Drug repurposing for regenerative medicine and cosmetics: Scientific, technological and economic issues.

Regenerative medicine and cosmetics are currently two outstanding fields for drug discovery. Although many pharmaceutical products for regenerative medicine and cosmetics have received approval by official agencies, several challenges are still needed to overcome, especially financial and time issues. As a result, drug repositioning, which is the usage of previously approved drugs for new treatment, stands out as a promising approach to tackle these problems. Recently, increasing scientific evidence is collected to demonstrate the applicability of this novel method in the field of regenerative medicine and cosmetics. Experts in drug development have also taken advantage of novel technologies to discover new candidates for repositioning purposes following computational approach, one of two main approaches of drug repositioning. Therefore, numerous repurposed candidates have obtained approval to enter the market and have witnessed financial success such as minoxidil and fingolimod. The benefits of drug repositioning are undeniable for regenerative medicine and cosmetics. However, some aspects still need to be carefully considered regarding this method including actual effectiveness during clinical trials, patent regulations, data integration and analysis, publicly unavailable databases as well as environmental concerns and more effort are required to overcome these obstacles.

Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies.

The development of reprogramming technology to generate human induced pluripotent stem cells (iPSCs) has tremendously influenced the field of regenerative medicine and clinical therapeutics where curative cell replacement therapies can be used in the treatment of devastating diseases such as Parkinson's disease (PD) and diabetes. In order to commercialize these therapies to treat a large number of individuals, it is important to demonstrate the safety and efficacy of these therapies and ensure that the manufacturing process for iPSC-derived functional cells can be industrialized at an affordable cost. However, there are a number of manufacturing obstacles that need to be addressed in order to meet this vision. It is important to note that the manufacturing process for generation of iPSC-derived specialized cells is relatively long and fairly complex and requires differentiation of high-quality iPSCs into specialized cells in a controlled manner. In this chapter, we have summarized our efforts to address the main challenges present in the industrialization of iPSC-derived cell therapy products with focus on the development of a current Good Manufacturing Practice (cGMP)-compliant iPSC manufacturing process, a comprehensive iPSC characterization platform, long-term stability of cGMP compliant iPSCs, and innovative technologies to address some of the scale-up challenges in establishment of iPSC processing in 3D computer-controlled bioreactors.

Reimbursement and pricing of regenerative medicine in South Korea: key factors for achieving reimbursement.

In the South Korean health technology assessment system, prices of alternative medicines, incremental cost-effectiveness ratios in pharmaco-economic evaluations and patient access improvement systems such as risk-sharing agreements are the most important factors concerning the reimbursement of regenerative medicine (RM). Research and development companies in RM should review the key features of these medicines throughout the product development cycle to increase the probability of successful reimbursement. In addition, the South Korean government should take steps to improve the system to reflect the unique characteristics and value of RM in the reimbursement and pricing policy, to revitalize research and development, and increase patient access.

An Overview of the Tissue Engineering Market in the United States from 2011 to 2018.

IMPACT STATEMENT: This report seeks to provide an update of the current landscape of the tissue engineering market in the United States from an unbiased point of view by analyzing the financial reports provided by tissue engineering companies, as well as data from publicly available clinical trials with relevant tissue engineering applications.

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. OBJECTIVES: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology-specifically economic evaluation methods-in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. METHODS: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. RESULTS: Three key topics were identified and prioritised for discussion-uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. CLASSIFICATION CODE: I.

The Effect of a Pediatric Rare Disease on Subscriber Retention Rates for Commercial Health Insurers in the United States.

BACKGROUND: The advent of personalized medicine creates opportunities for regenerative therapies to deliver extended clinical benefit from a single administration. Policymakers and health insurers in the United States are evaluating coverage and payment arrangements for these therapies. One challenge involved in these evaluations is the perception that subscribers change insurers relatively often. However, the effect of pediatric rare diseases on retention rates for commercial health insurers has not been well studied. OBJECTIVE: To develop estimates for subscriber retention by a commercial insurer for up to 10 years. METHODS: Three population cohorts were examined: (1) all subscribers, (2) subscribers with any dependent aged 16 years or younger, and (3) subscribers with any dependent aged 16 years or younger diagnosed with a chronic rare disease that typically results in a debilitating state or high mortality, usually associated with high health care costs regardless of whether a treatment is available. The analysis was conducted for a sample of fully insured and self-insured group business within the commercial health insurance market for these study cohorts. The MarketScan Commercial Claims and Encounters research database covering the time period from January 1, 2007, through December 31, 2016, was used as the basis for the analysis. Subscribers were included in the family-based cohorts beginning with the first observed month with a dependent aged 16 years or younger and were retained in the analysis until the subscriber or insurer withdrew from the dataset (whichever came first). Subscribers were included in the family-based rare disease cohorts if their qualifying dependent was reported with at least 2 occurrences for any of the rare diseases studied. A Kaplan-Meier estimator was used to produce retention rates for all populations for up to 120 months. An adjustment for interval censoring was applied to the family-based cohorts. A log rank test with chi-square statistic was used to determine statistical significance. RESULTS: The analysis found that the subscriber retention rate within the self-insured groups was higher than within the fully insured groups (P < 0.0001). In addition, the probability of retaining subscribers with a dependent aged 16 years or younger compared with all subscribers was significantly greater (P < 0.0001). The analysis also found the probability of retaining subscribers with a qualifying dependent with a rare disease compared with subscribers with any dependent aged 16 years or younger was significantly greater (P < 0.0001). CONCLUSIONS: This study demonstrated that families with a child with a rare disease remained with their commercial health insurer longer than families who did not have a child with a rare disease. The analysis will be a useful resource when evaluating alternative payment arrangements and cost/benefit analyses of regenerative therapies that offer an extended duration of clinical benefit. DISCLOSURES: This study was sponsored by AveXis, which provided input into the study design, decided to submit the study results for publication, and performed an editorial review of the manuscript. Kuester, Jackson, and Runyan received consulting fees from AveXis during the conduct of this study. Pezalla and Nussbaum received consulting fees from Milliman during the conduct of this study. Nussbaum reports consulting fees from Sarepta Therapeutics and Ultragenyx Pharmaceutical outside of this study and serves on the Commercial Advisory Board of Gilead Sciences. A variation on this topic was presented at the Academy of Managed Care Pharmacy Nexus 2018; October 22-25, 2018; Orlando, FL.

Tech news: stem cells for modeling and curing disease.

Freya Leask explores developments in cell culture and stem cell research that are revolutionizing how diseases are studied and treated.

Regenerative Medicine Venturing at the University-Industry Boundary: Implications for Institutions, Entrepreneurs, and Industry.

Regenerative medicine research at university laboratories has outpaced commercial activity. Legal, regulatory, funding, technological, and operational uncertainty have slowed market entry of regenerative medicine treatments. As a result, commercial development has often been led by entrepreneurial ventures rather than large biopharma firms. Translating regenerative medicine across the university-industry boundary links academic scientists, technology transfer organizations, funders, and entrepreneurs. Conflicting motivations among the participants may significantly hinder these efforts. Unproven downstream business models for regenerative medicine delivery further complicate the entrepreneurial process. This chapter explores the challenges associated with entrepreneurial activity commercializing regenerative medicine science developed at research institutions.

Can Regenerative Medicine Help Close the Gap Between the Medicine Pipeline and Public Health Burden of Cardiovascular and Musculoskeletal Diseases?

PURPOSE: This commentary discusses the therapeutic and economic potentials of regenerative medicine (RM) by addressing how the reprioritization of resources in drug development may alleviate unmet medical need across many diseases, but especially cardiovascular diseases (CVDs) and musculoskeletal diseases (MSDs), the leading causes of mortality and morbidity, respectively, in the United States. METHODS: Data and perspectives represented in this commentary were obtained through an online literature search, public press releases from federal agencies and companies, online opinion pieces, published journal articles, and consulting agency reports; however, there were limitations to the available data because of the breadth and novelty of the therapeutic modalities involved. FINDINGS: Currently, the misallocation of resources within the therapeutic areas of CVDs and MSDs are possibly contributing to low approval rates, high cost of drug treatments, and consequently, disease burden. With a 2025 global market estimate of US $50.5 billion, RM is expected to become a major player in the pharmaceutical industry, with a potential to change the treatment paradigm and lessen disease burden across multiple disease areas, most notably in CVDs and MSDs. IMPLICATIONS: While the public sector appears to be doing its fair share by funding basic research and revamping regulatory regimes to address the vagaries of RM as a rapidly emerging novel technology, the support framework necessary for transforming the field from a promising concept to available therapy requires levels of resource allocation and marketing support that only the private sector can provide.

Cell therapy-processing economics: small-scale microfactories as a stepping stone toward large-scale macrofactories.

AIM: Manufacturing methods for cell-based therapies differ markedly from those established for noncellular pharmaceuticals and biologics. Attempts to 'shoehorn' these into existing frameworks have yielded poor outcomes. Some excellent clinical results have been realized, yet emergence of a 'blockbuster' cell-based therapy has so far proved elusive. MATERIALS & METHODS: The pressure to provide these innovative therapies, even at a smaller scale, remains. In this process, economics research paper, we utilize cell expansion research data combined with operational cost modeling in a case study to demonstrate the alternative ways in which a novel mesenchymal stem cell-based therapy could be provided at small scale. RESULTS & CONCLUSIONS: This research outlines the feasibility of cell microfactories but highlighted that there is a strong pressure to automate processes and split the quality control cost-burden over larger production batches. The study explores one potential paradigm of cell-based therapy provisioning as a potential exemplar on which to base manufacturing strategy.

Distributive justice and regenerative medicine.

Many countries have identified regenerative medicine as a strategic priority, and have thus launched a range of initiatives to facilitate innovation in the field. This perspective paper argues that several initiatives involve resource distributions that could impinge on widely accepted egalitarian notions of fairness and justice that underpin current healthcare systems. Specifically, this paper focuses on five initiatives, and argues that these initiatives reflect a largely unacknowledged utilitarian perspective on distributive justice. The intention of this paper is not to argue against these initiatives, but rather to stimulate an open discussion on what qualifies as a just and fair system of resource distribution, so that the regenerative medicine field can responsibly deliver on its clinical potential.