25 Years of Biotechnology – Has it Met its Promise?

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6 Δεκ 2012 (πριν από 4 χρόνια και 7 μήνες)

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25
Years of Biotechnology


Has It Met Its Promise?

Gilad S. Gordon, MD, MBA

Disclosures

Consultant to:


Allos Therapeutics


Array BioPharma


Attenuon


GlobeImmune


Intarcia


Kinex


MetaBasis


OSI


QLT


Quark Pharmaceuticals

25
Years of Biotechnology


Has It
Met Its Promise?

Yes


Remarkable strides since human insulin approved in
1982


Cured some diseases


Improved quality of life for many


Clearly a mature industry with hundreds of drug
approvals

No


No clear drug products from Human Genome Project


No clear therapeutic path to individual genomic based
pharmacotherapy

Biotechnology History

1953


Structure of DNA defined


My parents get married

1957


Lord Todd wins Nobel Prize “for his work on
nucleotides and nucleotide co
-
enzymes”


I am born

1962


Watson and Crick win Nobel Prize


I enter Kindergarten

1974


Boyer and Cohen demonstrate the
expression of a foreign gene in bacteria


I apply to college

1976


Genentech, first biotech company is formed


Dr. Bill Haseltine is assigned as my tutor, I go pre
-
med

1978


First successful laboratory production of
recombinant human insulin


I take the MCATs

Biotechnology History

1980


Genentech goes public

1980


First human test of recombinant insulin


I begin second year of medical school

1982


Human insulin approved by FDA and
marketed by Eli Lilly under license from
Genentech


Senior year
-

I undertake studies on intra
-
nasal insulin
with future Dean Dr. Jeffrey Flier

1983


First monoclonal antibody test approved
for testing for Chlamydia Trachomatis


We graduate Harvard Medical School!


Biotechnology History

1985


Genentech receives FDA approval for
human growth hormone


first drug to be
marketed by biotechnology company

1985


Polymerase Chain Reaction (PCR)
technology developed

1986


Chiron receives FDA license for Hepatitis
B vaccine


first recombinant vaccine

1986


Muromonab
-
CD3 receives FDA approval
for reversal of acute kidney transplant rejection


first monoclonal antibody approved for therapy


I finish residency in Internal Medicine

Biotechnology history

1990


First gene therapy for ADA deficiency

1990


Jurassic Park published


public aware of risks

1991


UCSF and Stanford earn $40 million from
patents


changes way universities look at
biotechnology

1991


Alglucerase approved to treat Gaucher’s
disease

1997


First cloned sheep
-

Dolly

1997


Rituximab receives FDA approval


first
antibody based treatment for cancer (non
-
Hodgkin’s
Lymphoma)

2000


Human Genome mapped

Biotechnology Companies (
2006
)

Companies

Public

Total

Revenue*

Net Loss

Research and
Development**

# employees

United States Worldwide

336



710

1452



4275

$
55.4
B


$
73.5
B

$
3.5
B



$
5.4
B


$
22.8
B


$
27.8
B

130
,
600


190
,
500

*
52
companies are profitable

**For comparison:
2006
NIH Budget
-

$
28.7
B

Ernst & Young,
2007

Biotechnology today

2000

3
biotech product categories with over $
1
billion
in sales out of
36
total products with over $
1
B in
sales

2006

18
biotech product categories with over $
1
billion per year in sales out of
101
total products
with over $
1
B in sales

10
biotech product categories with over $
2
billion in sales out of
36
total products with over
$
2
B in sales


New Biotech Drug and Vaccine Approvals/
New Indication Approvals by Year


New Biotech Drug and Vaccine Approvals/ New Indication Approvals by Year







Bio,
2007

Top
10
Biotechnology Proteins

Drug

Human insulins (diabetes)*

Epoetin alpha (anemia)*

Etanercept (arthritis)

Darbopoetin (anemia)*

Rituximab (NHL)

Infliximab (Crohn’s, arthritis)

Trastuzumab (breast cancer)

PEG
-
filgrastim (neutropenia)*

Bevacizumab (colon cancer)

Adalimumab (arthritis)


* ”Replacement therapy”



2006
Sales

$
7.8
B

$
6.1
B

$
4.4
B

$
4.1
B

$
3.9
B

$
3.6
B

$
3.1
B

$
2.7
B

$
2.4
B

$
2.0
B

Ernst & Young, 2007

Major Challenges

Complexity and costs of clinical research

FDA policies

Pricing

Financing


Phases of Clinical Research

Phase I


50
-
100
patients


First in Man


Dose escalation


Define Maximum Tolerated Dose

Phase II


200
-
1000
patients


Early efficacy trials


Define therapeutic dose


Define study population



Phases of Clinical Research

Phase III


500
-
5000
patients


Large clinical trials


Define safety and efficacy in target population


Define limitations of drug

Phase IV


thousands of patients


Post
-
approval


Better define safety


Identify other target populations

Clinical Research

Timelines and Costs

Overall costs


discovery to approval


Time: 4
-
14 years


Costs:

$30
-
$200 million

Over $800 if amortize costs of failed drugs


Number of patients:

Minimum 500 for rare disease or unmet medical
need

5,000 for drug for common disease, i.e. arthritis

Over 60,000 for recent vaccine for RSV

Clinical Research


Ongoing challenges


Access to patients


Access to investigators


Availability of research personnel


Location of research

United States

Developed world

Under
-
developed world


FDA Policies

Overall, fewer new drug approvals

Balance of off
-
label use vs. restriction on off
-
label use

Balance of safety vs. demand for new
therapeutics


Currently weighted towards safety


Increased need for post
-
marketing safety studies


Demand for increased size of trials to demonstrate
safety

What is role of generic proteins, i.e. bio
-
similars?


Costs of Treatment of Colon
Cancer

1996


Total costs of drugs:


$
500


Expected median survival:

11
months


2007


Total costs of drugs:


$
250
,
000


Expected median survival:

24
months


IS TREATMENT WORTH $
20
,
000
PER
ADDITIONAL MONTH OF LIFE?

Ernst & Young
2007

Pricing

What is a fair price?


Company perspective

“Appropriate” return on investment to investors

Assure future investments in the field

Comparable pricing to “similar” products

Favorable cost
-
effectiveness analyses

Drug costs are still less than
10
% of total costs of
healthcare


Public health perspective

Can payers afford $
500
to $
35
,
000
(Eculizumab for
PNH) per month?

Is this price
-
gauging?

Should prices be based on “cost of goods”?

What is the “value” of the drugs?

Why are prices lower in other countries?

Pricing
-

Response of Payers

Governments


develop cost
-
effectiveness guidelines for
drug pricing approval


UK


Rejected use of bortezomib, bevacizumab, and cetuximab
based on price


Australia


Rejected use of Human Papillomavirus Quadrivalent
(Types
6
,
11
,
16
, and
18
) Vaccine, Recombinant based on price

Local Payers


Strict criteria on who gets drug

Insurance companies


Increase co
-
pays

Individuals


Decision to forego therapy


Overall, should there be a “pricing policy” and what
would be its implications?


Financing Sources

Government

Venture capital

Partnerships

Public markets



Additional Challenges

Basic research

Pre
-
clinical research

Intellectual property

Pharmacogenomics

Individual therapeutics


Early Stage Research

Basic research


Harder to justify in corporate world


role of NIH


Who will fund?

Pre
-
clinical research


Most active area of research


Need to define more appropriate pre
-
clinical efficacy
models


Need to define more appropriate toxicology models



Intellectual Property

How to protect Intellectual Property?


Role of Universities


Changing rules


“first to file” vs. “first to
invent”


Value of IP in developing countries

Pharmacogenomics

How to integrate human genome knowledge?


How to translate findings of the human genome into
population based therapeutics?

How to determine if specific DNA mutations cause disease?

How to develop therapy for different mutations in different
genes which cause the “same” disease?

How to treat different mutations in the same disease
-
causing
gene?

How to develop specific therapeutics for specific DNA
mutations?


Population
-
based genotype databases?

Critical to understand disease, the effect of therapeutics, and
the safety of therapeutics?

How can one preserve confidentiality in age of “insurance
discrimination”?


Individual Therapeutics

How to develop individual therapeutics?


Can genotype differences predict response to
a therapeutic?

i.e different responses amongst African
-
Americans
to isosorbide dinitrate/hydralazine for heart failure


How to develop drugs for individual patients

The ultimate holy
-
grail of medicine!

Requires change in paradigm of FDA review


Are there valid “pre
-
clinical” models that can be used?


Need to focus on individual efficacy vs. population based
safety and efficacy



25 Years of Biotechnology

From Human Insulin to Today….….

Industry is certainly mature

Hundreds of drugs approved

Many patients have benefited

Challenges remain

Overall


promise of the new technology of
1983
has largely been met and even
exceeded!


The Future…………….