Cardiology and anaemia lose out in the hunt for the next pharmaceutical blockbusters.
When Wyeth Pharmaceuticals announced last week that it would cut some of its research and development (R&D) programmes in women's health, the decision seemed counterintuitive. The pharmaceutical giant, based in New Jersey, is known for its strong work in contraceptives and hormone-replacement therapy. The decision also sounded familiar: on 30 September, the New York-based company Pfizer said it would pare down its R&D efforts as well, eliminating research programmes in nine disease areas including cholesterol — an area in which Pfizer has been a leader.
Both companies, like much of the pharmaceutical industry worldwide, are tightening their belts as they face looming competition from generic drugs, increasingly conservative drug regulators and diminishing product pipelines. Pfizer faces patent expiration in 2010 on its multibillion-dollar cholesterol-lowering drug, Lipitor (atorvastatin), and Wyeth has launched a cost-cutting effort called Project Impact that aims to trim thousands of employees from its payroll.
In response to such challenges, the drug industry is shifting research away from its bread-and-butter 'primary care' products — those likely to be prescribed by a primary-care physician, once prized for their massive markets — to 'speciality' drugs prescribed by specialists in fields such as oncology and neurology. These drugs captured 45% of pharmaceutical sales in 2006, up from 39% in 2001 (M. Gudiksen, E. Fleming, L. Furstenthal and P. Ma, Nature Rev. Drug Discov. 7, 563–567; 2008). "Big pharma has prided itself on being very diverse in its approach to R&D," says Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development in Boston, Massachusetts. "But that's just not feasible these days in the current market conditions." (see 'Drug industry rides the stock market')
“New drugs must perform much better than those already on the market before regulators are willing to take a chance. ”
Wyeth plans to shrink the number of diseases it tackles from 55 to 27. It will instead increase its focus on cancer as well as inflammatory, metabolic and neurological disorders — fields that remain on Pfizer's R&D slate as well. "These areas represent our highest probability for success," says Pfizer spokeswoman Kristin Neese, who cites unmet medical need and potential for market growth as two selection criteria. Meanwhile, Pfizer's eliminated research programmes read like a grocery list of primary-care conditions: cholesterol, osteoporosis, gastrointestinal conditions, osteoarthritis and anaemia.
Pfizer's decision to eliminate cholesterol research comes as Lipitor, one of a class of cholesterol- reducing drugs known as statins, brought in US$12.7 billion last year as the world's best-selling drug. Still, "the cholesterol market is totally saturated," says Jason Bowers, an analyst for the market-research firm Decision Resources in Waltham, Massachusetts. "And as soon as Lipitor goes off patent, the statin market is going to fall."
Industry in general is pulling away from research on cardiovascular disease, even though it remains the leading cause of death in the United States. A recent analysis of clinical trials from 2005 to 2007 revealed a decline in the number of drug trials against leading cardiovascular conditions such as high blood pressure and high cholesterol (J. P. E. Karlberg, Nature Rev. Drug Discov. 7, 639–640; 2008).
That's not totally surprising, says Damien Conover, an analyst for Morningstar, an investment-research company based in Chicago, Illinois. Recent scandals about the dangerous side effects of drugs, such as the increased risk for heart attack and stroke in those taking Merck's painkiller Vioxx, have made the US Food and Drug Administration more cautious about drug approvals. Drugs that have been on the market for years are more familiar and often viewed as less risky, meaning that new drugs must perform much better than those already on the market before regulators are willing to take a chance on approval. Meanwhile, health-care insurance plans also view new medications with increased scrutiny. In crowded fields such as cardiovascular disease and other primary-care areas, the hurdle is simply too high for companies to risk it.
This makes specialized fields such as immunology and neurology attractive alternatives. The number of cases of rheumatoid arthritis, for example, has increased faster than expected, generating a large population of patients that companies are now scrambling to target.
And some predict that the next blockbuster drug will be a treatment for Alzheimer's: a disease with a growing market, a tremendous unmet need for treatments, and a cadre of patients and family members willing to pay high prices for therapy. Wyeth has been a leader in Alzheimer's research, both in therapeutics and in development of a candidate vaccine. "People think that in the next five or eight years, there's likely to be a major advance, and if you're the first company with that advance, the payout will be gigantic," says Erik Gordon, associate dean of technology management at the Stevens Institute of Technology in New Jersey.
Meanwhile, research investment in oncology has been growing steadily across the industry. Some view Indiana-based Eli Lilly's recent $6.5-billion bid for the biotechnology firm ImClone as a sign of increased demand for cancer drug candidates. Health-care insurance plans, too, have traditionally been more willing to pay high premiums for cancer therapies — although there are signs that this attitude may be changing. And the pharmaceutical industry has recently embraced the drive towards genetically targeted, individual treatments in oncology — a concept that once made companies cringe because it reduced the market for a given drug.
That, says Conover, was before the industry realized that patients would pay tens of thousands of dollars for an expensive new drug. "All of a sudden," he says, "'market limiting' is OK."