No Child Left Behind

Childhood cancer garners sympathy from all, but drug development from few.

The drug’s manufacturer, Genzyme Corporation, has long taken interest in uncommon diseases, and children’s cancer seemed like a natural extension of company philosophy, says Michael Vasconcelles, MD, Genzyme’s vice president of clinical research. Clolar had been tested and carried to the regulatory finish line by the small San Antonio-based firm Ilex Corporation. Genzyme acquired Ilex, along with the drug, just before approval. (Clolar is now in the final stage of testing for leukemia in adults.)

“For Genzyme, this was a usual and customary program to inherit,” Dr. Vasconcelles says. “We’re used to identifying unmet needs.”

For drug companies that do not have a business strategy built on rare diseases, lawmakers are using persuasion in the way only the government can. The federal Food and Drug Administration first tried in 1998 to require pediatric testing of drugs. The rule was invalidated in 2002 on the grounds that the FDA had overstepped its authority, leading Congress to pass the Pediatric Research Equity Act in 2003. In late 2007, Congress reauthorized the law along with another measure called the Best Pharmaceuticals for Children Act, which rewards drug companies who seek pediatric labeling with a six-month extension of exclusive marketing.

But opinions vary on the degree to which these laws have helped children. In May 2007, the Government Accountability Office reported that between 2002 and 2005, the FDA asked drug companies to study 214 patented drugs for pediatric use. In 173 cases—including 28 cancer drugs—the manufacturers agreed. Some findings have given doctors pause. GAO’s Marcia Crosse told Congress that “pediatric drug studies conducted under BPCA have shown that the way that some drugs were being administered to children potentially exposed them to an ineffective therapy, ineffective dosing, overdosing, or previously unknown side effects—including some that affect growth and development.” None of the 41 remaining drugs have been tested, even though the FDA asked for some to be examined by the National Institutes of Health. In addition, the GAO reported, “few of the off-patent drugs identified by NIH as in need of study for pediatric use had been studied.”

An analysis published in 2007 in Nature Reviews Drug Discovery, from Asher Schachter, MD, of Children’s Hospital Boston, found that the government rule change in 1998—the early attempt to require pediatric studies—appeared to accelerate the time for pediatric approval from seven years to around four years. However, the flow of new pediatric drugs submitted for approval overall did not significantly increase.

In general, companies have little incentive to study their drugs in children, Dr. Schachter says. With few officially approved alternatives, physicians will use the drugs regardless, prescribing them off label. However, because the drugs are officially considered unapproved in pediatrics, companies “are not culpable because they say on their label ‘not for use in children.’ ”

“Delaying the performance of pediatric clinical trials until a drug’s patent is approaching expiration places the risks of off-label prescribing entirely on children,” Dr. Schachter wrote in the journal.

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