The Drug Development

Process

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Key facts

•Research and Development

Time to develop a drug = 10–15 years

•Development Costs:

–Cost to develop a drug

2001 = $802 million2

1987 = $318 million

1975 = $138 million

–Cost to develop a biologic

2006 = $1.2 billion

R&D Spending

Percentage of Sales that went to R&D in 2006

Domestic R&D as a percentage of domestic sales= 19.4%

Total R&D as a percentage of total sales = 17.5%

Total National Institutes of

Health Funding(Part of this budget is allotted for developing

drugs.)

• 2007 = $28.6 billion

• 2006 = $28.5 billion

• 2005 = $28.7 billion

Approvals

• Drugs approved in 2006 = 299

• Only 3 of 10 marketed drugs ever produce

revenues that match or exceed R&D

costs.

• Between 1995 and 2005, over 160 orphan

drugs were approved.

• Average effective patent life for

pharmaceuticals= 11.5 years

Value of Medicines

• New medicines generated 40 percent of the two-year gain in life expectancy achieved in 52 countries between 1986 and 2000.

• A recent study found that the return on investment (ROI) for a 20 percent increase in adherence was substantial for disease-related costs: for every $1 spent on diabetes medicines, there were $7.10 in savings; the savings for $1 spent on cholesterol medicines was $5.10; and, for every $1 spent on blood pressure drugs, $4 in savings resulted.

• Every additional dollar spent on health care in the United States over the past 20 years has produced health gains worth $2.40 to $3.

Sales

• Total number of U.S. prescriptions

October 2004 September 2005

$3.6 billion

• Generic share of market by volume

(generic/brand, weighted average)

– July 2005 = 54/46

– 2006 = 58/42 (estimated)

“There’s nothing more innovative than

working in the pharmaceutical industry

right now. There’s nothing more

exploratory. There are no frontiers that are

more open than those that exist in our

business right now.”

—Andrew Dahlem, Ph.D., Eli Lilly and

Company, Vice President, Toxicology/

Drug Disposition and

Pharmacokinetics

BiopharmaceuticalCompanies Are Investing

More in Research and Development

Sources: Burrill & Company, analysis for Pharmaceutical Research and Manufacturers of America, 2007; and Pharmaceutical

Research

and Manufacturers of America, PhRMA Annual Member Survey (Washington, DC: PhRMA, 2007).

*The “Biopharmaceutical R&D” figures include PhRMA research associates and nonmembers; these are not included in “PhRMA

Member Companies’ R&D Expenditures.” PhRMA first reported this data in 2004.

The Cost of Innovation

• Developing a new medicine is a long and costly process. The chances of success are very low.

• There are many estimates of the cost of developing a drug, but one of the most-cited studies is from the Tufts Center for the Study of Drug Development, which put the average cost of developing a new drug at $802 million (in year 2000 dollars), including the cost of failures and capital.

• The Tufts Center also recently estimated the cost of developing a biologic (a medicine generally composed of large and complex molecules, produced by a biological system) to be $1.2 billion (in year 2005 dollars).

Most Leads Don’t Become

MedicinesStatistics show that most candidate drugs

never make it to the medicine cabinet. In fact:– Only 1 in 5,000–10,000 compounds tested

eventually reaches consumers.

– Only 1 of every 5 compounds that enter clinical testing reaches the market.

– Only 3 of 10 drugs that reach the market ever earn enough money to match or exceed the average R&D cost per new medicine.

Drug Development Costs

Note: The Tufts Center for the Study of Drug Development has updated its $802 million estimate

by adjusting for annual rate of R&D

increases and inflation. That estimate is available at http://csdd.tufts.edu/.

Source: J. A. DiMasi, “Tufts Center for the Study of Drug Development Pegs Cost of a New

Prescription Medicine at $802 Million,”

press release, 30 November 2001.

The New Drug R&D Process

10-1

5 y

ears

Pre-Discovery

• Understand the Disease to be Treated.

What are its causes, molecular pathways, and

effects?

• Identify a Drug “Target.”

What gene or protein should the new drug affect?

• Test the Target for Research Feasibility.

Is the target really involved in the disease process?

Can a drug act on the target?

Drug Discovery

Find a Candidate Drug or “Lead.”What molecule may act on the target to change disease

course?

Conduct Initial Tests on Every Promising Compound.– Is the compound nontoxic?

– Can it be absorbed into the bloodstream?

– Distributed to the proper site in the body?

– Metabolized?

Optimize Remaining Leads for Safety and Effectiveness.Are any of the hundreds of possible chemical variations

of a lead more effective against the target or less toxic?

Pre-clinical

Test Leads in the Laboratory and in Animals.

How does the candidate drug work?

Is it safe enough for testing in humans?

Develop and Test Process to Make Drugs for

Clinical Trials.

What “recipe” and form should it have forhuman

use?

How can we make enough of the drug forpatient

testing?

IND Application and Submission

File an Investigational New Drug (IND) Application with the Food and Drug Administration (FDA).

– What is the new drug’s chemical structure?

– Mechanism of action?

– Side effects?

– What is the research plan for clinical trials?

FDA and IRB (Institutional Review Board) Reviews

– Are risks to clinical trial participants reasonable?

– Are plans for informed consent and monitoring/reporting adequate?

Clinical trials

Conduct Phase I Trials (20–100 healthy volunteers).– Is the candidate medicine safe in humans?

– How is the drug metabolized by the body?

– What is the safe dosing range?

– Should it move into further development?

Conduct Phase II Trials (100–500 volunteers with the target condition).– Does the drug improve the patients’ condition?

– What are its side effects?

– Does it have the anticipated mechanism of action?

– What are the most safe and effective doses and dosing schedules?

Conduct Phase III Trials (1,000–5,000 volunteers with the target condition).– Does the drug show statistically significant safety and benefit?

– Is the medicine safe over time?

FDA Review

Submit New Drug Application (NDA), which includes up to 100,000 pages of information on research findings, analysis of clinical trial results, and proposed labeling and manufacturing plan.–Is the new drug safe and effective enough to be

approved for use?

–Are more studies or information needed before a decision can be made?

–Does the proposed manufacturing process ensure product safety and integrity?

Large-Scale Manufacturing

Create and Perfect a Large-Scale Manufacturing Process.–How can we move from smaller-scale production to large

quantities of labeled, packaged products ready for distribution?

–How can we guarantee that each tablet will contain the correct amount of the drug without impurities?

–How can we ensure manufactured product safety?

Create a Customized Manufacturing Facility.–Is a new facility needed, or can an existing facility be

adapted?

–Does the manufacturing facility comply with good manufacturing practices set out by the FDA?

Create a (Sometimes Global) Distribution Process.

Innovative Approaches Characterize New

Medicines in Development

Orphan Drugs Advance

Treatment for Rare Diseases

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