Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 2017
ReviewFirst-in-Class Composite Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in Practice.
Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) inhibits angiotensin II and neprilysin, enhancing circulating vasoactive peptides. It is recommended in heart failure with reduced ejection fraction (HFrEF) as a result of the PARADIGM-HF trial.1 This review discusses the rationale for neprilysin inhibition, data supporting efficacy, and practical tips for patient selection and utilization.
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Clin. Pharmacol. Ther. · Aug 2017
ReviewOcclusion in the Flow of New Drugs for Cardiovascular Disease.
There is a large misalignment between unmet need and both private and public investment activity in cardiovascular disease. In this paper, we quantify the magnitude of the gap, analyze a range of potential root causes in two main categories (issues of feasibility and valuation), and propose steps toward solutions to close the gap.
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Clin. Pharmacol. Ther. · Aug 2017
ReviewPluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing.
The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing.
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Clin. Pharmacol. Ther. · Aug 2017
LetterRegulatory Consequences of "Brexit" for the Development of Medicinal Products.
The United Kingdom voted in a referendum in June 2016 to leave the European Union (EU) after 45 years of membership. Among the many political, social, and scientific consequences are those for the regulation of health care products. ⋯ The European Medicines Agency (EMA), which is currently located in London, will move elsewhere in Europe. The pharmaceutical industry will reassess its commitment to the UK health scene.
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Clin. Pharmacol. Ther. · May 2017
ReviewDrug Development, Trial Design, and Endpoints in Oncology: Adapting to Rapidly Changing Science.
As a result of enhanced understanding of genetic and immunologic underpinnings of cancer, there has been progress in development of targeted and immunotherapies in oncology. The traditional linear sequential model of drug development has evolved. Early clinical trials of breakthrough therapies often include expansion cohorts, termed "seamless drug development." The US Food and Drug Administration (FDA) uses expedited programs, such as breakthrough designation and accelerated approval ensuring that transformative therapies are available to patients earlier in the cycle of evidence generation.