Use of Real-World Evidence Expands to Transform Drug Development
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Telaprevir (Incivek)
© Hepatitis C Online PDF created September 25, 2021, 4:19 pm Telaprevir (Incivek) Discontinued. This treatment has been discontinued. Table of Contents Telaprevir Incivek Summary Drug Summary Adverse Effects Class and Mechanism Manufacturer for United States FDA Status Indications Dosing Clinical Use Cost and Medication Access Resistance Key Drug Interactions Full Prescribing Information Figures Drug Summary Although telaprevir was a promising direct-acting antiviral agent that had impact in the hepatitis C treatment field during 2011 to 2013, it was subsequently replaced by newer direct-acting antiviral agents that were more effective, better tolerated, and more convenient. Based on the dwindling role of telaprevir after newer direct-acting antiviral agents were approved, Vertex pharmaceuticals discontinued the sales and distribution of telaprevir in the United States in October 2014. Telaprevir does have some current importance since persons who previously failed a telaprevir-based regimen may have developed resistant associated variants, which could potentially impact subsequent therapy. Adverse Effects The most significant adverse effects reported in the main registration trials and in post-marketing experience were rash, anorectal complaints, and anemia. When comparing triple therapy of telaprevir, peginterferon, and ribavirin with dual therapy of peginterferon and ribavirin alone significant differences were noted with rash (56% versus 34%), anemia (36% versus 17%), and anorectal complaints that include anorectal discomfort, anal pruritus, and hemorrhoids (29% versus 7%). In most cases, the rash that develops is eczematous or maculopapular in character and mild to moderate in severity; the rash is typically manageable with good skin care and topical emollients or corticosteroids. In some instances, however, telaprevir has caused serious skin Page 1/5 rashes, including Steven's Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN). -
Meta Analyses – Pros and Cons
Meta analyses – pros and cons Emily S Sena, PhD Centre for Clinical Brain Sciences, University of Edinburgh @camarades_ CAMARADES: Bringing evidence to translational medicine CAMARADES • Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies • Look systematically across the modelling of a range of conditions • Data Repository – 30 Diseases – 40 Projects – 25,000 studies – from over 400,000 animals CAMARADES: Bringing evidence to translational medicine Why do we do meta-analysis of animal studies? • Animal models are generally performed to inform human health but when should you be convinced to move to the next step? • Systematic reviews & meta-analyses: – assess the quality and range of evidence – identify gaps in the field – quantify relative utility of outcome measures – inform power/sample size calculations – assess for publication bias – try to explain discrepancies between preclinical and clinical trial results – inform clinical trial design CAMARADES: Bringing evidence to translational medicine Systematic review and meta-analysis • Pros – What have we learnt about…….. • Translation? • Quality? • The 3Rs? • Cons – What are the limitations? • As good as the data that goes in? • Rapidly outdated • The Impact CAMARADES: Bringing evidence to translational medicine Systematic review and meta-analysis • Pros – What have we learnt about…….. • Translation? • Quality? • The 3Rs? • Cons – What are the limitations? • As good as the data that goes in? • Rapidly outdated • The Impact CAMARADES: Bringing evidence -
Melanoma: Epidemiology, Risk Factors, Pathogenesis, Diagnosis and Classification
in vivo 28: 1005-1012 (2014) Review Melanoma: Epidemiology, Risk Factors, Pathogenesis, Diagnosis and Classification MARCO RASTRELLI1, SAVERIA TROPEA1, CARLO RICCARDO ROSSI2 and MAURO ALAIBAC3 1Melanoma and Sarcoma Unit, Veneto Institute of Oncology, IOV- IRCCS, Padova, Italy; 2Melanoma and Sarcoma Unit, Veneto Institute of Oncology, IOV-IRCCS and Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; 3Dermatology Unit, University of Padova, Padova, Italy Abstract. This article reviews epidemiology, risk factors, Epidemiology pathogenesis and diagnosis of melanoma. Data on melanoma from the majority of countries show a rapid At the start of 21st century, melanoma remains a potentially increase of the incidence of this cancer, with a slowing of fatal malignancy. At a time when the incidence of many the rate of incidence in the period 1990-2000. Males are tumor types is decreasing, melanoma incidence continues to approximately 1.5-times more likely to develop melanoma increase (1). Although most patients have localized disease than females, while according to other studies, the different at the time of the diagnosis and are treated by surgical prevalence in both sexes must be analyzed in relation with excision of the primary tumor, many patients develop age: the incidence rate of melanoma is grater in women metastases (2). than men until they reach the age of 40 years, however, by The incidence of malignant melanoma has been increasing 75 years of age, the incidence is almost 3-times as high in worldwide, resulting in an important socio-economic men versus women. The most important and potentially problem. From being a rare cancer one century ago, the modifiable environmental risk factor for developing average lifetime risk for melanoma has now reached 1 in 50 malignant melanoma is the exposure to ultraviolet (UV) in many Western populations (3). -
ARK GENOMIC REVOLUTION MULTI SECTOR ETF (ARKG) HOLDINGS As of 09/27/2021
ARK GENOMIC REVOLUTION MULTI SECTOR ETF (ARKG) HOLDINGS As of 09/27/2021 Company Ticker CUSIP Shares Market Value($) Weight(%) 1 TELADOC HEALTH INC TDOC 87918A105 3,937,797 531,208,815.30 6.99 2 EXACT SCIENCES CORP EXAS 30063P105 3,971,013 381,296,668.26 5.01 3 PACIFIC BIOSCIENCES OF CALIF PACB 69404D108 13,696,148 350,347,465.84 4.61 4 VERTEX PHARMACEUTICALS INC VRTX 92532F100 1,722,281 316,228,014.41 4.16 5 FATE THERAPEUTICS INC FATE 31189P102 4,825,395 312,926,865.75 4.12 6 IONIS PHARMACEUTICALS INC IONS 462222100 8,572,965 310,341,333.00 4.08 7 REGENERON PHARMACEUTICALS REGN 75886F107 430,742 275,201,063.80 3.62 8 TWIST BIOSCIENCE CORP TWST 90184D100 2,237,350 250,829,308.50 3.30 9 TAKEDA PHARMACEUTIC-SP ADR TAK UN 874060205 13,592,076 229,570,163.64 3.02 10 ACCOLADE INC ACCD 00437E102 5,268,242 226,850,500.52 2.98 11 INTELLIA THERAPEUTICS INC NTLA 45826J105 1,508,421 224,965,907.94 2.96 12 VEEVA SYSTEMS INC-CLASS A VEEV 922475108 741,198 222,307,516.14 2.92 13 CAREDX INC CDNA 14167L103 3,433,475 220,978,451.00 2.91 14 CRISPR THERAPEUTICS AG CRSP H17182108 1,804,041 210,044,493.63 2.76 15 INCYTE CORP INCY 45337C102 2,893,385 199,643,565.00 2.63 16 INVITAE CORP NVTA 46185L103 6,059,066 182,135,523.96 2.40 17 ADAPTIVE BIOTECHNOLOGIES ADPT 00650F109 4,888,391 178,377,387.59 2.35 18 BEAM THERAPEUTICS INC BEAM 07373V105 1,849,698 175,110,909.66 2.30 19 SIGNIFY HEALTH INC -CLASS A SGFY 82671G100 8,107,683 160,937,507.55 2.12 20 UIPATH INC - CLASS A PATH 90364P105 2,955,628 155,761,595.60 2.05 21 CASTLE BIOSCIENCES INC CSTL 14843C105 2,130,211 -
Vertex Pharmaceuticals Global Medical Affairs Pharmd Fellowship Program 2020 Message from Global Medical Affairs Leadership
Vertex Pharmaceuticals Global Medical Affairs PharmD Fellowship Program 2020 Message from Global Medical Affairs Leadership Dear Candidates, Vertex Pharmaceuticals in collaboration with Northeastern University is privileged to host and expand the PharmD Fellowship Program. We are excited to work with our fellows as integral members of our team and facilitate in-depth exposure to a range of functional areas, offering them the critical opportunity to gain extensive experience in the biopharmaceutical industry. In addition to fostering each individual’s personal and professional growth, the program’s primary goal is to extend the visibility of valuable contributions that a Doctor of Pharmacy can bring to the pharmaceutical industry. At Vertex, our Global Medical Affairs fellows are highly encouraged to take on immersive projects, allowing them to work across departments with leaders in the industry. We advocate for them to partake in truly unique, impactful work that develops their skills, sparks curiosity, and drives the science. Vertex’s open and innovative culture allows the fellows to ask questions, challenge the status quo, and explore their interests across multiple expertise areas. As a pharmacist, I am extremely proud of the establishment of the Vertex PharmD Fellowship program in Global Medical Affairs and excited to welcome our future fellows. Vertex is an ideal place for fellows to start their professional career, and we are dedicated to the development of the next generation of pharmacist leaders in the biopharmaceutical industry. As Vertex continues to grow and evolve into a company in multiple disease areas, I am confident that our fellows will be an essential part of moving the needle to deliver on our commitment to patients. -
Adaptive Enrichment Designs in Clinical Trials
Annual Review of Statistics and Its Application Adaptive Enrichment Designs in Clinical Trials Peter F. Thall Department of Biostatistics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA; email: [email protected] Annu. Rev. Stat. Appl. 2021. 8:393–411 Keywords The Annual Review of Statistics and Its Application is adaptive signature design, Bayesian design, biomarker, clinical trial, group online at statistics.annualreviews.org sequential design, precision medicine, subset selection, targeted therapy, https://doi.org/10.1146/annurev-statistics-040720- variable selection 032818 Copyright © 2021 by Annual Reviews. Abstract All rights reserved Adaptive enrichment designs for clinical trials may include rules that use in- terim data to identify treatment-sensitive patient subgroups, select or com- pare treatments, or change entry criteria. A common setting is a trial to Annu. Rev. Stat. Appl. 2021.8:393-411. Downloaded from www.annualreviews.org compare a new biologically targeted agent to standard therapy. An enrich- ment design’s structure depends on its goals, how it accounts for patient heterogeneity and treatment effects, and practical constraints. This article Access provided by University of Texas - M.D. Anderson Cancer Center on 03/10/21. For personal use only. first covers basic concepts, including treatment-biomarker interaction, pre- cision medicine, selection bias, and sequentially adaptive decision making, and briefly describes some different types of enrichment. Numerical illus- trations are provided for qualitatively different cases involving treatment- biomarker interactions. Reviews are given of adaptive signature designs; a Bayesian design that uses a random partition to identify treatment-sensitive biomarker subgroups and assign treatments; and designs that enrich superior treatment sample sizes overall or within subgroups, make subgroup-specific decisions, or include outcome-adaptive randomization. -
Use of in Vivo and in Vitro Models to Guide Dose Selection for Neonatal Infections
Use of In Vivo and In Vitro Models to Guide Dose Selection for Neonatal Infections Professor William Hope Antimicrobial Pharmacodynamics & Therapeutics University of Liverpool September 2016 Disclosures • William Hope has received research funding from Pfizer, Gilead, Astellas, AiCuris, Amplyx, Spero Therapeutics and F2G, and acted as a consultant and/or given talks for Pfizer, Basilea, Astellas, F2G, Nordic Pharma, Medicines Company, Amplyx, Mayne Pharma, Spero Therapeutics, Auspherix, Cardeas and Pulmocide. First of all BIOMARKER OUTCOME OF CLINICAL DOSE INTEREST/IMPORTANCE •Decline in Log10CFU/mL •Linked to an outcome of clinical interest •Survival 7 6 5 4 CFU/g) CNS 10 3 Effect (log 2 1 0 0.01 0.1 1 10 100 1000 Total doseDose 5FC (mg/kg) PHARMACOKINETICS PHARMACODYNAMICS Concept of Expensive Failure COST Derisking White Powder Preclinical Program Clinical Program Concept from Trevor Mundell & Gates Foundation And this… Normal Therapeutics Drug A, Dose A1 versus Drug B, Dose B1 Pharmacodynamics is the Bedrock of ALL Therapeutics…it sits here without being seen One of the reasons simple scaling does not work is the fact pharmacodynamics are different Which means the conditions that govern exposure response relationships in neonates need to be carefully considered …Ignore these at your peril Summary of Preclinical Pharmacodynamic Studies for Neonates** • Hope el al JID 2008 – Micafungin for neonates – Primary question of HCME – Rabbit model with hematogenous dissemination • Warn et al AAC 2010 – Anidulafungin for neonates – Primary question -
Role and Limitations of Epidemiology in Establishing a Causal Association Eduardo L
Seminars in Cancer Biology 14 (2004) 413–426 Role and limitations of epidemiology in establishing a causal association Eduardo L. Franco a,∗, Pelayo Correa b, Regina M. Santella c, Xifeng Wu d, Steven N. Goodman e, Gloria M. Petersen f a Departments of Epidemiology and Oncology, McGill University, 546 Pine Avenue West, Montreal, QC, Canada H2W1S6 b Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, LA, USA c Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA d Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA e Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA f Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA Abstract Cancer risk assessment is one of the most visible and controversial endeavors of epidemiology. Epidemiologic approaches are among the most influential of all disciplines that inform policy decisions to reduce cancer risk. The adoption of epidemiologic reasoning to define causal criteria beyond the realm of mechanistic concepts of cause-effect relationships in disease etiology has placed greater reliance on controlled observations of cancer risk as a function of putative exposures in populations. The advent of molecular epidemiology further expanded the field to allow more accurate exposure assessment, improved understanding of intermediate endpoints, and enhanced risk prediction by incorporating the knowledge on genetic susceptibility. We examine herein the role and limitations of epidemiology as a discipline concerned with the identification of carcinogens in the physical, chemical, and biological environment. We reviewed two examples of the application of epidemiologic approaches to aid in the discovery of the causative factors of two very important malignant diseases worldwide, stomach and cervical cancers. -
United States Securities and Exchange Commission Form
UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 17, 2005 VERTEX PHARMACEUTICALS INCORPORATED (Exact name of registrant as specified in its charter) MASSACHUSETTS 000-19319 04-3039129 (State or other jurisdiction of (Commission File Number) (IRS Employer Identification incorporation) No.) 130 Waverly Street Cambridge, Massachusetts 02139 (Address of principal executive offices) (Zip Code) (617) 444-6100 Registrant’s telephone number, including area code: Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below): o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) Item 8.01. Other Events. On June 17, 2005, Vertex Pharmaceuticals Incorporated and Merck & Co., Inc. issued a joint press release that announced the initiation of an additional Phase I study with VX-680, a small molecule inhibitor of Aurora kinases. A copy of that press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference. Item 9.01. -
(GIVIMP) for the Development and Implementation of in Vitro Methods for 829 Regulatory Use in Human Safety Assessment
1 2 Draft GUIDANCE DOCUMENT ON GOOD IN VITRO METHOD PRACTICES (GIVIMP) 3 FOR THE DEVELOPMENT AND IMPLEMENTATION OF IN VITRO METHODS FOR 4 REGULATORY USE IN HUMAN SAFETY ASSESSMENT 5 6 FOREWORD 7 8 A guidance document on Good In Vitro Method Practices (GIVIMP) for the development and 9 implementation of in vitro methods for regulatory use in human safety assessment was 10 identified as a high priority requirement. The aim is to reduce the uncertainties in cell and 11 tissue-based in vitro method derived predictions by applying all necessary good scientific, 12 technical and quality practices from in vitro method development to in vitro method 13 implementation for regulatory use. 14 The draft guidance is coordinated by the European validation body EURL ECVAM and has 15 been accepted on the work plan of the OECD test guideline programme since April 2015 as a 16 joint activity between the Working Group on Good Laboratory Practice (GLP) and the 17 Working Group of the National Coordinators of the Test Guidelines Programme (WNT). 18 The draft document prepared by the principal co-authors has been sent in September 2016 to 19 all 37 members of the European Union Network of Laboratories for the Validation of 20 Alternative Methods (EU-NETVAL1) and has been subsequently discussed at the EU- 21 NETVAL meeting on the 10th of October 2016. 22 By November/December 2016 the comments of the OECD Working Group on GLP and 23 nominated experts of the OECD WNT will be forwarded to EURL ECVAM who will 24 incorporate these and prepare an updated version. -
Pax Large Cap Fund USD 7/31/2021 Port
Pax Large Cap Fund USD 7/31/2021 Port. Ending Market Value Portfolio Weight Microsoft Corporation 89,240,649.84 6.2 Apple Inc. 56,474,074.80 3.9 Alphabet Inc. Class A 45,168,406.39 3.1 Applied Materials, Inc. 40,802,748.42 2.8 United Parcel Service, Inc. Class B 40,145,031.68 2.8 Amazon.com, Inc. 40,024,252.52 2.8 Procter & Gamble Company 38,175,527.61 2.6 Alphabet Inc. Class C 37,288,542.96 2.6 T-Mobile US, Inc. 36,913,478.16 2.5 CVS Health Corporation 35,823,305.60 2.5 Bristol-Myers Squibb Company 35,683,263.33 2.5 Trane Technologies plc 34,492,144.83 2.4 Voya Financial, Inc. 34,364,677.20 2.4 Fiserv, Inc. 33,109,434.63 2.3 Medtronic Plc 32,631,060.24 2.2 Lowe's Companies, Inc. 32,345,328.78 2.2 JPMorgan Chase & Co. 31,275,786.80 2.2 salesforce.com, inc. 31,164,938.74 2.1 Aptiv PLC 30,049,685.00 2.1 Target Corporation 29,624,476.10 2.0 Becton, Dickinson and Company 29,334,525.00 2.0 Citizens Financial Group, Inc. 28,825,635.20 2.0 Merck & Co., Inc. 28,216,517.16 1.9 BlackRock, Inc. 28,142,268.01 1.9 Vertex Pharmaceuticals Incorporated 26,265,874.00 1.8 Lincoln National Corporation 25,842,318.84 1.8 Sysco Corporation 25,428,711.00 1.8 Equinix, Inc. -
PD2M Newsletter
PD2M Newsletter March 2020 Note from the Editor Our first issue of the PD2M Newsletter 2020 highlights two interesting topics: - Pharma 4.0: The term “Industry 4.0” was first used in Germany to incentivize modernization of manufacturing. The International Society for Pharmaceutical Engineering (ISPE) adapted it 2017 and the concept of “Pharma 4.0” was born. The Carla Luciani vision of highly efficient, vastly automated, self-driven manufacturing processes is extremely appealing to Pharmaceutical Discovery, practitioners. But separating hype from reality is important. Get Development and Manufacturing a feel of what is going on from Nima Yazdanpanah Forum, Newsletter Chair (Procegence), Shujauddin Changi (Vertex), Moiz Diwan (Abbvie), and Christopher Burcham (Eli Lilly) who reported RNA-Tx, Lilly Research Pharma 4.0 Highlights from the last AIChE Annual Meeting. Laboratories, Eli Lilly & Co. - Connect @ AIChE: Meet candidates in a poster session & reception at the 2020 AIChE Annual Meeting in San Francisco. If you are a graduate student/postdoc who are available for In this issue: employment by summer 2021 or you work in industry and want to meet new talent and grow connections, this is a great event Note from the Page 1 to do so. Learn everything you need to know here. Editor There is still more to come on PD2M programming and activities. Don’t Pharma 4.0 Page 2 miss future issues of the PD2M Newsletter. Highlights Connect @ AIChE Page 6 It is all about connectivity… 1 | Page Page | 1 Page | 1 PD2M Newsletter Pharma 4.0 Highlights from AIChE Annual Meeting 2019 The Pharma 4.0 paradigm, analogous to the The Pharma 4.0 was topic of two plenary sessions Industry 4.0, intends to utilize enabling technologies in the AIChE Annual meeting 2019 in Orlando, FL, in the pharmaceutical and biopharmaceutical held by PD2M and Next-Gen Manufacturing industries.