Biotech Tuft Outlook 2010

Published on June 2016 | Categories: Documents | Downloads: 26 | Comments: 0 | Views: 262
of 16
Download PDF   Embed   Report

Comments

Content

Tufts Center for the Study of Drug Development

OUTLOOK

2010
TUFTS UNIVERSITY

R&D EFFICIENCY REGULATORY ENVIRONMENT BIOTECHNOLOGY TRENDS PRESCRIPTION DRUG POLICY DRUG DEVELOPMENT MANAGEMENT TRENDS

C O N TA C T T H E T U F T S C E N T E R F O R T H E S T U D Y O F D R U G D E V E L O P M E N T

The following Tufts CSDD experts are available to comment or discuss a wide variety of topics relating to drug development.

CONTACT
Kenneth I Kaitin, Ph.D. Director, Professor of Medicine, Professor of Pharmacology & Experimental Therapeutics Tel Email 617-636-2181 [email protected]

EXPERTISE
Economic and regulatory environment R&D and corporate strategy Drug safety trends Risk management Stratified medicines development Impact of regulatory policy Fast-track program Pediatric initiative Counter-bioterrorism initiatives Global R&D and innovation Cost of drug development R&D efficiency Post-approval R&D Therapeutic class development trends

Christopher-Paul Milne, DVM, MPH, JD Associate Director Tel Email 617-636-2188 [email protected]

Joseph A. DiMasi, Ph.D. Director of Economic Analysis Tel Email 617-636-2116 [email protected]

Joshua P. Cohen, Ph.D. Senior Research Fellow Tel Email 617-636-3412 [email protected]

Prescription drug policy Formulary trends Follow-on drug development trends Prescription-to-over-the-counter switching

Ken Getz, MBA Senior Research Fellow Tel Email 617-636-3487 [email protected]

Drug development management trends Contract research organizations International clinical trials E-technologies in drug development

Janice M. Reichert, Ph.D. Senior Research Fellow Tel Email 617-636-2182 [email protected]

Biotechnology trends Protein therapeutics Vaccine development trends

Richard I. Shader, M.D. Senior Research Fellow & Medical Consultant Professor Emeritus, Pharmacology & Experimental Therapeutics Tel Email 617-636-3856 [email protected]

Experimental design Clinical pharmacology and therapeutics Ethics

ABOUT

TUFTS CSDD AND THIS

REPORT

is to develop strategic information to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization. Kenneth I Kaitin, Ph.D., who has served as director of Tufts CSDD since 1998, leads a team of 10 research professionals and four support staff who serve to:
G Monitor and report on the development,

S

ince it was established in 1976, the Development at Tufts University has

The Tufts CSDD Outlook, published each January, showcases the Tufts Center’s view on near-term pharmaceutical and biopharmaceutical drug development trends. Data contained in Outlook 2010 are based on proprietary research conducted by Tufts CSDD. Analyses are based on the ongoing work of the Tufts Center’s senior staff, who confer regularly with a broad range of pharmaceutical and biopharmaceutical leaders, as well as with regulators, service providers, investors, and others involved in the research-based industry. Outlook reports constitute one element of a full range of information and related services on and for the research-based drug industry and other stakeholders in pharmaceutical innovation. Other Tufts CSDD offerings include professional educational seminars and workshops, symposia, and public forums on related topics. In addition, the Tufts Center publishes the Tufts CSDD Impact Report, a bi-monthly newsletter providing analysis and insight into critical drug development issues. Research findings developed by Tufts CSDD are regularly published in peer-reviewed, trade, and business publications.

Tufts Center for the Study of Drug served as an independent, academic,

nonprofit research group. Its mission

regulation, and utilization of new drugs and biopharmaceuticals.
G Explore the economic, legal, scientific, and

public policy issues affecting pharmaceutical and biopharmaceutical innovation worldwide.
G Provide information on the development and

review of new therapeutic agents.
G Sponsor public forums and conferences that

bring together the perspectives of government, industry, academia, and public health advocates.
G Raise the level of national and international

For more information, call 617-636-2170 or click on http://csdd.tufts.edu.

debate on issues related to new drug and biotechnology product development and regulation.

© 2010 Tufts University. All rights reserved. No part of this Outlook 2010 report may be reproduced, transmitted, or distributed by any means, mechanical or electronic, in whole or in part, without written permission of the Tufts Center for the Study of Drug Development.

1

G L O S S A RY
Approval success rates — The percentage of NCEs in clinical development that eventually obtain marketing approval from the United States Food and Drug Administration (FDA). Biomarker — A characteristic that is objectively measured and evaluated as an indicator of normal
biologic or pathogenic processes or pharmacological responses to a therapeutic intervention.

Biosimilar — A follow-on, approved biopharmaceutical that is biologically similar to an existing medicine. CRO — Contract Research Organization. An organization that manages various steps in the drug development process, including conduct of preclinical studies, clinical study design and execution, data management, analysis, medical writing, and regulatory submission. EMEA — European Agency for the Evaluation of Medical Products. A decentralized body of the European Union, based in London, charged with protecting and promoting public and animal health, through the evaluation and supervision of medicines for human and veterinary use. A regulatory agency analogous to the FDA. NCE — New chemical entity. A new therapeutic compound that has never been used or tested in
human subjects.

NDA — New drug application. An application to FDA for a license to market a new drug. Monoclonal antibody (mAb) types — Murine mAbs are derived from mouse genes; human mAbs are
derived from human genes; chimeric and humanized mAbs are each derived from varying amounts of mouse and human genes, with the humanized products containing more human protein sequence than the chimeric versions.

Off-label prescribing — The practice of prescribing medicines for an unapproved indication. While doctors in the U.S. and elsewhere may legally prescribe a drug off-label, it is illegal for drug makers to promote off-label uses for their products. Orphan drug — Drug developed for a rare disease or condition, which, in the U.S., affects fewer than
200,000 people, or, in the European Union, affects 5 per 10,000 people or fewer. Because sales of orphan drugs are likely to be small compared to their development costs, sponsors are awarded exclusive rights to market these medicines for a period of time as an incentive to develop them, in addition to access to tax credits, R&D grants, fee waivers, and FDA technical and scientific advice.

PDUFA — The Prescription Drug User Fee Act of 1992. Legislation passed by the U.S. Congress authorizing
the FDA to collect user fees for regulatory review of new drug applications. The FDA agreed to use the revenue generated from user fees to hire more reviewers to speed up the drug review process without compromising review quality. PDUFA was reauthorized in 1997, 2002, and 2007.

Phase transition probability — The likelihood that an investigational new compound that begins a
particular development phase will transition to the next development phase.

Protocol — A plan detailing the methodology of a clinical trial.

2

OUTLOOK2010
objectives, greater emphasis on team participation in individual performance reviews, and the forging of more collaborative relationships with outside service providers.

prescription products, ranging from mass market blockbuster drugs to medicines targeted at highly defined populations. While the full impact of these actions is not yet known, initial indications are encouraging. Tufts CSDD research suggests that drug sponsors are becoming more aggressive about terminating unpromising candidates, enabling companies to redirect resources to other projects. Helping to drive this change is the growing use of forward-looking development metrics that link operational goals with company business

T

he research-based drug industry is Much work, however, remains to be done, as only three in 10 new drugs, on average, generate sufficient revenues to sustain R&D. The challenge for drug developers is not only to improve R&D performance in the short term, but also to transform the way they conduct research and development over the medium and longer term to be more efficient and productive. Greater use of biomarkers and information technology, improved protocol designs, and better recruitment and retention of volunteers are helping today. Going forward, sponsors will likely find that much of their success will flow from their ability to collaborate with other drug companies at specific points on the development spectrum, how well they engage and partner with outside service providers, and the way they work with academia and other stakeholders in the drug development process.

working overtime to transform itself into a leaner, faster-paced version

of its traditional self, as patents

continue to expire for dozens of

DEVELOPMENT AND APPROVAL TIMES HAVE SHORTENED, BUT HAVE THEY DROPPED ENOUGH?
Clinical development and FDA approval times for new drugs
Clinical Phase
10 9 8 7

Approval Phase

PDUFA Enacted

Years

6 5 4 3 2 1 0
1984-86 1987-89 1990-92 1993-95 1996-98 1999-01 2002-04 2005-07

Drug developers and the FDA have worked hard to speed up drug development since PDUFA was enacted in the early 1990s: total average clinical time dropped 10% from 1992 through 2007, even as trials became more complex, while average approval time declined nearly 60%. However, it still costs more than $1 billion and takes more than seven years, on average, to conduct clinical trials and win approval to market a new drug. Although developers are terminating more unpromising drugs earlier and teaming with outside service providers to streamline development, new product approvals are not keeping pace with patent expirations.

Source: Tufts Center for the Study of Drug Development

3

R&D EFFICIENCY
Although drug developers continue to explore new process strategies to improve the efficiency of drug development, the output of new drugs continues to lag, with the likelihood of obtaining regulatory approval for investigational drugs remaining low.
G Companies will refine their benchmarking metrics

to better balance objectives across program areas to improve performance from the study level, up through the company’s full R&D portfolio.
G More firms will focus on improving clinical

protocol design to mitigate a trend toward increased protocol complexity—to reduce trial costs and speed development cycles.
G As firms seek to learn more from Phase I trials,

they will increase their use of biomarkers and diagnostic tests, rely more on patient volunteers, and conduct more integrated studies to examine multiple clinical issues.
G Drug licensing activities increasingly will focus

on building long-lasting relationships between partners, in part, by shifting from traditional milestone and royalty fee arrangements to equity-based agreements that can also facilitate an acquisition strategy.
G Although drug companies will continue to use

external service providers, such as CROs, on a transactional basis to meet short-term objectives, they will experiment with value-added outsourcing involving a high degree of integra-

NEW DRUG DEVELOPMENT REMAINS A VERY RISKY VENTURE
Transition probabilities between phases of drug development
100%

tion between both parties, which will include cost and risk sharing with external partners and, in some cases, equity investments.

1 1993-98
75%

1999-04 1

50%

25%

0%
Phase I to II Phase II to III Phase III to NDA Submission NDA Submission Phase I to to NDA NDA Approval Approval

Despite efforts to improve the predictability and likelihood of overall clinical approval success, only one-in-six self-originated compounds developed by the 50 largest global pharmaceutical firms that enter clinical testing eventually obtain marketing approval. However, declining clinical transition probabilities between Phase I and Phase II, and between Phase II and Phase III, suggest that drug sponsors are becoming more aggressive about terminating unpromising candidates, enabling them to re-direct increasingly scarce R&D resources to more promising drug development programs.

Source: Tufts Center for the Study of Drug Development

4

R E G U L AT O R Y E N V I R O N M E N T
The FDA will struggle to overcome approval delays stemming from new policies and procedures; globalization will see more cooperation among sovereign regulatory agencies.
G FDA’s drug approval process will face a number

of challenges: integrating 700 recent hires, implementing the new 21st Century Review program, going paperless, handling more pharmacogenomic data, and increasing reliance on REMS and advisory committee meetings, which help the agency address safety concerns, but can prolong review time.
G Globalization will demand increasing coopera-

tion among the major regulatory agencies, such as the U.S.-China initiative on product safety, a U.S.-Japan-EU project on biomarker validation, and U.S. partnering with India to enhance its regulatory capacity for emerging technologies.
G After the U.S. Congress concludes the health

care reform debate, a more “activist” FDA will emerge on a number of fronts, including a regulatory pathway for follow-on biologics approvals, OTC product and drug safety, foreign facility inspections, preventable deaths from chronic diseases, and vaccine manufacturing capacity.
G Increased scrutiny from the FDA, state attorneys

general, and the plaintiffs’ bar is expected to make the cost of doing business in the biopharma world more expensive, following Pfizer’s

RISK MANAGEMENT IN THE U.S. WILL CONTINUE TO BE A GROWING BUSINESS
Comparative numbers of drug development risk plans

$2.3 billion settlement for illegal marketing and the Supreme Court’s Wyeth v. Levine decision that FDA-approved labeling does not pre-empt state laws or shield companies from legal damages as part of liability claims.

# of RMPs per year, 2002-06

# of existing RiskMAPs in early 2007

# of RiskMAPs submitted in FY2007 REMS approved from end of March to mid-Sept. 2009 0 10 20 30 40 50 60 70

RMP = Risk Management Plan; RiskMAP = Risk Minimization Action Plan; REMS = Risk Evaluation and Mitigation Strategy Source: Tufts Center for the Study of Drug Development, FDA

FDA risk management requirements are increasing in scope, number, and degree of authority. Throughout most of the early 2000s, risk management was based on FDA position papers and reports. Following the withdrawal of Vioxx from the market in 2004 and increasing FDA oversight, RiskMAP submissions surged by 75%, as have the number of REMS subsequently approved in 80 connection with expanded FDA authority granted by the FDA Amendments Act of 2007.

5

B I OT E C H NO L O G Y T R E N D S
As protein products approved in the 1980s and early 1990s lose patent protection, marketing approvals for biosimilars will increase in the European Union, and these products may become viable in the U.S.
G Pending Congressional legislation that defines

a regulatory pathway for biosimilars, which are called ‘follow-on protein products’ in the U.S., will pave the way in the near term to allowing the FDA to approve biosimilars.
G Given the growth of monoclonal antibody

(mAb) approvals—from less than 15% of all approvals during the 1980s and early 1990s to 30%-35% of approvals during 1995-09—the European Agency for the Evaluation of Medical Products (EMEA) may issue guidelines on the development of biosimilar antibodies in the near future.
G Clinical development time for novel protein

products, which has steadily lengthened since the 1980s when products such as somatropin were first approved, and now averages 7 years, is unlikely to decrease due to disease complexity, growth of study protocols that lengthen studies, and difficulty recruiting and retaining volunteers.
G Expanded development of mAbs worldwide

supports expected continued global sales

WHILE CLINICAL TIMES FOR BIOTECH PRODUCTS LENGTHEN, MORE ARE GETTING TO MARKET
Phase lengths for FDA-approved novel recombinant proteins and mAb therapeutics
Clinical Phase
100

growth of 14% per year through 2012.

Approval Phase

80

60

40

20

The biotechnology industry initially focused on development of recombinant protein products with well-known functions, e.g., somatropin, epoietin, filgrastim, insulin, and interferon. On average, the clinical development period was 2.5 years for products like these that were approved in the 1980s. In contrast, novel protein products approved recently have taken over 7 years on average to complete the clinical studies required for FDA review.

0

1982-89 (n=8)

1990-94 (n=9)

1995-99 (n=20)

2000-04 (n=31) 2005-09* (n=20)

* FDA approvals through October 1, 2009 Source: Tufts Center for the Study of Drug Development

6

PRESCRIPTION DRUG POLICY
Implementation of a federal comparative effectiveness research program in 2010 will change the health technology assessment landscape in the U.S.
G Systematic clinical and cost-effectiveness eval-

uation of newly approved biopharmaceuticals will become common practice among virtually all payers.
G Private payers will use federal comparative

effectiveness research findings to determine coverage of outpatient prescription drugs, particularly for the Medicaid and Medicare populations.
G An increasing number of private payers will

resort to value-based insurance design, i.e., adjustment of out-of-pocket costs based on an assessment of the clinical and cost-benefit value to a specific patient population.
G Off-label prescribing of biopharmaceuticals will

be subject to increased economic scrutiny, such as comparative effectiveness assessments, drug utilization reviews, and prior authorization.

SPECIALTY BIOLOGICS PLAY A GROWING ROLE IN U.S. HEALTH CARE, BUT INSURANCE COVERAGE IS UNEVEN
Current Medicare payer coverage of monoclonal antibodies (mAbs)
D Drugs covered
100%

D Drugs with reimbursement conditions
While the vast majority of mAbs—many being specialty biologics targeting various cancers—are covered by Medicare Part B, with a small share subject to conditions of reimbursement, a larger share of Part D mAbs is excluded from coverage, and many of the covered drugs have conditions of reimbursement. Furthermore, Tufts CSDD studies show that approximately one-quarter of payers regularly deny reimbursement for off-label uses of Part B and Part D mAbs, and that conditions of reimbursement are imposed on 92% of those off-label uses.

80%

60%

40%

20%
0%

Medicare Part B

Medicare Part D

Off-label use

Source: Tufts Center for the Study of Drug Development

7

DRUG DEV ELOPMENT M A NAG E M E NT T R E N D S
Facing mounting pressure to achieve higher levels of performance and efficiency, sponsors are looking to improve protocol design and establish more integrated relationships with CROs and investigative sites.
G Sponsors increasingly are seeking to balance

their protocols’ scientific and operating objectives in response to increasing design complexity— more so for certain therapeutic areas than others—and growth in the number of amendments per protocol.
G Sponsors, reporting a high proportion of unused

data in regulatory submissions, will also seek higher levels of efficiency and reduction in protocol design burden placed on study staff and volunteers.
G To better utilize capacity and proactively manage

portfolio demands, sponsors will develop better resource planning and forecasting methodologies that rely on more integrated relationship structures with contract research organizations (CROs).
G A tougher global operating environment that is

forcing marginal research sites to exit clinical development will ultimately create a less fragmented global development landscape; higher performing research investigators will be avail-

DRUG DEVELOPMENT WILL INCREASINGLY INVOLVE PARTNERSHIPS BETWEEN SPONSORS AND THIRD PARTIES
Global demand for clinical services outsourcing
Total development spending (left axis) Total spending on contract clinical services (right axis)
60 50 12 10

able to partner with sponsors.

40 30 20 10 0

8 6 4 2 0

While global spending on new drug development has been growing at an annual rate of 9.1% during this past decade, spending on contract clinical services has been growing nearly 50% faster—at an annual rate of 13.4%. Even as the number of companies with active clinical projects worldwide increased by 80% between 2000 and 2008, sponsors have kept their R&D headcount level by working with CROs. The trend to work even closer—to improve R&D efficiency—will continue as both parties develop alliances in place of traditional transactional relationships.

Billions of U.S. Dollars

Billions of U.S. Dollars

2001

2003

2005

2007

2009P

Note: Does not include pass-through clinical services, e.g., central lab fees, investigator grants Source: Tufts Center for the Study of Drug Development

8

AGENDA
Drug Licensing Trends
Progress in Translational Medicine Orphan Products Update Personalized/ Stratified Medicines Development and Investment Trends Innovation Efficiency in Developing Countries Antibody Treatments for Immunological Diseases Novel AntibodyBased Therapeutics Peptide Therapeutics Development Pharmacogenomics
therapeutic class.

TUFTS CSDD RESEARCH PROJECTS DUE FOR COMPLETION

2010

Examination of trends in the extent to which firms license-in investigational drugs, by firm size and

As part of its ongoing project on a number of inter-related innovation initiatives, including the FDA’s Critical Path and EMEA’s Innovative Medicines Initiative, Tufts CSDD will collaborate with the University of Edinburgh on a book in 2010. Update on the R&D and market metrics for orphan products.

Assessment of personalized medicine R&D strategies, extent of focus in company pipelines, and current development challenges.

Examination of indigenous, regional, and international programs that foster sustainable biopharmaceutical innovation, allowing countries to address unmet medical needs.

Evaluation of pipeline and approved antibody therapeutics studied as treatments for immunological diseases, such as rheumatoid arthritis.

Analysis of the potential market for next-generation therapeutics that are alternative scaffolds or derived from antibodies. Update of key metrics, such as probabilities of approval success and development times, for synthetic peptide therapeutics. Case study analysis of clinical and economic applications of pharmacogenomics.

Oncology Therapeutics Comparison of U.S. and Australian access to recently approved oncology drugs. Market Access Evaluating Protocol Amendments Program Design Complexity Global Investigative Site Landscape
Assessment of the incidence of protocol amendments, why they occur and how to prevent them.

Analysis of factors driving drug development program-level complexity and their impact on program costs, time lines, and quality. Assessment of infrastructure and capacity of global investigative sites participating in FDA- and EMEAregulated clinical trials and trends impacting this landscape.

9

TUFTS CSDD RESEARCH MILESTONES
D R U G P O L I C Y A N D S T R AT E G Y A N A LY S E S T O I N F O R M R & D A N D S T R AT E G I C P L A N N I N G D E C I S I O N S
Identifies “drug lag”: delayed drug availability in the U.S. compared with the UK. Conducts first comprehensive study of the cost to develop a new drug: $54 million. Demonstrates dramatic decline in effective patent life for new therapeutic compounds. Completes first analysis of availability of drugs for limited populations, paving the way for the Orphan Drug Act of 1983.

1976 1979 1981 1982 1984 1987 1991 1993 1995 1996-97 1997 1999 2000 2001 2003 2004 2005 2006 2007 2007 2008 2009

Develops first comparison of the rate of drug safety withdrawals in the U.S. and abroad. Publishes first comprehensive analysis of the FDA’s practice of requiring post-approval research as a condition of approval. Updates its seminal drug cost study: it now costs $231 million to develop a new drug. Develops first international comparison of biotechnology product discovery, development, and marketing rates in the U.S., Europe, and Japan. Publishes first comprehensive analysis of biotechnology success rates. Provides data and public testimony at Congressional hearings that led to passage of the FDA Modernization Act of 1997 (FDAMA). Completes comprehensive analysis of FDA/sponsor meetings, showing that meetings reduce the time of new drug development. Provides first comprehensive analysis and review of FDAMA’s pediatric research incentive program. Publishes first comparative analysis of new drug and biopharmaceutical approval times under the Centralized Procedure of the European Medicines Evaluation Agency (EMEA) and the FDA. Updates its ongoing analysis of average cost of pharmaceutical R&D. It now costs $802 million to develop a new drug and bring it to market. Provides first assessment of the impact of the FDA’s new fast track program on total development times. Completes first extensive analysis on the economics of follow-on drug development and incremental innovation. Provides quantitative evidence demonstrating the lack of correlation between drug safety withdrawals and speed of regulatory approval. Publishes first comprehensive estimate of the average cost of developing a new biotechnology product, and pegs it at $1.2 billion. Publishes extensive analyses on oncology drug R&D. Overall approval success rate is 8%. Provides comprehensive analysis of gender, ethnic, and racial disparities among clinical investigators. Publishes quantitative analysis demonstrating that U.S. drug plans, in covering 88% of drugs in six specific therapeutic areas, are non-compliant with Medicare regulations. Updates its ongoing analysis of new drug clinical success rates. Overall clinical success rates have fallen to 16%.

10

TUFTS CSDD EDUCATIONAL PROGRAMS
T U F T S C S D D E D U C AT I O N A L P R O G R A M S
FEBRUARY 8-12 Boston

Postgraduate Course in Clinical Pharmacology, Drug Development, and Regulation
For more than three decades, the Tufts CSDD Postgraduate Course has provided advanced instruction in clinical pharmacology, drug development, clinical trial strategies, biopharmaceutical development, drug safety, and the regulatory process. The 2010 course features lectures, breakout groups, and an interactive panel discussion. Over five days, expert faculty will examine clinical trial ethics, outcomes research, epidemiology, and information technology in clinical development. The program includes an interactive, mock presentation to regulators, providing participants with a unique opportunity to identify and analyze the impacts of drug design protocols on the regulatory process.

FEBRUARY 25 Boston

Tufts CSDD Executive Forum Roundtable — Improving ROI and Late Stage Clinical Success Rates
This program brings together senior pharmaceutical and biopharmaceutical industry R&D executives to discuss strategic R&D issues and new approaches that will guide the research-based industry to future success. Read more on Inside Back Cover.

MAY 13 Boston

Tufts CSDD Executive Forum Roundtable — Strategies for Managing Drug Development Risk: Maintaining Portfolio Diversity
See Inside Back Cover.

JULY 14-15 Boston

Leadership for Drug Development Teams: Improving Cross-Functional R&D Performance
Designed in collaboration with industry R&D leaders, the curriculum is based on challenges experienced by hundreds of development teams, program managers, and functional directors. Two-thirds of the course is devoted to hands-on casework, with the rest focused on interactive discussions with faculty. Attendance is limited to 35.

SEPTEMBER 16 Boston

Tufts CSDD Executive Forum Roundtable — Outsourcing Strategies Across the Value Chain
See Inside Back Cover.

NOVEMBER 4 Boston

Tufts CSDD Executive Forum Roundtable — Strategies for Optimizing the Drug Development Process: Translational Science, New Technologies, and Clinical Design Improvements
See Inside Back Cover.

LOOKING AHEAD... FEBRUARY 2011 Boston

38th Annual Postgraduate Course in Clinical Pharmacology, Drug Development, and Regulation
See description above.

For more information about these programs, call the Tufts Center for the Study of Drug Development at 617-636-2170, email us at [email protected], or click on the Courses & Forums link at http://csdd.tufts.edu.

11

KEEP CURRENT ON DRUG DEVELOPMENT TRENDS WITH THE

TUFTS CSDD I M PAC T R E P O RT

A bi-monthly, authoritative analysis of critical drug development issues, highlighting current research of the Tufts Center for the Study of Drug Development.

The Tufts CSDD Impact Report has become must reading for professionals worldwide looking to understand the current state of drug development and regulation. Presented in a concise, easy-to-read format, each issue delivers original research, analysis, and insight on a host of mission-critical topics relating to the nature and pace of drug development and regulation.

Readers consistently describe Tufts CSDD Impact Reports as “thoughtful and timely,” “excellent,” and “a real asset.”

2010 Editorial Calendar:
January/February — Orphan drug development update March April — Regulatory affairs department structures and functions June/July — Development of biosimilar therapeutics July/August — Innovation diffusion September/October — Personalized medicines in development November/December — Supplemental indication development and approval metrics

Volume 11 Number 5 • September/October 2009

Tufts Center for the Study of Drug Development
The growth rate of total principal investigators worldwide has slowed since 2001
Number of Individual Principal Investigators
18000 U.S.-Based 16000 14000 12000 10000 8000 6000 Non-U.S.-Based

In all, 26,145 individual PIs conducted FDAregulated clinical trials worldwide in 2007. While the number of PIs worldwide grew at an annual rate of 8.7% from 1990 to 2007, since 2001 growth has been slower, at 2.1% annually. The number of active PIs in the U.S. declined 3.5% annually since 2001, while active PIs outside the U.S increased 13.5% each year during that same period. Annual growth in non-U.S. based PIs is due to several factors, including greater economic advantages and fewer regulatory constraints abroad.
Volume 11, Number 6 • November/December 2009

Impact
Tufts Center for the Study of Drug Development

TUFTS UNIVERSITY

REPORT

ANALYSIS AND INSIGHT INTO CRITICAL DRUG DEVELOPMENT ISSUES

Volume 11 Number 3 • May/June 2009 4000
2000

Tufts Center for the Study of Drug Development

0

1990

1992

1994

1996

1998

2000

2002

2004

2006

Impact

TUFTS UNIVERSITY

Source: Tufts Center for the Study of Drug Development

Impact
of prescription drugs
Of the plans that reimburse off-label uses, no plan excludes specific therapeutic classes from off-label use reimbursement. For plans that reimburse off-label uses, over half impose restrictions, relating to step therapy, indication, prior authorization, and quantity limits. Close to a quarter of the plans that impose restrictions on off-label use reimbursement follow Medicare National Coverage Determination policies on off-label uses of anti-cancer drugs.

Marketing exclusivity for first-in-class drugs R E P O R T has shortened to 2.5 years
Follow-on approvals underscore competitive nature of new drug development
Volume 11 Number 1 • January/February 2009

TUFTS UNIVERSITY

The share of principal investigators based in the United States continues to decline

REPORT
100% 60% 40% 20% 0%

Global Distribution of Total FDA-Regulated Principal Investigators
North America Western Europe Rest of World

The proportion of PIs based in the U.S. has steadily declined, from 96% of the total global pool of FDAregulated investigators in 1990 to 54% in 2007. Latin America, Eastern Europe, and Asia have seen 75% FDA-regulated reimburse for off-label use rapid growth in of U.S. payersPIs, mostly for confirmatory, Payerstage clinical studies. later Reimbursement Policies for Off-Label Uses

ANALYSIS AND INSIGHT INTO CRITICAL DRUG DEVELOPMENT ISSUES

ANALYSIS AND INSIGHT INTO CRITICAL DRUG DEVELOPMENT ISSUES 80%

Therapeutic peptides in clinical study in 2000-07 nearly doubled 1990s rate
1997 1999 2001 2003 2005 2007

Growth in PI-involvement in early, first-in-man clinical studies has been slower outside North Exclude off-label reimbursement America.
Don’t 8.5% of active FDA-regulated PIs are based in exclude – no restrictions Central and Eastern Europe. Asia and Latin Don’t exclude – but have restrictions America each host 5.5% of all PIs.

Drug approvals for neglected diseases increase along with more R&D funding
HIV/AIDS and malaria drugs accounted for 81% of approvals in 2000-09
The annual rate of new product approvals for neglected diseases increased from an average of 1.8 in 1975-99 to 2.6 in 2000-09. Tufts CSDD found that 33 drugs targeting tropical diseases and tuberculosis had been approved worldwide in 1975-99, compared to 16 approvals reported in a landmark 2002 study. Between 1999 and 2008, annual funding for neglected diseases had risen 25-fold to $2.5 billion.

Tufts Marketing exclusivity periods for first-in-class drugs have fallen dramatically in Center recent decades – from a median of 10.2 years in the 1970s to 2.5 years in the 2000-03 period.
Average time between first and second follow-on drugs fell even more rapidly – from a median of 16.1 years in the 1960s to 1.1 years in 2000-03. Nearly one-third of all follow-on drugs have received a priority rating from the United States Food and Drug Administration (FDA).

for the Study of Drug Development
TUFTS UNIVERSITY

Impact

REPORT

ANALYSIS AND INSIGHT INTO CRITICAL DRUG DEVELOPMENT ISSUES
Since the early 1990s, 90% of follow-on drugs had initial pharmacologic testing and 87% were in clinical studies somewhere in the world prior to the first-in-class drug approval.

Approval success rates have remained steady – in the 21%-24% range

Source: Tufts Center for the Study of Drug Development

Patent filings for follow-on drugs often occur in advance of first-in-class patent filing.

Of 318 therapeutic peptides included in the analysis, 42% are currently in clinical Snapshot of the FDA-Regulated PI Landscape development, with the remainder either in regulatory review, approved in at least Male Female one country, or terminated.
Share of all board certified physicians Phase II 68% of products that entered clinical study during 2000-07 are in Phase I orthat are PIs Average age studies. Total number of clinical trials 16.9% 51 10.9% 47*

Gender and racial disparities among PIs limit patient access to clinical trials
Minority 8.6% 44**

The majority of PIs (85%) are white, older males, with moreSource: Tufts Center for the Study of are more infrastructure support, and Drug Development likely to be located in rural and suburban locations. A substantially smaller proportion of female and Officially Recognized Compendia Cited for minority board certified physicians participate in Use in Determining Off-Label Reimbursement FDA-regulated trials than do male and Caucasian physicians, respectively.
American Hospital Formulary Service

Current investigator landscape poses a growing challenge for sponsors

Nearly 90% of respondents say compendia play a role in off-label reimbursement decisions
60% of respondents say that, to be reimbursed, off-label uses must be referenced in one or more pharmaceutical compendia. About 35% report that compendia play a primary role, while 50% said that compendia play a secondary role. Only 9% say that compendia play no role. The American Hospital Formulary Service (AHFS) is the compendium cited most often by respondents, followed by the United States Pharmacopeia Dispensing Information compendium and the Thomson Micromedex DrugDex. Vaccines have displaced drugs as the primary products being developed for neglected diseases. Public-private partnerships for new product development accounted for 46% of all approvals to treat neglected diseases in 2000-09, up from 15% in 1975-99. Government currently contributes 69% of all R&D funding for neglected disease drug development.

I

The average annual number of therapeutic peptides entering clinical study in the conducted since beginning 2000-07 period nearly doubled, to 16.9 from 9.7 during the 1990s. involvement
Mean number of patients served per PI During 2000-07, new peptides entering clinical development were most frequently Mean number of full-time studied as treatments for metabolic (26%) indications, one of 15 therapeutic areas in and part-time study coordinators per PI which peptides were being developed. Share of PIs located in urban/inner

51 4,649 9, 5

17* 1,996 4, 2

36 5,178 3, 2 62%

n contrast to popular belief that development of follow-on drugs—sometimes called Number of subjects per “me-too” drugs—begins after the first new drug in a therapeutic category receives new drug application declined steadily over 10 years marketing approval, the fact is that development of nearly all follow-on drugs actually begins well before the first-in-class drug is approved. New drug development remains The proportion of principal investigators (PIs) based in the United States has steadily a competitive race, and the first candidate to receive marketing approval belongs to thefrom 96% of the total global pool of FDA-regulated investigators in 1990 to declined, sponsor that completes the development gauntlet first. 54% in 2007.

Significant gender and racial disparities limit patient access to clinical trials and suggest that United States Pharmacopoeia there is an untapped pool of PIs available Dispensing Information to conduct industry-sponsored clinical studies. Thomson Micromedex
DrugDex Other American Medical Association Drug Evaluations

city locations 57% 72% Average total clinical study and FDA approval time for new therapeutic peptides was * Significantly different from male PIs at p<.01 level 10.8 years.
** Significantly different from Caucasian PIs at p<.01 level

Efficacy issues and commercial considerations were most often cited asU.S. PIs only; male and female include all ethnicities; Note: reasons for minorities includes both genders discontinuing clinical studies of new therapeutic peptides.
Source: Tufts Center for the Study of Drug Development

Source: Tufts Center for the Study of Drug Development

A

O

Tufts CSDD Impact Report • page 2 ver the last three decades therapeutic peptides have emerged as a therapeutically and commercially important class of drugs, with growth driven in part by advances in synthetic, delivery, and formulation technologies. Forty-eight therapeutic peptides are now on the market worldwide, with four reaching global sales of more than $500 million each in 2007. The pharmaceutical industry has steadily increased its investment in the development of these products through internal development programs as well as by acquisition, in-licensing, and joint development programs. New therapeutic peptide product development is expected to continue at a strong pace.

Volume 11, Number 1 • January/February 2009

widely circulated study in 2002 reported that only 16 of the 1393 new chemical entities marketed between 1975 and 1999 targeted tropical diseases and tuberculosis. However, a new Tufts CSDD analysis, summarized here, has found that the more accurate count is 33. Still, the earlier report served as a call to action for governments, nonprofit foundations, private-public partnerships, and private industry to devote more resources to battle neglected diseases.

A new Tufts CSDD study, summarized here, suggests that distinctions about innovativeThe number of active PIs in the U.S. declined 3.5% annually since 2001, while active ness drawn between first-in-class and follow-on drugs may not be meaningful. Indeed, the U.S increased 13.5% each year during that same period. PIs outside since the early 1990s, nearly one in three follow-on drugs had entered clinical testing Gender and racial disparities among PIs suggest that there is an untapped pool of earlier than did the first-in-class drug. In addition, approximately one-half of what investigators who could potentially provide increased enrollment of women and turned out to be follow-on drugs had a U.S. or worldwide patent filed before the firstminority patients in clinical trials. in-class drug had filed any such patents. These findings highlight the fact that, in the highly competitive pharmaceutical market, drug companies are, in effect, more often The number of PIs per active IND has nearly doubled during the past decade, while engaged in development races than in after-the-fact imitation. the proportion of clinical trials in Phase I has increased substantially. Complaints of PI non-compliance and fraud as a proportion of active clinical trial activity have been increasing since 2003.

Health plans also rely on peer-reviewed literature to guide off-label use reimbursements
Importance of Other Sources in Determining Off-Label Reimbursement
Very Important 100% 80% Important Not Important Not Applicable

More than three-quarters of survey respondents ascribe a “very important” role to peer-reviewed literature as a factor in determining off-label use reimbursement decisions. More than half of plans attribute a “very important” role to clinical practice guidelines. Almost four-fifths of plans ascribe a role to cost-effectiveness in off-label use reimbursement decisions, with almost one-fifth saying costeffectiveness data play a “very important” role.

Between 2000 and 2009, a significant increase in R&D for neglected diseases has led to 26 drugs and vaccines receiving worldwide marketing approval, over 80% of which target malaria and HIV/AIDS. While increased approvals are necessary to improve access, policymakers need to ensure that safe, effective, and easy-to-administer products are adopted by health care systems and providers on a consistent basis, that they are affordable, and that they reach the people who need them.

T

To better understand clinical development and approval trends for these products, Tufts CSDD assessed data on 318 therapeutic products that entered clinical development sponsored by commercial firms worldwide. Key findings are presented in this Tufts CSDD Impact Report and will serve as a baseline against which future growth will be measured.

60% 40% 20% 0% Peer-reviewed literature Clinical practice guidelines Cost-effectiveness data

he global clinical investigator landscape is changing rapidly. Perhaps most dramatically, the share of PIs worldwide, who are based in the U.S. has dropped nearly in half since 1990. More favorable economics elsewhere, fewer regulatory constraints, and well-positioned global contract research partners are prime factors behind this shift. In addition, active INDs now involve more PIs, with each PI enrolling smaller numbers of study volunteers; female and minority physicians represent a significant, untapped pool of PIs; and complaints filed with the FDA for non-compliance and fraud continue to rise.

Source: Tufts Center for the Study of Drug Development

These dynamics pose substantial management challenges for drug development sponsors that are aggressively seeking ways to improve site selection, volunteer enrollment, clinical study quality and efficiency, and regulatory compliance. This Tufts CSDD Impact Report builds on earlier studies that looked at the changing clinical investigator landscape. For more, see Tufts CSDD Impact Report 2007 Nov/Dec;9(6) and Tufts CSDD Impact Report 2005 May/June:7 (3).

Tufts CSDD Impact Report • page 2

Volume 11, Number 2 • March/April 2009

Available electronically or in hard copy format. To preview a complimentary issue of the Tufts CSDD Impact Report, email [email protected]. To subscribe, call 617-636-2170, email [email protected], or visit http://csdd.tufts.edu.

12

TUFTS CSDD EXECUTIVE FORUM ROUNDTABLES
An ongoing program of highly interactive, one-day roundtable discussions for senior R&D executives, hosted by the Tufts Center for the Study of Drug Development.

ROUNDTABLE I: Feb. 25, 2010

IMPROVING ROI AND LATE STAGE CLINICAL SUCCESS RATES
In an effort to boost ROI, many companies are looking to new operational strategies that leverage available data and improve Phase I and II design in an effort to maximize the likelihood of late stage clinical success. This roundtable will focus on different approaches taken by research-based large and small pharma and biotech firms to increase late stage success rates and boost ROI.

ROUNDTABLE II: May 13, 2010

STRATEGIES FOR MANAGING DRUG DEVELOPMENT RISK: MAINTAINING PORTFOLIO DIVERSITY
Across the pharma and biotech industry, companies are assessing strategies for managing risk in their development portfolios. Strategies range from new risk-sharing partnerships, to integrated network approaches to R&D, to an increased focus on targeted medicines development. This roundtable will examine company reviews of the obstacles and opportunities offered by these and other risk mitigating strategies..

ROUNDTABLE III: Sept. 16, 2010

OUTSOURCING STRATEGIES ACROSS THE VALUE CHAIN
Many companies have begun to reassess what they consider their core competencies. The result has been the evolution of a networked approach to pharma R&D, in which strategic partners provide critical capabilities along the entire value chain. In this roundtable, a presentation of Tufts CSDD findings on strategic outsourcing trends across the industry will be followed by specific examples of outsourcing strategies in both large and small pharma and biotech companies.

ROUNDTABLE IV: Nov. 4, 2010

STRATEGIES FOR OPTIMIZING THE DRUG DEVELOPMENT PROCESS: TRANSLATIONAL SCIENCE, NEW TECHNOLOGIES, AND CLINICAL DESIGN IMPROVEMENTS
The increasing size and complexity of clinical protocols is straining R&D budgets and extending development timelines. Translational science, however, has led to the introduction of new tools and technologies to improve the screening of candidate compounds and the design of clinical programs. This roundtable will focus on those tools and technologies that provide the greatest benefits and how companies have integrated them into their R&D activities.

All roundtables are held 10 a.m. – 4 p.m. at the Tufts Center for the Study of Drug Development in Boston. For more information, call Charlene Neu at 617-636-2187, or email [email protected].

Tufts Center for the Study of Drug Development
TUFTS UNIVERSITY

75 Kneeland St., Suite 1100 Boston, MA 02111 USA

Tel Fax Web

617-636-2170 617-636-2425 http://csdd.tufts.edu

Email [email protected]

OUTLOOK2010

Sponsor Documents

Or use your account on DocShare.tips

Hide

Forgot your password?

Or register your new account on DocShare.tips

Hide

Lost your password? Please enter your email address. You will receive a link to create a new password.

Back to log-in

Close