Overcoming regulatory and economic challenges facing pharmacogenomics.

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist.

FDA review divisions: performance levels and the impact on drug sponsors.

Sponsors of new drug applications (NDAs) confront a host of uncertainties, one of the more vexing of which is negotiating the differing and inconsistent policies and standards among the various US Food and Drug Administration (FDA) drug review divisions. The FDA faces many challenges as well, internal and external, that confound its efforts to provide a consistent and timely review process. In this article, we examine various input factors, such as the number of regulatory filings, that contribute to fluctuations in the annual FDA workload, as well as output factors, such as NDA approval times, that are often viewed by sponsors as measures of the FDA's performance.

Clinical and economic challenges facing pharmacogenomics.

In this paper, we examine the clinical and economic challenges that face developers of and payers for personalized drugs and companion diagnostics. We review and summarize clinical, regulatory and reimbursement issues with respect to eight, high profile personalized medicines and their companion diagnostics. Subsequently, we determine Medicare parts B and D reimbursement of the eight drugs from publicly available databases.

Patient access to new cancer drugs in the United States and Australia.

Objectives: In light of the current debate on the use value and potential impact of comparative effectiveness research on patient access, it may prove insightful to compare a health-care system that systematically bases its reimbursement decisions on comparative effectiveness evidence with the United States (US) system that hitherto has only been informed by such evidence on an ad hoc basis.

Methods: For a set of 2000-2009 approved new molecular entities and biologics indicated for cancer, we compared patient access between US Medicare and Australian Pharmaceutical Benefits Scheme (PBS) beneficiaries. Here, access is defined in terms of marketing availability, payer coverage, and patient out-of-pocket costs.

Biopharmaceutical industry perspectives on the business prospects for personalized medicine.

Aim: Personalized medicine is entering its second decade, yet the role it will play in addressing the biopharmaceutical industry's productivity gap and the rising cost of healthcare is still a matter of speculation. So what does the biopharmaceutical industry itself say about the business prospects for personalized medicine?

Materials & Methods: The authors conducted interviews with 20 science and business experts from 13 companies to find out. In this article, particular attention is paid to drug-diagnostic codevelopment, so-called companion diagnostics.

A New Mechanism for Tracking Publicly Available Study Volunteer Demographics.

The importance of gathering and monitoring aggregate demographic data on the annual population of study volunteers in FDA-regulated clinical trials is widely acknowledged. To date, no formal mechanism exists to capture this information. The Tufts Center for the Study of Drug Development identified and tested a publicly available source of information on clinical trial participant data, NDA Reviews stored in the FDA's drugs@FDA database, to determine its accuracy, reliability, and feasibility.

FDA's risk evaluation and mitigation strategies (REMS): effective and efficient safety tools or process poltergeist?

Implementation of REMS began in March 2008 and by mid-2011 close to 200 New Molecular Entities (NMEs) and New Drug Applications (NDAs) (i.e., NMEs plus new doses and formulations of drugs) approved by FDA were required to have a REMS.

Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000-2009.

The first decade of the 21st century was a challenging period for the pharma sector and could prove to be a turning point in the evolution of the industry. We examine drug development performance metrics for new product approvals during 2000-2009 and compare them with those of the prior two decades. The results indicate that, whereas total approvals are currently at a 25-year low, the percentage of priority products is nearly 50% of the total--a 30-year high.

Competitiveness in follow-on drug R&D: a race or imitation?

The development of 'follow on' or 'me too' drugs - generally defined as a drug with a similar chemical structure or the same mechanism of action as a drug that is already marketed - has attracted contrasting views. Some have argued that follow-on drugs often provide useful alternative or enhanced therapeutic options for particular patients or patient subpopulations, as well as introducing price competition. Others, however, consider that the development of such drugs is duplicative and that the resources needed would be better directed elsewhere.

Antibody-based therapeutics to watch in 2011.

This overview of 25 monoclonal antibody (mAb) and 5 Fc fusion protein therapeutics provides brief descriptions of the candidates, recently published clinical study results and on-going Phase 3 studies. In alphanumeric order, the 2011 therapeutic antibodies to watch list comprises AIN-457, bapineuzumab, brentuximab vedotin, briakinumab, dalotuzumab, epratuzumab, farletuzumab, girentuximab (WX-G250), naptumomab estafenatox, necitumumab, obinutuzumab, otelixizumab, pagibaximab, pertuzumab, ramucirumab, REGN88, reslizumab, solanezumab, T1h , teplizumab, trastuzumab emtansine, tremelimumab, vedolizumab, zalutumumab and zanolimumab. In alphanumeric order, the 2011 Fc fusion protein therapeutics to watch list comprises aflibercept, AMG-386, atacicept, Factor VIII and Factor IX-Fc.

Impact of the new US health-care-reform legislation on the pharmaceutical industry: who are the real winners?

Over the past two years, the US pharmaceutical and biotechnology industries were preparing themselves for passage of some type of health-reform legislation with a clear appreciation-and concern-about the enormous impact any law would be likely to have on the structure and viability of the research-based industry. Now, with final passage in March 2010 of the Patient Protection and Affordable Care Act and its companion "quick-fix" and budget bill, the Health Care and Education Reconciliation Act, it is a good time to take a look at how the industry fared and assess how the various provisions of the health-care reform bill might affect the industry's long-term prosperity and growth.

Translational medicine: an engine of change for bringing new technology to community health.

Bringing a new medical technology from the lab to the clinic is a daunting prospect, but making sure that same innovation is available to the average patient has proven to be even more challenging. Translational medicine is a movement intended to help bench researchers and bedside clinicians learn from each other for the benefit of patients. This goal can best be accomplished if a patient-centered focus is incorporated throughout the R&D continuum and changes are made so that biomedical innovation serves the broadest needs within the shortest period of time.

Trends in risks associated with new drug development: success rates for investigational drugs.

This study utilizes both public and private data sources to estimate clinical phase transition and clinical approval probabilities for drugs in the development pipelines of the 50 largest pharmaceutical firms (by sales). The study examined the development histories of these investigational compounds from the time point at which they first entered clinical testing (1993-2004) through June 2009. The clinical approval success rate in the United States was 16% for self-originated drugs (originating from the pharmaceutical company itself) during both the 1993-1998 and the 1999-2004 subperiods.

Deconstructing the drug development process: the new face of innovation.

Forged in the early 1960s, the paradigm for pharmaceutical innovation has remained virtually unchanged for nearly 50 years. During a period when most other research-based industries have made frequent and often sweeping modifications to their R&D processes, the pharmaceutical sector continues to utilize a drug development process that is slow, inefficient, risky, and expensive. Few who work in or follow the activities of the pharmaceutical industry question whether change is coming.

European Medicines Agency workshop on biosimilar monoclonal antibodies: July 2, 2009, London, UK.

The European Medicines Agency (EMEA) workshop on biosimilar monoclonal antibodies (mAbs), held July 2, 2009 at the EMEA headquarters in London, was a harbinger with potentially far-reaching implications for all groups interested in antibody therapeutics development. These groups include not only regulators and the innovator and generic biopharmaceutical industries, but also physicians, patients and payers. The objective of the workshop was to discuss and assess the feasibility of the development and authorization of mAbs using EMEA's biosimilar regulatory pathways.

Antibodies to watch in 2010.

Monoclonal antibodies (mAbs) are a burgeoning class of therapeutics, with more than 25 approved in countries worldwide. Novel molecules are entering clinical study at a rate of nearly 40 per year, and the commercial pipeline includes approximately 240 mAb therapeutics in clinical studies that have not yet progressed to regulatory approval or been approved. Of particular interest are the 26 mAbs that are currently at Phase 3, when safety and efficacy data critical to approval is established.

Second International Conference on Accelerating Biopharmaceutical Development: March 9-12, 2009, Coronado, CA USA.

The Second International Conference on Accelerating Biopharmaceutical Development was held in Coronado, California. The meeting was organized by the Society for Biological Engineering (SBE) and the American Institute of Chemical Engineers (AIChE); SBE is a technological community of the AIChE. Bob Adamson (Wyeth) and Chuck Goochee (Centocor) were co-chairs of the event, which had the theme "Delivering cost-effective, robust processes and methods quickly and efficiently.

New challenges to medicare beneficiary access to mAbs.

Precision binding of monoclonal antibodies (mAbs) to biological targets, their relative clinical success, and expansion of indications following initial approval, are distinctive clinical features. The relatively high cost of mAbs, together with the absence of a regulatory pathway to generics, stand out as distinctive economic features. Based on both literature review and primary data collection we enumerated mAb original approvals, supplemental indications and off-label uses, assessed payer formulary management of mAbs, and determined new challenges to Medicare beneficiary access to mAbs.

Off-label use reimbursement.

In this study, the authors examine factors underlying payer off-label use reimbursement policies. Updating a study published 14 years ago, presenting the results of the survey of 179 payers administering public (Medicare and Medicaid) pharmacy benefits. The focus is on payers administering pharmacy benefits in the public sector for two reasons: First, transparency; there is a tendency for such payers to reveal more about their decisionmaking processes than payers that exclusively deal with the commercial market.

Can translational medicine bring us out of the R&D wilderness?

After 50 years of wandering among new discovery technologies and a worrying antiquated development process, the research and development (R&D) enterprise may finally have found a way out of its wilderness through the auspices of translational medicine. For that to happen, a number of problems have to be confronted. Most prominent is the traditional problem credited with giving rise to translational medicine - the lack of a feedback loop from bench to bedside.