Cheaper Treatment for Disease Backed

Patients with Gaucher disease, who now are dependent upon one of the world’s most expensive medications, can cut treatment costs by 75% simply by reducing dosages and increasing frequency of treatment, according to researchers at the Scripps Research Institute.

The finding published in today’s issue of the New England Journal of Medicine is good news for the estimated 7,000 Americans with severe cases of Gaucher disease, a hereditary condition that causes a potentially deadly increase in the size of the spleen, liver and bones.

One year’s treatment with Ceredase, a drug that has been on the market for little more than a year, can cost more than $300,000. The drug is so expensive because a key element must be painstakingly extracted in minute amounts from human placentas.

Scripps researchers report that Ceredase is every bit as effective--but far less costly--when administered in smaller doses and at more frequent intervals. Treatment costs generally can be reduced by as much as 75% without reducing the drug’s effectiveness, said Scripps molecular biologist Ernest Beutler.

However, researchers elsewhere in the country have questioned whether results of Beutler’s continuing study, which is based on a relatively small group of Gaucher patients, can be safely extrapolated to the larger community.

In the U.S., Gaucher disease is most common among descendants of Eastern European Jews, but also appears in the non-Jewish population. Until 1991, when the U.S. Food & Drug Administration approved Ceredase for use, severe cases of Gaucher disease were treated largely with surgery to remove swollen organs or through bone marrow transplants.

Beutler focused his research on the “most economical way to effectively use” Ceredase, which is marketed worldwide by Boston-based Genzyme, the drug’s sole manufacturer.

The compounds used to create Ceredase were discovered and tested at the National Institutes of Health.

Genzyme undertook the expensive process of developing and manufacturing Ceredase under the federal Orphan Drug Act, which gives drug companies financial incentives and exclusive marketing rights in return for the high-risk task of developing drugs targeted at small numbers of patients.

Ceredase replaces a missing enzyme in patients’ bodies, allowing organs to function properly by expelling fats that otherwise accumulate in Gaucher patients at potentially crippling levels.

Beutler, who has studied potential enzyme treatments for Gaucher disease since the late 1960s, began experimenting with different dosages of Ceredase because the manufacturer “had no incentive” to determine if lower doses would be effective. “We wanted to know how best to use this drug,” Beutler said. “And we found out there was a lot more bang for the buck with lower doses and the frequent (administration) schedule.”

Genzyme Senior Vice President Alison Taunton Rigby on Wednesday said that most physicians who administer the drug believe that the drug is effective when administered in larger amounts at two-week intervals, as is recommended by most scientific studies.

But doctors also believe that, after initial high-dosage treatments, dosage can be dramatically cut back as soon as six months after treatment begins, Rigby said. Most physicians now “start with the higher doses, and after six months, cut down dosages,” Taunton Rigby said.

Only about 6% of physicians are using Beutler’s low-dose, high-frequency regime “even though they’ve known about it for a while,” Rigby said.

Rigby also said that most scientists question whether “you can extrapolate the (La Jolla) results to all Gaucher patients because they vary greatly by individual . . . Some have platelet problems, some have anemia . . . you have to look at each patient individually.”

But Beutler on Wednesday argued that the Scripps findings have been replicated by researchers in Israel and Holland, are solid evidence that the low-dosage, high-frequency regime works because Scripps’ patients “were, if anything, more sick than the ones” included in previous studies that led to the high-dosage, low-frequency regimen.

Scripps’ findings are “good news” for Gaucher patients, Beutler said. “The only bad news is for Genzyme, whose representatives have continue to promote a more expensive treatment (regimen). “ “

Rigby also questioned whether Beutler’s low-dose, high-frequency program saves patients money because the drug can only be administered through infusion, a lengthy and potentially expensive process. The low-frequency regime requires just 26 infusions annually, contrasted with 144 under Beutler’s program.

Genzyme officials argue that the added costs of administering Ceredase as proposed by Beutler could increase costs by at least $25,000 annually. They also question whether patients would be able to maintain that kind of treatment “when they’re trying to lead normal lives,” Genzyme spokeswoman Kathleen Riley said.

But Beutler maintained that advances in infusion technology have made it possible for patients to do their own infusions at home, at considerably less cost. Patients involved in the studies in La Jolla, Israel and Holland completed 9,000 infusions, mostly at home, without incident, Beutler said.