A Different Approach to Drug Discovery

Article excerpt

During the past decade, most large pharmaceutical firms have seen their drug pipelines decline. But Novartis AG, headquartered in Basel, Switzerland, has a different tale to tell. Last year, it received approval for four new drugs. The company has about 50 new medications in late-stage clinical trials and roughly 90 in its early-stage pipeline. A major reason for that success: a new philosophy of drug discovery.

The philosophy driving Novartis's recent drug development efforts isn't focused on creating the next blockbuster treatment for high cholesterol. Rather than pursuing the kind of surefire blockbusters that have characterized the pharmaceutical industry, Novartis's process focuses on the unmet medical needs of smaller groups of patients. Medical researchers work in a research organization that reports directly to the CEO. And the CEO and board of directors are committed to maintaining the culture that's produced the company's robust drug pipeline.

Instead of working with marketers from the earliest stages of discovery, scientists in the eight-year-old Novartis Institutes for Biomedical Research (NIBR) collaborate with doctors who treat actual patients. NIBR researchers at the Cambridge, Massachusetts, headquarters and eight other locations worldwide also seek medications that treat fewer patients than the traditional blockbusters. Compensating for the lower sales of each new drug is the set of insights gained in the efforts to treat less well-known diseasesinsights that can lead to yet more drugs.

Those insights stem in large measure from a scientific approach to drug discovery that focuses on molecular pathways. That focus is particularly relevant to understanding the causes of several rare genetic disorders. These are the diseases that large pharmaceutical companies generally ignore because they involve few patients and hence have little revenue potential.

"Our focus is on the patient and trying to meet unmet medical needs," says Dhaval Patel, head of NIBR Europe. "That's easy to say, but [NIBR president] Mark Fishman has created a culture for us in which we get to walk the talk. We have the freedom to pursue areas in which we believe there is an unmet need and we understand the scientific basis for which that disease is active."

NIBR researchers study the molecular pathways involved in rare diseases in hopes that those pathways will lead them both to remedies for those diseases and to greater understanding of the pathways that stimulate more common diseases. For example, a drug developed by Novartis to treat an autoinflammatory ailment that affects about one person in a million has also proven effective in controlling the much more common condition of gout. The most recent success of the approach occurred last fall, when the United States Food and Drug Administration approved Afinitor, the first drug for patients with benign brain tumors associated with the rare genetic disorder tuberous sclerosis.

Changing the research culture

The road to the pathways approach began in 2002, when Novartis chairman Daniel Vasella and his board recruited Mark Fishman, a cardiologist at Boston's Massachusetts General Hospital, as head of the company's global research enterprise. Fishman quickly changed the research culture. "When he first got here, the commercial part of the organization had a strong influence on how the research part did their work-what to pursue, what diseases to study," Patel says. "One of the first things Mark and Dan Vasella did was to create NIBR as a separate organization that reports to the CEO, not to the pharma division. That act in itself really separated research from the commercial organization. Mark's insistence on highlighting that separation, rewarding scientific achievements, and pursuing unmet medical needs really did create the right culture."

Not surprisingly, Fishman's appointment met with plenty of opposition within the company. "According to those who were here, the first few years of Mark's time were controversial," says Patel, who was himself recruited in 2006 from an academic position, as chief of the division of rheumatology, allergy, and immunology at the University of North Carolina. …