Eli Lilly leveraging Prozac success into New Drug Developments

By Thomas M. Burton
Staff Reporter of The Wall Street Journal
Eli Lilly & Co. shot to the forefront of psychiatric therapy principally through one big drug, Prozac, the world's leading antidepressant. But now, Prozac faces tough competition, and its main U.S. patent protection expires in five years.
Was Lilly's mental health-research program a one-drug wonder?
To try to ensure that it isn't, the company is devoting a monumental amount of money and effort to the search for other drugs for disorders of the brain and central nervous system. There are no guarantees: Nine of 10 drugs fail in clinical trials, and the research competition is tough. But Indianapolis-based Lilly is on the short list of companies that analysts and psychiatrists regard as most likely to produce the next generation of blockbuster psychiatric drugs.
"There's no question Lilly is in the forefront of research on central-nervous-system receptors," says medical-industry analyst Hemant K. Shah, referring to those key portions of the brain's electrical circuitry that control much mental activity. Glaxo Wellcome PLC and Pfizer Inc. are among competitors often cited as also among the leaders in CNS drug research.
Lilly's CNS research program in recent years has commanded about a third of the company's annual research and development budget, which hit $1.04 billion last year. Up to 15 mental-health drugs are in development at any given time nowadays, about twice the figure from 10 years ago. Scientists in the program are evaluating compounds for schizophrenia, pain and migraine, Alzheimer's, anxiety and depression, stroke, spinal-cord injury, Parkinson's, sleep disorders, alcoholism, obesity, and smoking cessation. Some analysts are predicting that Lilly's drug Zyprexa for schizophrenia will be the next big psychiatric blockbuster drug if it receives expected federal marketing approval this year.
And Prozac, with $2.3 billion in annual sales predicted this year, is the financial and scientific fuel propelling Lilly's mental-health research. Sales of Prozac grew 24% in 1995, to $2.07 billion, and made up nearly a third of Lilly's total yearly sales of $6.76 billion. Total sales for 1995 were up 18% from 1994. Earnings from continuing operations in 1995 were $1.31 billion, or $2.30 a share, up from $1.19 billion, or a split-adjusted $2.05 a share, the year before.
Prozac profits, quite literally, paid for the 620,000-square-foot red granite-and-limestone research facility, called Building 48, that houses this research. Prozac paid, too, for many of the top neuroscientists who work there. And the knowledge of how Prozac works has provided Lilly researchers with the scientific foundation for current forays into the intricate workings of the brain and spinal cord.
"CNS research is a game of probabilities. If you have a lot going on, the probability of one compound becoming a breakthrough drug is higher," says Steven M. Paul, head of CNS research and vice president of Lilly Research Laboratories. "We have lots of things going on, and we believe the chance of one of our compounds becoming a blockbuster drug is pretty good."
Colleagues credit Dr. Paul, 45 years old, with much of the division's promise. A premier neuroscientist and formerly scientific director of the U.S. National Institute of Mental Health, he was lured to Lilly in 1993. Other Lilly researchers describe him as instrumental in recruiting top scientists from academia and in lobbying internally for more research funds.

Lilly's Central Nervous System Drugs


Prozac Marketed
DISEASE: Depression; Obsessive-compulsive disorder

Permax Marketed
DISEASE: Parkinson's

Zyprexa Awaiting possible FDA approval
DISEASE: Schizophrenia

Duloxetine Phase II (clinical trials)
DISEASE: Urinary incontinence; Depression

Xanomeline Phase II
DISEASE: Alzheimer's

LY303870 Phase II
DISEASE: Pain, migraine

LY300164 Phase I (clinical trials)
DISEASE: Epilepsy

LY320236 Phase I
DISEASE: Enlarged prostate; Prostate cancer

LY156735 Phase I
DISEASE: Sleep disorders; Circadian rhythm disturbance
such as jet lag

LY334370 Phase I
DISEASE: Migraine

LY354740 Phase I
DISEASE: Anxiety; Smoking cessation

LY293558 Preclinical

LY306541 Preclinical
DISEASE: Attention deficit hyperactivity disorder