Publications by authors named "W Jeffrey Hurst"

128 Publications

Structured benefit-risk evaluation for medicinal products: review of quantitative benefit-risk assessment findings in the literature.

Ther Adv Drug Saf 2020 8;11:2042098620976951. Epub 2020 Dec 8.

Global Epidemiology & Benefit-Risk Evaluation, Sanofi, Chilly-Mazarin, France.

A favorable benefit-risk profile remains an essential requirement for marketing authorization of medicinal drugs and devices. Furthermore, prior subjective, implicit and inconsistent ad hoc benefit-risk assessment methods have rightly evolved towards more systematic, explicit or "structured" approaches. Contemporary structured benefit-risk evaluation aims at providing an objective assessment of the benefit-risk profile of medicinal products and a higher transparency for decision making purposes. The use of a descriptive framework should be the preferred starting point for a structured benefit-risk assessment. In support of more precise assessments, quantitative and semi-quantitative methodologies have been developed and utilized to complement descriptive or qualitative frameworks in order to facilitate the structured evaluation of the benefit-risk profile of medicinal products. In addition, quantitative structured benefit-risk analysis allows integration of patient preference data. Collecting patient perspectives throughout the medical product development process has become increasingly important and key to the regulatory decision-making process. Both industry and regulatory authorities increasingly rely on descriptive structured benefit-risk evaluation and frameworks in drug, vaccine and device evaluation and comparison. Although varied qualitative methods are more commonplace, quantitative approaches have recently been emphasized. However, it is unclear how frequently these quantitative frameworks have been used by pharmaceutical companies to support submission dossiers for drug approvals or to respond to the health authorities' requests. The objective of this study has been to identify and review, for the first time, currently available, published, structured, quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.

Plain Language Summary: The review of the benefits and the risks associated with a medicinal product is called benefit-risk assessment. One of the conditions for a medicinal product to receive marketing authorization is to demonstrate a positive benefit-risk balance in which the benefits outweigh the risks. In order to enhance the transparency and consistency in the assessment of benefit-risk balance, frameworks and quantitative methods have been developed for decision making purposes and regulatory approvals of medicinal products. This article considers published quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.
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http://dx.doi.org/10.1177/2042098620976951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727082PMC
December 2020

Isolation of 1-(3',4'-Dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol from Grape Seed Extract and Evaluation of its Antioxidant and Antispasmodic Potential.

Molecules 2019 Jul 4;24(13). Epub 2019 Jul 4.

Planta Analytica LLC, New Milford, CT 06776, USA.

HPLC profiling of phenolics in grape seed extracts revealed a prominent peak of an unknown substance with concentrations up to 5.3%. Spectroscopic data allowed the identification of the compound as 1-(3',4'-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol. is known to be produced from catechin and epicatechin through anaerobic bacteria from human, as well as the rat, intestines. It was hypothesized that the marc remaining after expression of juice from grapes became infested during storage, resulting in the production of . Because compound is infrequently found in nature and has never been found in grape seeds, its presence may be considered a marker of an unwanted anaerobic bacterial process occurring during production. The antioxidant potential of was determined by DPPH, ABTS, and FRAP (ferric reducing antioxidant power) assays and compared to the potential of the following compounds: phloroglucine, pyrogallol, gallic acid, catechin, and epicatechin. Furthermore, it was established that significantly reduced guinea pig ileum contraction induced by histamine.
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http://dx.doi.org/10.3390/molecules24132466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651082PMC
July 2019

Impact of lixisenatide dose range on clinical outcomes with fixed-ratio combination iGlarLixi in patients with type 2 diabetes.

Curr Med Res Opin 2019 04 6;35(4):689-695. Epub 2018 Dec 6.

d Abington Family Medicine , Jenkintown , PA , USA.

Objective: To evaluate the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen (5-20 µg), alone or in fixed-ratio combination with insulin glargine (iGlar; iGlarLixi).

Methods: Data from three clinical studies were analyzed to assess lixisenatide efficacy and safety: a phase 2a trial assessing gastric emptying effects (ACT6011); a phase 2b dose-ranging trial (DRI6012); and a randomized controlled phase 3 trial comparing iGlarLixi with its components of iGlar and lixisenatide (LixiLan-O). Efficacy metrics included glycated hemoglobin A (A1C), post-prandial glucose (PPG) values following a standardized breakfast, fasting plasma glucose (FPG), and weight change. Occurrence of gastrointestinal adverse events was also assessed.

Results: ACT6011: lixisenatide doses from 5-20 μg once daily (QD) suppressed PPG; maximal reductions in mean PPG area under the curve were achieved with doses ≥12.5 µg QD, but doses as low as 5 μg achieved 44% of maximal reduction. DRI6012: lixisenatide doses 5-20 μg QD resulted in significant, dose-dependent decreases in A1C, percentage of patients achieving A1C <7.0%, and 2-h PPG levels; doses of 20 μg achieved complete suppression of PPG. LixiLan-O: iGlarLixi decreased 2-h PPG across the entire dose range. Lixisenatide dose was unrelated to reductions in FPG with iGlarLixi. Similar reductions in A1C were seen with iGlarLixi across all lixisenatide doses.

Conclusions: This analysis demonstrates the clinical benefit of lixisenatide alone or in the formulation of iGlarLixi over the entire dose range of lixisenatide contained in iGlarLixi (5-20 µg), supporting the selection of the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen.
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http://dx.doi.org/10.1080/03007995.2018.1541316DOI Listing
April 2019

Fifteen-year longitudinal follow-up of a patient with severe early-onset Charcot-Marie-Tooth disease type 2A.

Muscle Nerve 2018 05 26;57(5):E126-E128. Epub 2018 Jan 26.

Department of Neurology, Johns Hopkins University School of Medicine, John G. Rangos Building, 855 North Wolfe Street, Suite 227 Baltimore, Maryland, 21205, USA.

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http://dx.doi.org/10.1002/mus.26047DOI Listing
May 2018

Positron Emission Tomography Assessment of the Intranasal Delivery Route for Orexin A.

ACS Chem Neurosci 2018 02 7;9(2):358-368. Epub 2017 Nov 7.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.

Intranasal drug delivery is a noninvasive drug delivery route that can enhance systemic delivery of therapeutics with poor oral bioavailability by exploiting the rich microvasculature within the nasal cavity. The intranasal delivery route has also been targeted as a method for improved brain uptake of neurotherapeutics, with a goal of harnessing putative, direct nose-to-brain pathways. Studies in rodents, nonhuman primates, and humans have pointed to the efficacy of intranasally delivered neurotherapeutics, while radiolabeling studies have analyzed brain uptake following intranasal administration. In the present study, we employed carbon-11 radioactive methylation to assess the pharmacokinetic mechanism of intranasal delivery of Orexin A, a native neuropeptide and prospective antinarcoleptic drug that binds the orexin receptor 1. Using physicochemical and pharmacological analysis, we identified the methylation sites and confirmed the structure and function of methylated Orexin A (CH-Orexin A) prior to monitoring its brain uptake following intranasal administration in rodent and nonhuman primate. Through positron emission tomography (PET) imaging of [C]CH-Orexin A, we determined that the brain exposure to Orexin A is poor after intranasal administration. Additional ex vivo analysis of brain uptake using [I]Orexin A indicated intranasal administration of Orexin A affords similar brain uptake when compared to intravenous administration across most brain regions, with possible increased brain uptake localized to the olfactory bulbs.
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http://dx.doi.org/10.1021/acschemneuro.7b00357DOI Listing
February 2018
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