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Michael A. Grosso, MD, FACS Executive Director, CV Clinical Development Daiichi Sankyo, Inc.
Globalization is the need of trials – Conducting Clinical Trials around the globe for successful and long lasting effects
2 | CONFIDENTIAL 2 | CONFIDENTIAL
Global Drug Development 2016
Global Pharma Market value $300 Billion /year ~7,000 drugs currently in clinical development globally Only 1 in 10,000 compounds will actually be brought to market Only 2 of 10 marketed return revenues equal or exceed R&D costs 2015 Pharma invested $58.8 billion in R&D; 10% increase from 2014 10 year Patent to recoup R&D cost before generic competition 600% increase in drug development cost from 1970 to 2010 50% increase in Global Clinical trial market from 2011 to 2015
Sources: Aiello, Healthcare BusinessToday; Office of Health Economics CMRI Data Report; Krall, IOM Transforming Clinical Research
3 | CONFIDENTIAL 3 | CONFIDENTIAL
Global Drug Development 2016
~7,000 drugs currently in clinical development globally ~11,000 ongoing clinical trials with at least one US site Seeking to enroll nearly 3 million subjects
Sources: Aiello, Healthcare BusinessToday; Office of Health Economics CMRI Data Report; Krall, IOM Transforming Clinical Research
4 | CONFIDENTIAL 4 | CONFIDENTIAL
Global Drug Development 2016
Leading Trends/Challenges:
Source: BioPharmaDive/Catalent; *1/3 revenue $10+ Billion USD ** 1/5 market $163 billion 2014
* **
5 | CONFIDENTIAL 5 | CONFIDENTIAL
Global Drug Development 2016
Leading Trends/Challenges: Aging Population- longer, not healthier Rising #Age related and Chronic Diseases- $$
Cancer, CV, Neurolgic/Dementia Spiraling Development Costs Demands for Biologics-Complex analytical/manufacturing Increasing role of CRO/CDMOs Increasing Political/Legislative focus- access/cost of medication Interaction with Regulatory/Health Agencies Payers demanding “value proposition” Increasing Role of Generics/Biosimilars Enhanced Focus on novel Drug Delivery Mechanisms Enhanced Growth (and risk) Opportunities in Manufacturing Process Threat from Counterfeit Drugs- $75 Billion/year
Source: BioPharmaDive/Catalent
6 | CONFIDENTIAL 6 | CONFIDENTIAL
Global Drug Development 2016
Clinical Trial Trends/Challenges: RECRUITMENT
Incremental improvements: complex, long, large studies: mega-trials CV
Orphan drug development RETENTION
15-40% dropout REGULATORY SETBACKS / Poor
Communication w/ Health Agencies
FAILURES 50% of NDA/BLA failures due to
efficacy 30% of NDA/BLA failures due to safety
Source: BioPharmaDive/Catalent
7 | CONFIDENTIAL 7 | CONFIDENTIAL
Global Drug Development 2016
Clinical Trial Trends/Challenges: DEVELOPMENTAL COSTS :
Bench to Bedside: 12 + years, $2.6 billion USD (2013) $300+ million USD post-approval costs
PAYORS: “Real world” data beyond clinical trials; “p “value no longer sufficient Comparative effectiveness beyond SOC (often evolving rapidly) “Value” propositions
REGULATORS Greater post-marketing surveillance
INCREASING NEED/RELIANCE on CRO/CDMO Specialized technologies/technical support Biologics / Analytics Controlled Release/Combination formulations; enhance LCM/patent life
Source: BioPharmaDive/Catalent; Tufts Center Study Drug Development 2014
8 | CONFIDENTIAL 8 | CONFIDENTIAL
Global Drug Development 2016
Clinical Trial Trends/Challenges: OUTSOURCING MANUFACTURING steadily rising
Lower cost labor / land ? Offset by increased regulatory risk
STRATEGIC PARTNERSHIPS Risk and Profit sharing models for Drug development and Manufacturing
PDUFA / GDUFA Impact 21st Century Cures Act remains stalled
Source: BioPharmaDive/Catalent; Tufts Center Study Drug Development 2014
9 | CONFIDENTIAL 9 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
REGULATORY Regulators often require minimum numbers of patients from a specific
region or with specific ethnic factors to support a regulatory approval Inclusion of multiple ethnic populations in accordance with guidelines (ICE E5
Guidance on Ethnic Factors in the Acceptability of Foreign Clinical Data)
SCIENTIFIC Ethnic and population differences may lead to differential efficacy and safety
outcomes Growing understanding of human genome diversity enhanced by global
clinical trials
10 | CONFIDENTIAL 10 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
Forces Driving Clinical Trials outside US Availability of large numbers of patients Drug naïve subjects Trial naïve subjects Patients willing, eager to participate (access) CROs available and focused on global trials Faster recruitment rates
High urban density Shorter start up times: Reduced logistical barriers (contracts, regulatory) Shorter overall trial timelines Widespread adoption of harmonized guidelines ICH-GCP Intellectual Property protection Cost
11 | CONFIDENTIAL 11 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
Relative Cost of Clinical Trials outside US
Source: Kaitin, Tufts Center for Study of Drug Development 2008
12 | CONFIDENTIAL 12 | CONFIDENTIAL
Breakdown of Costs for a Large, Global Clinical Trial
Global Clinical Trials in 2016
Expense Cost ( %)*
Site Payments 50%
Site Monitoring 30%
Data Management and Statistics 8%
Project and Clinical Leadership 8%
Interactive Voice Response (IVRS); Drug distribution 3.5%
Publications 0.5%
Source: *Califf 2009;
13 | CONFIDENTIAL 13 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
Relative Cost of Clinical Trials outside US
Source: Tufts
India 0.36
Poland 0.39
Russia 0.41
China 0.50
Brazil 0.50
Germany 0.50
Argentina 0.65
Australia 0.67
USA 1.0
14 | CONFIDENTIAL 14 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
BRIC Brazil Russia India China Brazil: ~4000 active clinical sites 30% Oncology; 10% CV ANVISA overhaul/ ?economy
Russia ~7,000 sites, #10 globally 800 active trials, 60% Phase III
India 67% population rural based Healthcare GDP low # of active sites declining, <2,000 Cautious approach
China On track to be #2 global pharma market ~6,000 sites, ~48% oncology, 13th globally Strong focus on domestic driven development
Source: Goatman Applied Clinical Trials
15 | CONFIDENTIAL 15 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
Emerging countries will account for 29% of global pharma revenue by 2018 In 2012, Brazilian and Chinese pharma markets grew
by 16% and 21%, compared average market growth of - 2% for the five major EU and - 1 % for the U.S.
Number of US Investigators has declined 3.5% annually since 2001
Number of Investigators outside of US has increased 13.5% annually since 2001
Rare and chronic diseases require new patient pools
Delays and timeline extensions result in loss of millions of dollars AND Delay regulatory clearance, product
launch/sales
Source: Lionbridge LIFE SCIENCES; Bairu 2014
16 | CONFIDENTIAL 16 | CONFIDENTIAL
WHY are Global Clinical Trials Necessary in 2016
RECRUITMENT/RETENTION Increased competition Incremental improvements: complex, 2x long, large studies: mega-trials- CV Patient recruitment delay accounts for average 4.6 months lost per trial Lost revenue ~ $8 million UDS each day drug is delayed from market 80% of all trials delayed at least one month due to R/R issues Not an issue solely for industry- also affects NIH, academic organizations,
research foundations
Source: Lionbridge LIFE SCIENCES; Bairu et al 2014; Metadata Solutions 2013
17 | CONFIDENTIAL 17 | CONFIDENTIAL
Global Clinical Trials in 2016 Challenges Increased logistics Varied rules/regulations: contracts, insurance, legal documentation Cultural barriers / Translation (CRFs, IBs, ICs, Protocols) Religion/Contraception
Investigational drug provision at trial end Concomitant med provisions Acceptability of placebo controls
Source: Lionbridge LIFE SCIENCES; Bairu et al 2014; Metadata Solutions 2013
18 | CONFIDENTIAL 18 | CONFIDENTIAL
Global Clinical Trials in 2016 Recruitment/Retention barriers Subject-related
Inconvenient scheduling clinic visits / long clinic waiting times Uncertainty of treatment Unrealistic expectations/“mis”-Informed Consent Increasingly mobile work force
Investigator-related Lack of time/under-estimation of time needed for R/R Improper feasibility design/response
Protocol-related Study impact on local clinical practice Overly complex design
Others Lack of engagement of KOLS Negative media Unrealistic timelines Source: Sullivan, Applied Clinical Trials
19 | CONFIDENTIAL 19 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
20 | CONFIDENTIAL 20 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
21 | CONFIDENTIAL 21 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
23 | CONFIDENTIAL 23 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
24 | CONFIDENTIAL 24 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
25 | CONFIDENTIAL 25 | CONFIDENTIAL
Global Clinical Trials in 2016
Source: 2015 CISCRP Perceptions & Insights Study – All Respondents (n=12,009)
26 | CONFIDENTIAL 26 | CONFIDENTIAL
Global Clinical Trials in 2016 Challenges Increased logistics Varied rules/regulations: contracts, insurance, legal documentation Cultural barriers / Translation (CRFs, IBs, ICs, Protocols) Religion/Contraception
Investigational drug provision at trial end Concomitant med provisions Acceptability of placebo controls
Robust, critical FEASIBILTY Assessment Public education on value of Clinical Trial Participation Reliance on Local Expertise Full Service CRO / Risk-Cost sharing / Strategic Partnerships
Source: Lionbridge LIFE SCIENCES; Bairu et al 2014; Metadata Solutions 2013
27 | CONFIDENTIAL 27 | CONFIDENTIAL
Global Clinical Trials in 2016
Future Trends Impact of Brexit? EMA/CHMP
Electronic Medical Record EMR Potential for large scale registry/observational data
FDA Mini-Sentinel pilot project post-marketing surveillance Currently over 250 different providers Top five garner 50% market but lack consistent ability to share data effectively
across platforms Data Privacy HIPAA 1997 ?Update/Improvement
Mobile and Wearable Technology Insulin/glucose levels, Cardiac activity, Respiratory rate, CHF Rx Compliance/ RF chip