Inspiration comes from the most unexpected places. An international team of scientists discovered a mathematical law that can be used to predict the spread of an infectious disease across the country. The key to their discovery? Wheresgeorge.com, a recreational Web site that allows people to track dollar bills by serial number.

    One of the researchers, Lars Hufnagel, a post-doctoral fellow at the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara, said the team was looking for a way to understand how diseases spread geographically inside a country. Airline travel routes can be used to predict international infection patterns, he explained, but domestic travel takes too many forms to successfully use any one as an indicator.

    They were looking for something quantifiable that traveled the way diseases travel but was not specific to any illness, he said. The wheresgeorge data were such a good match because currency, like disease, is almost always attached to humans when it travels. 

    Human travel has no scale, Hufnagel said, because people frequently travel short distances, sometimes travel moderate distances, and occasionally travel long distances. But the team found that human travel in the United States could be described by a mathematical formula known as a scaling law. 

    Scaling laws, which look a little like logarithmic functions to the unsophisticated, are used to determine proportionality. The laws give a sense of perspective to observers, allowing them to understand variables. A simple example of scaling: Geologists often put a hammer next to a rock when they photograph it for their records. By using a hammer of constant size, the scientists can use a formula to compare the size of rocks in two different photographs. 

    It turns out that a simple scaling law can describe the way humans travel and predict how a disease spreads.

    “The scaling law is always the same -- from a few miles up to across the country,” Hufnagel said about the formula that describes human travel. “It doesn’t depend on where in the United States you are.”

    The next step, according to Hufnagel, is to couple this information about how disease spreads geographically with local infection data that demonstrate how infections spread from person to person. Such data show how many people one sick person infects.

    Together these data can be used to create a model, which the team plans to test by simulating past disease epidemics and comparing their predictions to the actual event.

    Although the statistical laws discovered by the wheresgeorge study are specific to the United States, Hufnagel believes the findings will translate to other developed nations with sophisticated transportation systems.

“I would be very surprised if it is different,” he said

Articles

An entertaining Internet program that allows Americans to see where a dollar goes after they spend it, helped scientists develop a formula for how infectious diseases spread geographically in United States.

Popular Web Site Used to Predict Epidemic Patterns

In an attempt to increase shareholder value, ImClone Systems Inc has opened itself up to a potential sale or merger. Best known to the public for its shares’ role in the Martha Stewart insider-trading scandal, the embattled company retained investment bank Lazard Ltd to explore its options. But industry observers are skeptical that ImClone will find a buyer at its current $3 billion valuation.

    “The decision to sell is definitely out of weakness,” said Peter Young, president of specialized investment-banking firm Young & Partners.

    The company has only one marketed product, colorectal cancer drug Erbitux (cetuximab), which will face new competition if Amgen and Abgenix’s panitumumab is approved as expected. The new drug would have a dosing advantage over Erbitux, because it is taken biweekly rather than every week.   

    ImClone’s desire to sell just as panitumumab emerges from the pipeline suggests that the company fears Amgen, and also that it is devaluing Erbitux, said Walter Birch, director of Michael Kelly Associates, a managerial recruiting company that specializes in healthcare and financial services.

    In addition, a marketing agreement for Erbitux gives Bristol-Myers Squibb 61 percent of sales. The company also owns 17 percent of ImClone stock. Merck KGaA owns the rights to market Erbitux outside of the United States.

Because so much of ImClone’s value is tied up in this agreement to market its only product, the company does not have much to offer a potential buyer, according to Young.

    “No one is going to buy it for Erbitux,” Young said.

    As a result, Young believes, ImClone will have to convince potential buyers of the strength of its pipeline, a feat many consider difficult.

    “There’s nothing in the pipeline worth $3 billion,” Birch said.

    One possibility is to stress the likely approval of Erbitux for other indications, said Ben Bonifant, head of the Business Development practice at Campbell Alliance, a biotech and pharma management-consulting firm. It is expected to gain approval for head and neck cancer this year.

    Morningstar analyst Karen Andersen believes expanding Erbitux’s label will keep sales strong. 

    Another selling point could be ImClone’s research capability, according to Birch. Likewise, Andersen emphasized that a recently constructed manufacturing plant could also hold value for potential buyers.

    “Biologic manufacturing capacity could be highly valuable to the right partner, and the additional support should help ImClone ride out and possibly shorten the awkward stretch between panitumumab’s launch and it’s next drug approval,” she wrote in a Jan. 26 report. 

    But Bonifant said the field of potential buyers is probably limited to companies that already have relationships with ImClone.

    Many believe BMS is the obvious buyer in this situation. In a recent report, WR Hambrecht analyst Patrick Flanigan guessed that the company already declined to purchase ImClone.

    Young agreed that this was a strong possibility. He also speculated that BMS might still be interested but wants ImClone’s value to be decided by the market, rather than negotiations. 

    Birch said this was possible, but would probably indicate that two companies had been unsuccessfully negotiating for a long time.

    Although many of the problems ImClone faces are unique to its situation, others are common to specialty pharma and biotech companies. Flanigan compared ImClone’s situation to Serono and Sepracor, which have not been able to find buyers for almost a year.

    Richard Vanderveer, chief executive officer of market research firm GfK V2 said mergers and acquisitions are too frequently used in an attempt to revive problem-ridden companies. But this solution only creates more problems in the long run.

    “I think it’s time to return to a time when companies prided themselves on growing within their own culture,” Vanderveer said.

Upcoming competition, a weak pipeline, and existing marketing agreements limit the pool of prospective buyers, experts say.

ImClone Searches for Potential Buyer

Bristol-Myers Squibb set aside $185 million on Jan. 23 to fund the settlement of a class-action lawsuit brought by shareholders who claim the company misled them about Vanlev (omapatrilat), a cardiovascular drug. The lead plaintiff, the LongView Collective Investment Fund of Amalgamated Bank, charges that the company’s public statements hyped Vanlev’s blockbuster potential, driving up BMS stock, even thought the drug was having problems in clinical trials. The drug was never marketed to the public.

    The current settlement offer would require BMS to post clinical trial results online for every drug it plans to market anywhere in the world. According to the plaintiffs, this requirement is a significant step towards the reforms spelled out in the Fair Access to Clinical Trials Act of 2005. 

    “The drug discovery protocol negotiated with Bristol-Myers Squibb as part of the settlement of this class action goes further than what Attorney General Spitzer obtained for the Glaxo settlement,” said Thomas Dubbs, partner at Labaton Sucharow LLP and lead counsel for the Amalgamated Bank. 

    But Joseph Leghorn, a partner at Nixon Peabody LLP, sees no major breakthrough. The settlement is not a great leap beyond the reforms New York Attorney General Eliot Spitzer obtained from GlaxoSmithKline in connection with Paxil disclosures, Leghorn said. He believes this new degree of transparency is part of a continuing trend.

    “I don’t think this is much different than what has been going on in the industry anyway,” he said.

    In general, the pharmaceutical industry is making clinical trial results more transparent. The main issue is not whether to disclose data from trials, but when, said Thomas Hartman, a partner at Foley and Lardner LLP.

    Because it can take weeks or months for a company to fully understand trial data, it is difficult to say when they should make this information available, Hartman indicated. 

    This is especially true in the earlier stages, when the company is using results to refine a potential drug’s target population, according to Leghorn.

    Elizabeth Nowicki, a law professor at University of Richmond, believes it is better to say too much too soon than too little too late, although she acknowledged that early disclosures “can hit the bottom line hard,” 

    Deciding when to release trial data is complicated, she said. It is important to balance the level of uncertainty in the results against the seriousness of any potential negative side effects. 

    Hartman added that releasing trial information too frequently could confuse investors, because the interpretation of results can change as the company further analyzes the data.

    One possible solution, Nowicki said, would be to summarize clinical trial results in plain language, so that investors can understand the scientific process of drug discovery.

    Hartman added that if a company releases positive trial information about a drug candidate, it is crucial that the company also makes negative results public quickly. If a company has remained fairly quiet about the upside of a pipeline drug, then it will probably draw less scrutiny for being slow to release negative results.

    Companies should also be very judicious about what executives say publicly regarding drugs in the pipeline, Leghorn added.

    Dubbs hopes the settlement will “jumpstart” the Fair Access to Clinical Trials Act. This could resolve many of the uncertainties surrounding transparency.

    “I don’t think that you’re going to see much more legislation,” he said. “But there might be some rulemaking.”

The class action settlement illustrates a trend toward increased transparency, lawyers say. But issues about timing clinical trial disclosures are still unresolved.

Pharmaceutical Executive-01-31-2006

Popular Web Site Used to Predict Epidemic Patterns

ImClone Searches for Potential Buyer

BMS Reserves $185 Million for Vanlev Suit