Why Do I Have To Wait So Long?

By MICHAEL D. LEMONICK

Patience is the last thing you can reasonably ask of someone who's in the final stages of terminal cancer. For these people and their families, talk of safety and efficacy and extended double-blind trials are just so much noise. A treatment that may be available five years from now or next year or even in a few months amounts to no treatment at all. So what if angiostatin and endostatin work only in mice? If there's even a minuscule chance the compounds will cure cancer in humans too, why should the dying have to wait another minute?

Unfortunately, there are plenty of reasons. To start with, the substances are available only in tiny quantities at this point. When scientists first started making endostatin, it took 200 qt. of mouse urine to obtain less than a millionth of an ounce. Turning the compounds out in people-size doses will require entirely different manufacturing techniques. EntreMed claims it now has a way to make lots of endostatin, using yeast cells as tiny factories; angiostatin is proving a lot tougher to mass-produce.

Within a year or two, EntreMed and its partner in the project, Bristol-Myers-Squibb, will probably figure out how to make angiostatin in quantity. At that point the companies will have to apply to the FDA for permission to market them. But before the agency gives its blessing, the companies have to show that the medications work in humans, and that they don't have terrible side effects. Normally, that's a five- or six-stage process that can last 10 years or more.

Each stage takes money--to pay for the drugs, to pay the salaries of researchers and support staff--and while more money might speed things along, drug companies and universities don't always know in advance which medications will reach the market and therefore which ones to throw more money at.

Stumbling blocks lie all along the way. Sometimes the clinical trials are badly designed; a new medication may be given in the wrong dosage, or delivered to the wrong subset of patients. And even when everything's done right, chemicals that looked highly promising in laboratory animals often turn out to be dangerous or ineffective. Most experimental compounds never get out of the lab. And for every five drugs that do go into clinical testing, only one is eventually approved by the FDA.

The FDA, for its part, has tried to streamline the process. The agency recognizes that the terminally ill are a special case, and in recent years has come up with several shortcuts, including fast-track approval for some crucial medications and a "compassionate use" exemption that gives the dying access to promising but unapproved medicines.

They get access, that is, if there is enough of the drug to go around, and that's not always the case. Beth Nocera of Medford, Mass., a 41-year-old mother of two, has terminal metastatic breast cancer. Nocera wants to try Herceptin, an anticancer drug now in clinical trials. But Herceptin is expensive, and the manufacturer, Genentech, isn't making much beyond what it needs for testing. It currently gives the extra Herceptin to a limited number of women, chosen at random by a computer, and Nocera's number hasn't come up yet. "My fear," she says, "is that it's all about money and that these companies don't need us if we don't meet their criteria."

The truth is that she's got a point. But the only way to give the drug to all the women who might want it would be to take some away from the trials. While that might save some people's lives (perhaps at the expense of someone else's), it could delay still further a process that's already slow enough.

--By Michael D. Lemonick. Reported by David Bjerklie/New York

With reporting by David Bjerklie/New York