The Lifecycle of a Drug:
Pharmaceutical Advertising,
Patent Extension,
& Me-Too Drugs
©PharmedOut 2013
Georgetown University Medical Center
Part of the Drug Ads Exercise Presentation Series
Disclaimer: Intellectual Property
In this presentation, you will notice that we use images of
many registered trademarks, many branded drug trade
names, and many copyrighted advertisements -- from many
different business concerns -- including drug companies,
marketing consultants and medical journals. All of the
intellectual property contained therein is, and remains, the
exclusive intellectual property of the respective owners.
Each image is used for the purpose of educational, and
critical, analysis. No endorsement of any position articulated
in this presentation should be inferred from the appearance
of any brand, trademark, trade name or ad copy herein. This
presentation has been designed with the intent to qualify
for the doctrine of "fair use" -- as to these pieces of
intellectual property -- under the law of the United States.
Pharmaceutical Advertising
Marketing Timeline
1. Pre-Launch Ads and Disease/Mechanism
Mongering
2. Launch
3. Active Marketing
Marketing Timeline
1. Pre-Launch Ads and Disease/Mechanism
Mongering
2. Launch
3. Active Marketing
Pre-Launch: “Coming Soon”
Pre-launch ads:
• Pique interest in a new product
• Introduce logos and color schemes
• Introduce the brand name
PRE-LAUNCH

LAUNCH

ACTIVE MARKETING

Marketing Timeline
1. Pre-Launch Ads and Disease/Mechanism
Mongering
2. Launch
3. Active Marketing
Launch
Launch:
• Announcement of availability
LAUNCH
PRE-LAUNCH


ACTIVE MARKETING

Marketing Timeline
1. Pre-Launch Ads and Disease/Mechanism
Mongering
2. Launch
3. Active Marketing
Active Marketing
Ads now include:
• Brand name
• Generic name
• Use/indications
• Summary of side effects
• Contraindications
• Effectiveness
ACTIVE MARKETING
PRE-LAUNCH

LAUNCH


Patent Extension
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Delayed-Release Preparations
• Controlled-release (CR)
• Sustained-release (SR)
• Extended-release (XL)
• Long-acting (LA)
Ambien CR
(Controlled-Release)
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Patient extension may be granted
for minor changes in dosing.
Examples:
• Yasmin (ethinyl estradiol
30 mcg / drospirenone 3 mg)
• Yaz (ethinyl estradiol
20 mcg / drospirenone 3 mg)
• Androgel (topical testosterone
1% vs. 1.62%)
Aricept
(for Alzheimer’s Disease)
•
To extend patent life on Aricept, the manufacturer
developed a 23 mg version.
•
Aricept 23 mg failed to show a statistically significant
improvement over the previously approved Aricept 10
mg formulation in both primary and secondary
outcome measures.
•
Aricept 23 mg demonstrated a higher incidence of
adverse events such as nausea, vomiting, diarrhea,
anorexia, and fatigue.
Aricept 23 mg: Approval Granted
Aricept 23 mg was approved, despite a lack in
superiority over Aricept 10 mg and
recommendations of non-approval by two
FDA medical reviewers.
Aricept 23 mg: Approval Granted
Justification of FDA approval:
“The 23 mg dose is clearly superior to the 10 mg
dose on the cognitive measure. In my view, this
strongly argues for a conclusion that the 23 mg
dose is very likely to also have an effect on overall
functioning, despite this not having been
demonstrated directly in this study.”
- Dr. Russell Katz, Division Director, Neurology
Products
“Aricept 23 mg… did not show improvement on overall patient
functioning. In the study, more people who took Aricept 23 mg
experienced increased side effects.”
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Fixed-Dose Combinations
• Fixed-dose combination: two or more
drugs in one pill.
• Fixed-dose combinations:
• Are often more expensive than their
components.
• Provide less flexibility in dosing options.
Fixed-Dose Combination: Example
•
Fosamax plus D (Vitamin D), a bisphosphonate, is patentprotected and costs six times as much as its generic,
alendronate.
•
Bisphosphonates must be taken with a calcium
supplement. However, calcium supplements are often
formulated with Vitamin D.
•
Since a patient must still take additional calcium with
Fosamax plus D, the total tablet burden remains the
same.
•
Therefore, the “plus D” component is of no use beyond
marketing the product.
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Enantiomers: Definition
• Many drugs are a racemic mixture, containing equal parts
of the left-handed and right-handed enantiomer.
• Receptors may only accept one enantiomer. Effectively
one-half of the drug molecules in a racemic drug are
active and the other half are inactive.
• Left-handed enantiomers of drugs use
the prefix “es” or “levo”
• Right-handed enantiomers of drugs use
the prefix “ar” or “dextro”
Enantiomers: Definition
1. It has become common practice to introduce
a drug as a racemic mixture.
2. Then, when the patent is close to expiring,
the company releases the active enantiomer
as a “new, improved” product.
Ask yourself: Why is the racemic mixture
marketed first when it was technically
possible to market the active enantiomer
initially?
Omeprazole
(Patient Care, 2000)
Esomeprazole
(JAMA, 2005)
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
Metabolites, Prodrugs, and Analogs
Although there are exceptions, many
metabolites, analogs, and prodrugs have no
advantages over the originator drug.
Example:
Desloratidine (Clarinex) is the main metabolite
of loratidine (Claritin).
There is no evidence that desloratidine is
superior
Vyvanse (for ADHD)
• Vyvanse (lisdexamfetamine)
is dextroamphetamine linked
to a lysine molecule,
allowing for it to be cleaved
to its components upon
ingestion.
• While this allows for peak
doses to be reached earlier,
there is no advantage to this
and could theoretically
increase rates of adverse
effects.
Strategies for Patent Extension
• Delayed-release preparations
• Minor changes in dosing
• Fixed-dose combinations
• Enantiomers
• Metabolites, prodrugs, analogs
• Renaming
The Rename Game
• A new indication can extend the patent life of a
drug.
• Some drugs are renamed upon approval for a
new indication, allowing for patent extension.
Bupropion =
=
=
= Sildenafil
The Rename Game: Example
=
Example:
• Fluoxetine is the generic version of both Prozac and Sarafem.
• After Prozac lost patent exclusivity, Sarafem provided new life
to the patent.
• Fluoxetine could only be substituted for Prozac, NOT Sarafem,
because the indications for which the drugs were approved
were different.
• Now that Sarafem has lost patent exclusivity, both drugs are
available as generics.
Me-Too Drugs
Me-Too vs. First-In-Class Drugs
• First-in-class drugs are novel drugs.
• Me-too drugs are similar, related
drugs to first-in-class drugs.
• Marketing may exaggerate the
benefits of a me-too drug versus the
original first-in-class drug.
Me-Too Drugs
• A me-too drug could be better than
a first-in-class drug, or it could be
worse.
• Example: Simvastatin, a me-too
drug, is a more effective statin than
lovastatin, a first-in-class drug.
Graphic reprinted by permission from Pill Advised.
• On the other hand, Baycol
(cerivastatin) was withdrawn from
the market due to a
disproportionate number of cases
of rhabdomyolysis.
NEJM, January 1999
NEJM, January 2001
“Rare cases of rhabdomyolysis
“Cases of rhabdomyolysis
have been reported with
cerivastatin”
have been reported with
cerivastatin”
Baycol was withdrawn from
the market in August 2001
due to excess cases of rhabdomyolysis.
Me-Too Drugs:
Marketing Messages
• Increased potency or longer duration of effect
• Faster onset of action
• Fewer unwanted effects
• Improved receptor selectivity
• Conversely, first-in-class drugs may market their
longer history and larger body of research
Me-Too Drugs:
Marketing Messages
• Increased potency or longer duration of
effect
• Faster onset of action
• Fewer unwanted effects
• Improved receptor selectivity
Increased Potency or
Longer Duration of Effect
• May add no clinical benefit
• May increase the risk of adverse events
• May increase flexibility in dosing options
Me-Too Drugs:
Marketing Messages
• Increased potency or longer duration of
effect
• Faster onset of action
• Fewer unwanted effects
• Improved receptor selectivity
Faster Onset of Action
In chronically used drugs, such as statins,
faster onset of action would only affect the
first dose.
Me-Too Drugs:
Marketing Messages
• Increased potency or longer duration of
effect
• Faster onset of action
• Fewer unwanted effects
• Improved receptor selectivity
Fewer Unwanted Effects
• Unwanted effects take time to be
discovered and reported.
• Pre-market studies cannot pick up longterm adverse effects, drug interactions, or
effects that occur only in elders, diabetics,
or other subpopulations.
• Claims of increased safety for new drugs
are not trustable without long-term data.
Me-Too Drugs:
Marketing Messages
• Increased potency or longer duration of
effect
• Faster onset of action
• Fewer unwanted effects
• Improved receptor selectivity
Decreased Risk for
Drug Interactions
Molecular stories, such as improved receptor
selectivity, may not necessarily have a clinical
benefit.
To properly assess a me-too drug, adequate
controlled studies with patient-oriented
endpoints in relevant populations are
required.
Ask yourself: Does treatment with the metoo drug result in the patient living longer or
better?
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