But an even more significant contributor to costs is R&D. Every drug maker faces high R&D costs, but Genzyme's per-patient spending puts the company in another class. Rare-disease trials, says Meeker, "are more complicated because you have so few patients, so you need to get the maximum amount of information from those few. You can compensate for that if you have thousands of patients, because the numbers do the work for you." Trials for enzyme replacement treatments require biweekly, on-site infusions that take several hours. To get the drugs approved, complex measures, such a heart, kidney, and skin biopsies, must be taken.

Myozyme Take the company's leading pipeline candidate, Myozyme. The drug is an enzyme replacement therapy for Pompe disease, a currently untreatable condition that causes weakened muscles and difficult breathing. Pompe affects adults, but it is most common—and devastating—in children.

"These are kids who, when they should be sitting, they cannot sit," says Georges Gemayel, executive vice president of therapeutics, renal, and transplant at Genzyme. "They are just slumped; they fall on themselves. These are kids who, very quickly, stop being able to breathe on their own."

Genzyme covered travel costs for children and families from Palestine and Japan who had to be flown to trial sites. Manufacturing costs also are especially high, because Myozyme is administered at such a high dose (about 20 times that of Fabrazyme).

The company is working on ways to reduce the cost of trials. One example is newborn screening, which would help identify at least new patients with diseases like Pompe. The plan is to provide reagents for newborn screening free of charge to any public institution that does the testing. By giving the reagents for free, Genzyme hopes the institutions will become part of a newborn screening program that identifies patients early on that are likely to develop a need for drugs like Myozyme. As soon as the biological need develops, treatment can be activated.

But even with improvements, there are still a limited number of patients over which to spread the cost. Total development costs for Myozyme were $500 million. So far, only 200 people, scattered throughout 14 countries, have been identified as needing the drug. That's more than $2 million per person. However it is priced (the company has made no announcement so far), Myozyme can't be cheap. Someone has to pay. The question is who—and how can they be persuaded?

Buried Treasure

Because it works with such tiny patient populations—and because its drugs are a matter of life and death for the people who take them—Genzyme has been forced to come up with its own solution to the eternal problem of pricing and access. This strategy, according to Termeer, is what's allowed Genzyme to sustain such a high price point. "The difficulty for the pharmaceutical industry has been that it developed life-saving drugs, like for HIV, and then didn't look after the access question carefully enough," he says. "We didn't fall into that trap."

On the access side of the equation, everyone who needs Cerezyme gets it, regardless of their ability to pay. Currently, 4,500 people take the drug, and about one-tenth get it at no cost. "I've never heard anyone say 'so and so family can't get [Cerezyme],'" says Sharon Terry, president of Genetic Alliance, a coalition of about 600 disease advocacy organizations. Terry says Genzyme is the "most responsible, most responsive" company she has worked with in terms of helping patients gain access to drugs.