The Product Pipeline and Clinical Trials: Bringing a Drug to Market
September 6 and 8, 2005


Readings and Other Activities: NEW:Drugs in '05: Much Promise, Little Payoff

1. Clinical Trials from CenterWatch Clinical Trials
2. Orphan Products: Hope for People With Rare Diseases FDA Consumer, 2003
3. Be sure to 'interact with' the FDA's
New Drug Development Process (click on any button or phrase on diagram for more info)
4. Biotech 101: The Road to FDA Approval: Adam Feuerstein, TheStreet.com, July 5, 2004
Science 29 July 2005: Special Issue on Drug Discovery
5. 29 July 2005: Sending Pharma Better Signals;
6. 29 July 2005: The Hunt for a New Drug: Five Views From the Inside;
7. 29 July 2005: Productivity Counts--But the Definition Is Key


How does a drug candidate (recombinant or otherwise) get through the federal regulatory processes and finally make it to market?

(Note: a PDF) "The Century of Biology Begins with 369 Biotechnology Medicines in Testing for More Than 200 Diseases: By using the body's own tools and weapons to fight disease, pharmaceutical and biotechnology companies are developing more and better medicines. A survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) found 369 medicines in the pipeline that meet the definition of "biotechnology medicines": they use proteins and other substances produced in the human body to counter disease. All together, the biotechnology medicines in the pipeline target more than 200 diseases."


I. Steps in the Product Pipeline:

1. Discovery Research: ($155-225 M), ~ 5.5 years!!!

2. Pre-clinical: ($65M - $90M) ~ 4 years!!

3. File an IND to the FDA: If the company or laboratory decides to pursue human studies, it must first submit an Investigational New Drug application to the FDA for approval. The FDA's Center for Drug Evaluation and Research (CDER) reviews the IND, and The Center for Biologics Evaluation and Research (CBER) regulates biological products.

Next Step: Clinical Trials: testing experimental drugs in humans.

4. Phase I clinical trials (~$10 M or more)

5. Phase II clinical trials (~$25 M- $35 M)

6. Phase III clinical trials (often $100 M or more!)

7. File an NDA with the FDA: The FDA must review all drugs and clear them for marketing, mandated by the Prescription Drug User Fee Act (PDUFA), a law passed in 1992 that allows the FDA to charge drug companies a fee for reviewing their NDA / BLA.

8. Phase IV trials: Conditional approval after the drug or treatment has been marketed...


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Some variations on the basic theme...

1. Speeding things up: Since 1997, the FDA has been approving drugs at almost twice its usual rate (6 months rather than 10 months), thanks in part to money provided by the drug industry to speed the drug review process.

2. Compassionate Use: An alternative to clinical trials for desperately ill patients.

3. The Orphan Drug Act of 1983,

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Misc:

Who can conduct clinical trials and who pays for clinical trials? (go to link)

Informed consent (information from link)

"The process of learning the key facts about a clinical trial before deciding whether or not to participate.

Who can participate in a clinical trial (inclusion and exclusion criteria)? (information from link)

Something to keep in mind when and if you become an MD...the best physicians keep themselves aware of the clinical trials at their Medical Center and at those in surrounding areas. This could mean the difference between life and death for patients who qualify, and as well, further the cause of scientific knowledge needed to bring a new drug to market.

Clinical Trials program at Indiana University School of Medicine
Center Watch Clinical Trials Listing - anything appeal to you?

Should Drug companies post BOTH their positive and negative results of clinical trials?

Two Studies, Two Results, and a Debate Over a Drug New York Times, June 3, 2004
Merck Says It Will Post the Results of All Drug Trials New York Times, Sept 6, 2004

Check the news this coming week about a House subcommittee about publishing unfavorable clinical trial results.

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II. Timelines!

FromThe Drug Development and Approval Process : It takes 15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.

 

Early Research
/Preclinical Testing

File
IND
at
FDA

Clinical Trials

File
NDA
at
FDA

FDA

 

Phase
IV

Phase
I

Phase
II

Phase
III

Years

6.5

1.5

2

3.5

1.5

15
Total

Additional
post-
marketing
testing
required
by FDA

Test
Population

Laboratory and animal studies

20 to 80
healthy
volunteers

100 to 300
patient
volunteers

1000 to 3000
patient
volunteers

Review
processs/
approval

 

Purpose

Assess Safety and biological activity

Determine
safety
and
dosage

Evaluate
effectiveness,
look for
side effects

Confirm
effectiveness,
monitor adverse
reactions from
long-term use

Success
Rate

5,000 compounds evaluated

5
enter trials

1
approved

From Overview Of The Hatch-Waxman Act And Its Impact On The Drug Development Process

[Image]

ANDA = "Abbreviated New Drug Approval - is used by potential manufacturers of a generic copy of a previously approved drug. Once approved as bioequivalent (comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use), an applicant may manufacture and market the generic drug product." (Can't go here, but...Discount Drug Plan Announced: "Ignoring a federal ban on prescription drug imports, Gov. Rod Blagojevich announced Tuesday, Aug 17, that the state of Illinois is creating an online clearinghouse of pharmacies to help Illinois residents purchase drugs from Canada, Ireland and the UK" .

Indicting the Drug Industry's Practices
New York Times, Sept 6, 2004 Ouch!
A scathing attack on the implications of the Bayh-Dole Act of 1980 that changed the way university discoveries could be patented, and how "patent shenanigans have reshaped the drug business". More on this when we talk about Tech Transfer on 9 Nov !

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IV. A few notable pipelines:
Some of the drugs in these pipelines will go on to become huge winners, while others will crash and burn! Note: BEWARE the WAYYY over-used term ROBUST (as in 'robust pipeline'). Sounds great to investors, but it is a pretty data-less adjective!

Compare:
Amgen (Nasdaq: AMGN)
Biogen (Nasdaq: BGEN)
Chiron (Nasdaq: CHIR)

Genentech (NYSE: DNA)
Medimmune (Nasdaq: MEDI)

With:
ICOS, (Nasdaq: ICOS)
Celera Genomics (NYSE: CRA)
Exelexis (Nasdaq: EXEL)
Human Genome Sciences (Nasdaq: HGSI)
Millennium (Nasdaq: MLNM)


V. Feeling LUCKY? If you had money to invest in one of these companies, which would YOU pick, and why?? That's our next topic!!!


Objectives:

1. For each stage of the Drug Developmant and Approval Process, be sure to know how many years, how much $$, and how many patients (where applicable) would be involved at each stage.
2. Distinguish between an IND and an NDA
3. Explain the three process that can speed up FDA approval. .
4. Describe compassionate access and when it is used.
5. Explain the Orphan Drug Act, why it was implemented, and how it provides an incentive to pharmaceutical companies.
6. Distinguish between inclusion and exclusion criteria for a clinical trial.