The Making of a New Disease - Pharmaceutical Executive

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The Making of a New Disease
Science is beginning to understand the role of insulin resistance. Now it's industry's turn to draw the blueprints for the biggest market yet.


Pharmaceutical Executive


Think back: When did you first hear the phrase metabolic syndrome? When did it start to become part of your business and its plans?

Maybe that second step hasn't taken place yet. But for many in pharma it's coming soon. In the past few years, scientists, researchers, and healthcare companies have been paying increasing attention to the concept that obesity, hyperlipidemia, diabetes, and hypertension-and perhaps other diseases, including some cancers-are linked.

And the pace of new developments is accelerating. For example:

  • The American College of Cardiology and the American Diabetes Association (ADA) recently launched "Make the Link," a campaign that informs physicians and consumers that type 2 diabetics run an increased risk of heart disease and stroke.
  • MSAToday.com, an alliance with a corresponding website funded by unrestricted grants from GlaxoSmith-Kline (GSK), offers physicians information about metabolic syndrome and continuing medical education credit.
  • November 2003 saw the launch of the first annual scientific meeting devoted to insulin resistance, which most scientists believe is the cause of metabolic syndrome.
  • In early 2004, a new society devoted to metabolic syndrome called the International Society of Diabetes and Vascular Research is expected to launch and begin publishing its own journal.


Blueprint for a disease
It's not just that metabolic syndrome has become better understood, better publicized, or better supported by an infrastructure of journal articles, meetings, and associations. Behind those events and dozens more like them something far more basic is happening: A new disease is being born.

Unlike a new pathogen bursting from the jungle like Ebola or mutating from something familiar like each year's "new" strain of influenza, metabolic syndrome must be both socially and scientifically constructed. Well-known medical facts have been reorganized into a new understanding. And with that knowledge comes the need and opportunity for new research, new modalities of treatment, and, on the pharma side, new market risks, demands, and opportunities.

"Just think of cholesterol," says John Wendel, PhD, a medical anthropologist at Integrated Marketing Associates. "Cholesterol wasn't something people talked about 20 years ago. Merck spent years getting physicians to think about it as a big problem. Now they do."

The emergence of cholesterol reduction as a market was a major event for pharma. Metabolic syndrome promises to be as big or bigger. Like any new disease, this one offers significant challenges to pharma. But for companies that meet them-especially the challenge of finding an appropriate role for medication in treating a disease with a large lifestyle component-metabolic syndrome will be a force reshaping products, companies, and markets for decades to come.


"Nothing helped metabolic syndrome more than the establishment of the ICD9 code." - Yehuda Handelsman, MD
Discovering Syndrome X The observation that obesity, hyperlipidemia, diabetes, and hypertension frequently can be found together dates back to the late 1970s, when German researchers named the phenomenon "metabolic syndrome." (See "What's in a Name?" page 52.) But no one paid much attention until 1988, when Gerald Reaven, MD, a professor of medicine at Stanford University, articulated the risk factors related to what he called "Syndrome X" during an acceptance speech for the ADA's Banting award. Reaven was also the first to focus on insulin resistance as the underlying cause of metabolic syndrome.

Insulin resistance is the state in which a person's normal level of pancreatic insulin secretion is inadequate to unlock glucose from food and transport it to the body's cells for energy. The condition is thought to be genetic, but it can be aggravated by obesity and physical inactivity because fat cells aren't receptive to insulin. Most patients with type 2 diabetes, though not all, are insulin resistant and take medications to sensitize the body to insulin, address insulin deficiency, or target other problems related to blood-glucose control. But insulin resistance doesn't always lead to type 2 diabetes. Reaven says that most people with insulin resistance don't even develop the disease.

In 1989, Norman Kaplan, MD, professor of internal medicine at the University of Texas' Southwestern Medical Center identified four risk factors for heart disease-upper body obesity, impaired glucose intolerance, high triglyceride levels, and hypertension-and dubbed it the "Deadly Quartet."

Underlying the Quartet: the excessive blood-insulin levels often associated with insulin resistance.

Additional studies in the early 1990s-most notably one by a team led by Ele Ferrannini, MD, who heads the European group for the research of obesity, hypertension, and insulin resistance based in Pisa, Italy-confirmed the basic insights of the preceding years. But it took a decade before a fairly rapid series of developments took metabolic syndrome out of the academic realm and introduced it into the world of medical practice.


Timeline
First, in 1999, the World Health Organization issued its own description of metabolic syndrome. Yehuda Handelsman, MD, co-chair of the International Committee for Insulin Resistance and medical director of the Metabolic Institute of America, explains, "They again described that same constellation of abdominal obesity, elevated fasting blood triglycerides, low levels of HDL or 'good' cholesterol, high fasting blood sugar, and high blood pressure, and said if somebody has those, they have a high risk of developing diabetes and cardiovascular disease (CVD)."

Two years later, the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III released a simplified set of diagnostic guidelines. (See "ATP III Criteria," page 51)

"NCEP came out with their guidelines in the JAMA of May 2001," says Christine Beebe, director of education and scientific affairs for Takeda. "That was a call to action for physicians to not only focus on LDL cholesterol, but on metabolic syndrome and this constellation of other risk factors to prevent CVD." More important, metabolic syndrome received its own code in the International Classification of Diseases, Ninth Revision (ICD9). In a world in which a condition isn't really a disease until it becomes part of physicians' paperwork, metabolic syndrome had crossed an important threshold.

"The fact that metabolic syndrome has been identified as an actual disease state is a huge step in the right direction," says Beebe. "Before that, physicians didn't have a reason to focus on these individuals before they developed diabetes or CVD."


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