficiency of C1 esterase inhibitor (HAE patients). DX-88, a novel Kunitz domain produced by phage display (a powerful method of generating novel binders to potentially therapeutic targets), is a potent and selective inhibitor of plasma kallikrein which in early clinical studies demonstrates a useful efficacy/safety ratio in the treatment of acute attacks of HAE.