Developing and Marketing a

Blockbuster Drug
“Eli Lilly’s Experience with Prozac”
INTRODUCTION
• An antidepressant marketed in 1987

❖ First available drug in a new class of psychotropic drugs-

Selective Serotonin Reuptake Inhibitors

• Became biggest selling Blockbuster-drug

❖ Revolutionized the treatment of depression

INTRO (contd.)
• Effective: also allowed depressed to be treated by non
psychiatric physicians

• Increased the no. of patients who had access to

treatment

• Lowered cost of treating depression and other mental

illness
INTRO (contd.)
➔ Eli Lilly wanted to derive the lessons it could from its
experience with Prozac and apply those to new
potential Blockbusters:
● Symbyax
● Cymbalta

• Company convened several Prozac assessment

meetings
History of the Treatment of Depression
Prior to mid 19th century:
•Practitioners used herbal remedies while the afflicted
were turned out of homes and villages
•Asylum houses to deal with mentally ill
Towards mid 19th century:
•Psychiatry emerged as scientifically based profession
that studied the brain, seeking to understand the causes
of the disease and to discover new remedies
History of the Treatment of Depression (contd.)
End of 19th century:

•Psychotherapists believed that drug therapy is useless

and harmful.
o They only masked the symptoms of illness
History of the Treatment of Depression (contd.)
By 1960’s:
•More systematic methods were adopted

o Root of most mental diseases- alterations in brain

chemicals(neurotransmitters)

•Psychiatric community more focused on biological root of mental illness.

 Early drug therapies were rejected
History of the Treatment of Depression (contd.)
• Newer drugs were either • Modern therapy started with a
sedatives or hypnotics, effective major tranquilizer called
for calming patients but not for chlorpromazine(Thorazine)
impacting underlying illness

• Dissatisfaction with the existing

• Thorazine was remarkably
treatments led to search for
effective
drugs that could impact the
neurotransmitters

• Side effects made doctors and

patients reluctant to use it
History of the Treatment of Depression (contd.)
• Studies showed that psychotropic drug therapy could
avoid or shorten hospital stays, lessened use of electro-
shock treatment

• Miltown and Valium- two anti anxiety drugs were

introduced in 1950s and 1960

• These were effective safe and non sedating

Eli Lilly & Co.
Founded in 1876 by Colonel Eli Lilly
• Products were combination of plants and other natural ingredients

o First to ask feedback from physicians and hospitals on efficacy and safety of its
products.

• By the time he died in 1898 Eli Lilly was selling 2005 medical products with sales of
$332,979

 Eli Lilly collaborated with scientists at University of Toronto to develop insulin

and to design its intricate manufacturing process.
Prozac Development
• In 1970 Ray Fuller a senior a senior Lilly pharmacologist
followed a research.

• Low concentration of serotonin in the brain was linked to

depression
 Lilly was initially resistant

• It was extremely risky and the causes for the depression

were poorly understood
Prozac Development (contd.)
• Years of experience are required to study and develop
any drug

o Prozac is a first in class drug and it requires even

more time
Prozac Development (contd.)
Drug life
• Lab studies
 Impact with chemicals
 Impact with cells
 Animal testing
 Human testing

• Regulatory submittal
• Approval by FDA
• New dosage and forms(If the drug is successful)
• Patient behavior
• Patient expires and producers can still sell the drug(last phase)
Prozac Development (contd.)
Challenges in development
• Serotonin depression theories were too new
o Suicide was viewed as one of the side effects

• Psychiatric research on new neurotransmitters and brain receptors was very

new.
• Understanding mental illness proved to be very complex

• TCA type antidepressant called “Aventyl” failed in the market during 1960’s
• Difficult to market due to stigma associated with depression
Prozac Development (contd.)
Obstacles

•The pharmacology of the drug was poorly understood

•There was a medical misconception about the disease
•The market was poorly developed
Prozac Development (contd.)
• Lilly chemist Bryan Malloy had • 1985 German FDA refused to
synthesized some compounds to approve prozac
boost serotonin without side
effects of TCA
• 16 human trials attempted suicide

• 1974 lab results were positive

• Human trials were extended with
lower dosage

• Human research began in 1976,

but the first set of data did not
look promising
• Results were successful enough to
get FDA’s approval
Launching Prozac

•Why is Lilly doing this?

 We are an anti-biotic company why create a drug
for weak minded people?
Launching Prozac (contd.)
Education

•150 Psychiatric experts were invited

•Educate FDA
•Psychiatrists experience program
•Local market survey by sales Managers
•Convincing insurance companies
Launching Prozac (contd.)

• Prozac had the therapeutic advantage of enhancing only the effects of serotonin
• No tricky upward titrations like TCAs
• It was able to enhance the talk therapies
• Once a day dosing
• Prozac stayed in body longer than TCAs
• It was non lethal
Launching Prozac (contd.)
Launching Prozac (contd.)
Problems in launching

•Inability to predict the size of the market

o Cause for depression

 Off label uses

Launching Prozac (contd.)
• Launched in JAN 1988
• Wholesale price was $1.10 per day
• Retail price was $1.46 per day
• 48% > TCAs
• 4.5% above the highest priced antidepressants
• The company justified the price by its clinical advantage
 PROZAC’S SUCCESS ON THE MARKET
➔ Unlike previous medications, was physicians
reported Prozac true efficacy.

➔ First year sales were $130M and within 24

months, sales exceeded the total sales of all
antidepressants.

➔ Prozac quickly became the biggest selling drug in

history
PROZAC’S SUCCESS ON THE MARKET (contd.)

• Lilly’s Prozac sales allowed the company to maintain its

independence during 1990s, which were the tough years for
the pharmaceutical industry in general.

• In 1992, Prozac faced its first competition when other

companies started pouring new SSRIs on the market.

• Prozac transformed Lilly’s entire capabilities over the period

of its life.
PROZAC’S SUCCESS ON THE MARKET (contd.)

• Prozac’s marketing efforts include the usual print ads in

medical journals, drug sales force to call on doctors and
provide information, literature and free samples.

• Lilly also advertised Prozac to consumers in what was

called direct-to-consumer(DTC) advertising.

• Lilly added Prozac promotion by running DTC ads in both

print and broadcast media.
PROZAC BECOMES TOO POPULAR
Eventually two-thirds of Prozac prescriptions were made by
primary care physicians and only one-third by
psychiatrists.
•Medical journal reports reflected the high professional
enthusiasm for the drug.

•The press played a big role in hyping Prozac by creating a

media frenzy that had not been seen about a medical
product since the Salk polio vaccine.
PROZAC BECOMES TOO POPULAR (contd.)
• In 1993, Peter Kramer published the book Listening to
Prozac, prompting people with only mild problems to ask
for Prozac as well.

• Sales representatives told the company that it was

becoming difficult to look physicians in the eye when
talking about the drug.
Despite boon on sales, Lilly managers worried about the
consequences of excessive enthusiasm.
Backlash Against Prozac

Medical journal articles criticised side effects of SSRI treatment.

• Psychiatrists suspected akathesia-a drug induced agitation so extreme

could lead to violent behaviour or suicide.

Fuel to anti-psychiatry groups like Church of Scientology.

• Scientologists used their Citizens Commission on Human Rights (CCHR)
fighting for recall of Prozac.
Backlash Against Prozac (cond..)
In 1991, FDA convened an expert panel was formed to study and advise
FDA.

Based on unanimous finding FDA concluded that there is no scientific

evidence indicating that SSRIs were responsible for suicidal or violent
behaviour.

• In 2000, Psychiatrist Joseph Glenmullen published his book, Prozac

Backlash, Overcoming the dangers of Prozac, Zoloft, Paxil and Other
Antidepressants with Safe, Effective Alternatives.
Managing The Response
Media started printing suicide stories and Scientology
charges.

•Chuck Feehan, Prozac marketing research manager -

Lilly tried to reinforce that Prozac intended to treat a
serious disease among all the hype and negative press.
Managing The Response (cond..)
• 3 constituencies with which it communicated:
regulatory agencies, shareholders and physicians.

• It realized the need of public relations which resulted in

training the senior management people with talking to
press and media skills; responded well in bringing down
the criticism of Prozac.
Managing The Response (cond..)
• Regarding over-diagnosis and over-prescribing it educated the physicians
through proper data by training the sales people.

Chris Bodurow, Prozac Team Operations Manager said: “this crisis educated
the company to collect the data from various studies to prove our self right,
it will be evidence enough for the executive to speak with the press on their
comments.”

• Such evidences proven against Genmullen's book Prozac Backlash.

Managing The Response (cond..)
• Started working with patient advocacy groups to explore ways to undermine
the psychiatry attacks.

Because of these issues market share of Lilly predicted to have been 39% was
only 29% for the period of 1988-92; that difference amounts to $9 billion.
• Lilly managers learnt to responded to positive and negative reactions

• In addition to its other market projections, Lilly began conducting multiple-

scenario forecasting based on environmental conditions such as physicians
view on drug, potential stumbling blocks and sources of attacks.
Competition
• Prozac enjoyed 4 years of competitor free market, Once they came and used
the bad publicity of Prozac and they were aggressively priced and marketed.

o Two prime competitors GSK's Paxil and Zoloft.

• Lilly's Prozac settled as the best drug for the Psychomotor retarded depressed
patients. It closely studied its competitors.
Competition (contd.)
• Lilly decided to support head to head study comparisons with Paxil but in
one year Paxil sales grew as high as a $2.2 billion.

• In 2000 for the first time Paxil sales exceeds sales of Prozac, Paxil had
data to support its use in depression, anxiety, panic attack and a cluster of
symptoms with an indication allowed by FDA.
Lawsuits
• Side-effects
o Product-liability Lawsuits
 Two years in and the first lawsuit attacks
• 200 other lawsuits follow

• The two most popular and publicised trials

o The Wesbecker case and the Forsythe trial
 Lilly defended all the lawsuits until they were dropped, or dismissed or settled.

o All this negative publicity is suggested to have costed Lilly between $200 to $300
million in the year 1991 alone.
Loss of Patent Protection
• For a $3 billion drug like Prozac, daily revenue was above $8 million; 80%
of which would be lost in the generic rush

• The 90s was time of turmoil in the pharma industry; replete with
competition and financial troubles
o First-in-class drugs faced the stiffest competition from imitators

• Amidst a race for mergers and pipeline-marriages in an industry in

constant flux, Lilly chose to walk it alone.
Loss of Patent Protection (contd.)
• Year X Strategy
o Protect Prozac legally from generic manufacturers
o Patent-extension by introducing Prozac for childhood depression
o Market and patent new line extensions
o Support existing drugs
o Stoke product-pipeline and molecule-bank

• Barr Labs wins patent lawsuit against Lilly two years before its expiry and
all hell breaks loose
 Conclusion
• Perception and treatment of depression
o Marked Lilly’s foray into new markets and transformed it
 Lessons for gen-next drugs (Symbyax and Cymbalta)

• Symbyax and Cymbalta face a whole new environment, influenced by Prozac’s

history
o Would need to compete with branded and generic Prozac
o And face the same efficacy and safety concerns as Prozac

• GSK (Paxil) setback (for use in children) would influence reception for Symbyax
and Cymbalta
To Ponder Over
• Prozac was already widely prescribed by physicians for conditions other than
depression. So how effective/differentiated were the line extensions carried out
by Lilly (to increase Prozac sales) post patent expiration?

• Why did Lilly choose to wait out the critics' storm? Instea of taking the bull by its
horns? Was the waiting game a strategy or simply lack of expertise in handling
media attack?

• Involving patient advocacy groups in its educational campaign around Prozac

would have lent much more credibility and protection to Lilly. Its ad-campaigns
would have rung true in a whole new level; so why was this overlooked?
To Ponder Over
• How different/differentiated were the new generation descendants of Prozac
from their ancestor? In an already crowded generic market, what made Lilly
feel that Symbyax and Cymbalta had healthy prospects?

• Perseverance is definitely great, but Prozac was turned down seven times
before Lilly's management gave its go ahead. Why was research being carried
out for something deemed unfit (and that too seven successive times)? Is
there no mechanism to deal with organisational funding of projects, to ensure
efficient spending? R&D is the backbone of a pharma major; that being the
case, can Lilly afford blind spending sprees based on “hunches” and
“preferences”?
To Ponder Over
• What factors contributed to Prozac becoming a blockbuster drug?

• What difficulties can be expected in developing and marketing a

blockbuster drug like Prozac and how can these difficulties be addressed?