By submitting an electronic NDA, Isis believes it can shave at least a few months off the FDA's average 15-month review. "We think that we can get this through the FDA in a year," says B. Lynne Parshall, the company's chief financial officer. Isis's goal, of course, is to beat out its competitors and get Isis 2922 to the $200-million CMV retinitis market by the end of 1998 so that it can quickly begin to gobble up market share. The payoff could be enormous: just a month's worth of sales from Isis 2922 could more than cover the entire cost of the company's $300,000 computer system. More important, being first to market could be a key factor in making the company profitable.
Looking back on the launch of isis, CEO and founder Stanley T. Crooke admits that at first the company's prospects seemed especially bleak. "I don't think even I would have bet on us early on," says Crooke. In 1987 Crooke was the president of research and development for SmithKline Beckman (now Beecham), in Philadelphia. But traditional drug exploration was no longer satisfying Crooke's scientific appetite, and antisense drug technology, though new and untested, offered a potential giant leap forward in the fight against disease. With the help of a young scientist named David Ecker, Crooke began to experiment in the nascent field.
The two men soon discovered that SmithKline couldn't provide the resources needed to conduct a meaningful investigation into an entirely new category of drugs. The antisense experiments required more than just different scientific instruments, says Ecker; they had to be conducted by a different type of scientist. SmithKline had always hired chemists and biomedical engineers, who have a strong knowledge of the proteins that cause diseases. But the designers of antisense drugs need a deep understanding of RNA. "We were focusing on a totally different molecule," says Ecker. "And that meant we needed an entirely different workforce." So in 1989 Crooke and Ecker left the giant company and, with Daniel Kisner, a former vice-president of R&D at Abbott Labs, in Abbott Park, Ill., started Isis.
Crooke thrives on a challenge--though you'd never guess that from his appearance. He often comes to work dressed in a pink polo-style short-sleeved shirt and khaki shorts--proper attire given that it's balmy Southern California. But if you look beneath the surface, there are clear signs of a fierce competitor. For one thing, in spite of his delicate frame and admitted lack of vertical rise, Crooke is an avid basketball player--out on the courts daily. "I live to play the game," he says.
For a start-up in the pharmaceutical industry, however, the challenge isn't only about trouncing competitors; it's about creating a sturdy business and a cutting-edge scientific laboratory under one roof. And that takes as much knowledge of organizations as it does of organisms. Crooke has both. Glance at his bookshelves and you can't help but notice his ambidextrous expertise: Rosabeth Moss Kanter's The Change Masters leans up against archaic-sounding tomes like Advances in Prostaglandin, Thronboxane, and Leukotriene Research.
In the beginning Isis dove into identifying molecules that could become stable antisense drugs. By early 1991 Crooke had raised nearly $21 million in private placements and had already begun to see some optimistic lab results. The early success was enough to satisfy Wall Street, and in May of that year Isis went public, taking in close to $25 million. It was enough cash to begin clinical trials of five new drugs. Isis 2922 was the most promising.
Coordinating clinical trials is no easy task. For starters, test sites can be anywhere in the world, and each site generally handles between 20 and 1,000 patients. The process is long and involved because overwhelming amounts of data must be collected. Every time a patient in a study takes a shot or ingests a pill, which could be once a week or three times a day, the doctors and nurses on-site must record a slew of information about the patient's health. Everything from blood pressure to skin tone is written on a special case-report form, which is then delivered to the pharmaceutical company, where the information is entered into a database. For any given study, there can be as many as 100 or more pages per patient.
At Isis, those case-report forms typically arrive on Stuart Nixon's desk. He's the company's director of clinical-data management and biostatistics and the architect behind the company's data-management system. Nixon seems to embody the stereotype of a laid-back Californian, with his blond hair, startlingly blue eyes, Grateful Dead watch, and Jerry Garcia tie. But he is anything but far-out when it comes to processing data from the company's clinical trials. Nixon has set up a two-tiered system at the company: a massive document-management application called Optix, from Blueridge Technologies, to maintain a graphical record of the completed case-report forms, and a relational-database application called 4D, from ACI, to enable Isis's biostatisticians to analyze the data.
As soon as the case-report forms enter the building, a small army of data-entry operators quickly scans them into a Sun workstation as images and stores them in Optix. (They can't be scanned in as text because of the idiosyncratic nature of the compilers' handwriting.) The data-entry operators then keypunch the data from the images into the 4D database. Now biostatisticians can begin to manipulate and correlate the results from the studies using sophisticated statistical-analysis programs such as SAS, by the SAS Institute, and Axum, by MathSoft.
