Search

Durable cell and gene therapies potentially transform patient lives, but payers fear unsustainable costs arising from the more than 1000 therapies in the development pipeline. A novel multi-module Markov chain Monte Carlo-based model projects product-indication approvals, treated patients, and product revenues. We estimate a mean 63.5 (54-74 5th to 95th percentile range) cumulative US product-indication approvals through 2030, with a mean 93000 patients treated in 2030 generating a mean US$24.4 billion (US$17.0B-35.0B, US$73.0B extreme) list price product revenues not including ancillary medical costs or cost offsets. Thus, the likely dozens of durable cell and gene therapies developed through 2030 are unlikely to threaten US health system financial sustainability.

April 2019 was perhaps remarkable for the amount of industry news about gene therapy, and notably the announcement by a global contract development and manufacturing organization, Catalent, that it was creating a capability in gene therapy product development and manufacturing through its acquisition of Paragon Bioservices, Inc (MD, USA). This move followed just a few weeks after another similar major contract development and manufacturing organization gene therapy acquisition. There was other encouraging gene and cell therapy news reported from AveXis (IL, USA), Ajinomoto Bio-Pharma (CA, USA), Kiadis Pharma (Amsterdam, The Netherlands), Fibrocell (PA, USA), Autolus Therapeutics plc (London, UK), ReNeuron (Surrey, England) and Kite Pharma (CA, USA). Also, there was plenty of therapeutic delivery technology innovation announced, including Calixar’s (Lyon, France) membrane protein stabilization drug discovery technology, the Eli Lilly (IN, USA)/Avidity Biosciences LLC (CA, USA) deal around antibody oligonucleotide conjugates, ViiV Healthcare’s regulatory filing for its long-acting anti-HIV-1 intramuscular injection, Marinomed Biotech’s (Vienna, Austria) solubilization technology and an EU approval filing for Novo Nordisk’s (Bagsværd, Denmark) oral delivery formulation of glucagon-like peptide-1 analog semaglutide. Diseases and treatment approaches that currently figure strongly in many biotech and big pharma pipelines and portfolios, notably nonalcoholic steatohepatitis and immuno-oncology, were as ever in the news, along with a number of rare disease therapies. As always, information sources employed to provide the materials used in compiling this update included company press releases, conference news and other news websites.

1–31 December 2018, the period covered by this article, was again a very interesting period for activity under the therapeutic delivery umbrella, being a particularly solid month for business activity, notably a major acquisition by GSK to expand its oncology portfolio. This was, as it later turns out, the first of several very significant mergers and acquisitions around the turn of the year in the oncology area, more of which will appear in future articles. In that acquisition, the acquisition of Potenza Therapeutics (MA, USA) by Astellas Pharma Inc. (Tokyo, Japan), Amgen's (CA, USA) collaboration with Molecular Partners (Zurich, Switzerland), the partnership between Domain Therapeutics (Strasbourg, France) and Boehringer Ingelheim (Ingelheim am Rhein, Germany), and the deal between Argenx (Breda, The Netherlands) and Cilag GmbH International (Zug, Switzerland), all announced in the month, demonstrated the high continued interest within industry around the development of immuno-oncology therapeutics. Additionally, activity around therapeutic delivery technologies was prominent in the news, for example the Amgen/Entera Bio (Jerusalem, Israel) deal around oral delivery of large molecules, Entrada Therapeutic's (MA, USA) successful acquisition of funding to advance its work on intracellular delivery of biologics, Impel NeuroPharma's (WA, USA) securing of support continue its development of its nose-to-brain delivery pipeline, US FDA approval of inhaled levodopa from Acorda Therapeutics Inc. (NY, USA) and a sublingual delivery technology for dexmedetomidine under development by BioXcel Therapeutics (CT, USA) being advanced into clinical evaluation were just some of the items noted. As always, information sources employed to provide the materials used in compiling this update included company press releases, conference news and other news websites.

Slow uptake of biosimilars in some regions is often attributed to a lack of knowledge combined with concerns about safety and efficacy. To alleviate physician and patient apprehensions, regulatory reviews from four major regulatory authorities (RAs) (European Medicines Agency, US Food and Drug Administration, Health Canada, and Japan Pharmaceuticals and Medical Devices Authority) across a portfolio of eight biosimilars were analyzed to provide insight into RA review focus and approach. RA queries were evaluated in an unbiased and systematic manner by major classification (Chemistry, Manufacturing and Controls [CMC], nonclinical, clinical or regulatory) and then via detailed sub-classification. There was a consistent, predominant focus on CMC from all RAs. The review focus based on sub-classification of clinical and regulatory queries was influenced by molecular complexity, with significant differences between categories (monoclonal antibody or protein) in the distribution of query topics, specifically, bioanalytical (p = 0.023), comparative safety and efficacy (p = 0.023), and statutory (including the justification of extrapolation) (p = 0.00033). Each biosimilar had a distinct distribution of clinical query topics, tailored to product-specific data. This analysis elucidated areas of heightened RA interest, and validated their application of regulatory science in the evaluation of biosimilar safety and efficacy.

Objective Under the circumstances that several oncology drugs have been approved under expedited programs in the US, this study aimed to analyze the relationship between the expedited programs and characteristics of approvals in the recent decade, and the attitude of the Food and Drug Administration (FDA) toward the development and review of oncology drugs. Results Of the 162 approvals that were analyzed, the proportion of orphan drug (OD) designation was higher in accelerated approval (AA) than regular approval (RA). In contrast, no difference was observed in the proportions of priority review (PR) in AA versus RA or in ODs versus non-ODs. In the development time, no difference was observed in any of the expedited programs. Regarding review time, a significant difference was observed in PR versus standard review (SR). In the characteristics of the pivotal study, such as randomization, number of patients, and endpoints, differences were observed in AA versus RA and in ODs versus non-ODs. Conversely, no significant difference was noted in PR versus SR. Conclusion The overall results of this research validated the attitude of the FDA toward applying each expedited program to facilitate an earlier delivery of innovative oncology drug products to patients with cancer.

The baculovirus expression vector system (BEVS) platform has become an established manufacturing platform for the production of viral vaccines and gene therapy vectors. Nine BEVS‐derived products have been approved – four for human use (Cervarix®, Provenge®, Glybera® and Flublok®) and five for veterinary use (Porcilis® Pesti, BAYOVAC CSF E2®, Circumvent® PCV, Ingelvac CircoFLEX® and Porcilis® PCV). The BEVS platform offers many advantages, including manufacturing speed, flexible product design, inherent safety and scalability. This combination of features and product approvals has previously attracted interest from academic researchers, and more recently from industry leaders, to utilize BEVS to develop next generation vaccines, vectors for gene therapy, and other biopharmaceutical complex proteins. In this review, we explore the BEVS platform, detailing how it works, platform features and limitations and important considerations for manufacturing and regulatory approval. To underscore the growth in opportunities for BEVS‐derived products, we discuss the latest product developments in the gene therapy and influenza vaccine fields that follow in the wake of the recent product approvals of Glybera® and Flublok®, respectively. We anticipate that the utility of the platform will expand even further as new BEVS‐derived products attain licensure. Finally, we touch on some of the areas where new BEVS‐derived products are likely to emerge., The baculovirus expression vector system (BEVS) has become an established commercial manufacturing platform. The authors review this technology, which enables fast, flexible and scalable protein production and is increasingly being used for the production of viral vaccines and gene therapy vectors. Nine BEVS‐derived products have been licensed by global regulatory authorities, paving the way for new products that are in development. WILEY‐VCH

The twin forces of payors seeking fair pricing and the rising costs of developing new medicines has driven a closer relationship between pharmaceutical companies and diagnostics companies, because stratified medicines, guided by companion diagnostics, offer better commercial, as well as clinical, outcomes. Stratified medicines have created clinical success and provided rapid product approvals, particularly in oncology, and indeed have changed the dynamic between drug and diagnostic developers. The commercial payback for such partnerships offered by stratified medicines has been less well articulated, but this has shifted as the benefits in risk management, pricing and value creation for all stakeholders become clearer. In this larger healthcare setting, stratified medicine provides both physicians and patients with greater insight on the disease and provides rationale for providers to understand cost-effectiveness of treatment. This article considers how the economic value of stratified medicine relationships can be recognized and translated into better outcomes for all healthcare stakeholders.

New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development.

In 2006, the US Food and Drug Administration (FDA) published draft guidance to provide recommendations for development, validation, implementation, and interpretation of patient-reported outcome (PRO) measures that can support treatment benefit claims in product labeling. Here, we summarize and discuss FDA approvals of anticancer products in the context of the draft guidance. We identified anticancer product approvals having efficacy claim(s) based at least in part on a PRO. In addition, we collated limitations of PRO instruments commonly submitted for regulatory review over the period from October 1, 2004 to September 30, 2006. From 1995 onward, nine indications were approved for seven anticancer products based at least in part on a PRO. In eight of nine approvals, PRO data supplemented other evidence of clinical benefit. In seven approvals, the PRO measured a single symptom or functional domain that was directly attributable to the treatment benefit observed in the disease. The FDA's draft PRO guidance describes principles that have been used in anticancer product approvals for more than a decade. PRO end points typically support treatment benefit claims that refer to a patient's symptoms or ability to function. Single-item PROs may be acceptable. PRO data should be both internally consistent and aligned with other evidence of clinical benefit. The FDA encourages sponsors to consult with the FDA early in the process of PRO development.

Biotechnology firms face new challenges as biologics account for an increasing share of product approvals and pipelines and their high costs are under scrutiny by regulators, employers, and consumers. Although the first generation of biologics often targeted niche markets with little impact on payers' total costs, the current product wave addresses larger populations. To meet the needs of all stakeholders, manufacturers must adopt an evidence-based approach including three principles: demonstration of clinical and economic value, price evolution according to market conditions (from orphan diseases to large areas such as diabetes), and an early timetable integrating clinical and economic endpoints.

This article has outlined only a small example of product safety standards, but the message is that product approvals are complicated and exist for a good reason. Believing they are quick and simple has all too often proved be short-sighted and expensive, so it is worth having or hiring an experienced set of eyes to review the project before it is completed ideally at the start of a project, or before the product is submitted for approvals testing. Approvals bring kudos and demonstrate a level of competence, plus diligence on the part of the business.

Government regulations are an increasingly important component of the environment in which firms operate. Regulations may subject firms to large costs and possibly regulatory-induced risks, both of which may have effects on stockholders' wealth. In this paper we investigate the valuation effects of Food and Drug Administration (FDA) product approvals, rejections and disciplinary decisions on the firms that operate in the food and drug industries. We find that FDA decisions have very large wealth effects. The large price changes associated with approval and rejection decisions suggest that a significant amount of uncertainty about FDA decisions is present almost up to the announcement day. These results are somewhat surprising given the lengthy period of time involved in developing and reviewing drugs and the continuous flow of information received by the market about their potential. We also find some evidence of information leaks preceding FDA announcements. With respect to disciplinary decisions, the evidence from the data suggests that stockholders experience large losses associated with FDA actions. Since these losses represent lost stream of future illegal income, it appears that ignoring FDA rules may be quite profitable for firms that are not caught.

Drugs remain a key element in the effective containment of health care costs. In 1993, 29 new drugs were approved for marketing by the US Food and Drug Administration (FDA). These entities, according to a 1993 Office of Technology Assessment study, each took on average 12 years and $359 million each to discover and develop. The FDA reported that the average review time for these entities was 26.5 months, some 3 months less than reported in 1992. Under the prescription Drug User Fee Act of 1992, which will generate an additional $327 million over the period 1993–1997, the FDA will hire an additional 600 review staff.

Regulatory and financial challenges conspire to stall the development and market approval of breakthrough medical products. Inconsistent parameters are used to assess the safety and efficacy of drugs, biologics, and devices; this glitch in the system introduces uncertainty, slows or blocks product approvals, and increases the costs of product development. Here, we consider how to balance the benefits and risks to the public in the assessment of innovative medical products. We also discuss the Institute of Medicine's recent report on the medical device approval process.

FDA in 2008 approved the marketing of an assortment of 34 unique new molecular entities, vaccines, imaging agents, and blood products—5 more than the previous year’s total. A brief synopsis of several product approvals is provided below. A full listing of products approved in 2008 and their