In the fourth grade, Angelo Tufano was so short he looked like a kindergartner, and he was miserable. "I was picked on a lot. Other kids called me 'midget' and 'shrimp,"' says Angelo, now an 18-year-old student at Columbia College in Chicago. "I used to cry." His mother, Carmela, persuaded an endocrinologist to prescribe a growth hormone, even though tests showed he didn't qualify for a prescription. Eventually she talked her insurance company into dropping the monthly co-pay for the drug from $700 a month to $5. Now Angelo stands at 5-foot-9 -- a full 10 inches taller than his doctors predicted he'd be without the drug. "I was worried society wouldn't accept him," Carmela says. "As a parent, you do what you have to do."
Parents such as Tufano are suddenly facing a plethora of ways to stack inches onto their height-challenged children. In June, Genentech Inc. (DNA ) quietly won approval from the U.S. Food & Drug Administration to expand the market for its growth hormone, Nutropin, which was approved in the early 1990s to treat children whose bodies don't produce adequate amounts. Now Genentech can also market Nutropin to children, like Angelo, with idiopathic short stature (ISS), meaning they're short for no obvious medical reason. And on Dec. 12, the FDA could approve iPlex from Insmed Inc. (INSM ) in Glen Allen, Va. -- the second entry this year in an entirely new class of drugs to treat children whose bodies produce growth hormone but can't benefit from it.
As with earlier treatments for short stature, the latest wave of drugs has met with a chorus of controversy. The companies argue that their products offer a safe way for parents to insure their children against a lifetime of discrimination in work and romance. Critics respond that drugmakers are profiting off a condition that's merely cosmetic. "Society is buying into the idea that someone who's short has a medical problem," says Nancy Worcester, a professor of women's studies at the University of Wisconsin-Madison. In 2003, while serving on an FDA advisory panel, Worcester voted against approving Eli Lilly & Co.'s (LLY ) growth hormone, Humatrope, for ISS. Lilly eventually won. "I'm real worried about the medicalization of shortness," Worcester says.
The concerns are not all sociological. Growth hormones, on rare occasions, can cause dangerous side effects, such as pressure on the brain. Some patients have developed leukemia, though the link to growth drugs is uncertain. Experts are also troubled by the wide variance in effectiveness: Some children gain only a few inches, while others shoot up.
The debate gets even more heated when economists enter the fray. Studies have long indicated that short adults earn less money than their tall co-workers. New research expands on that finding, showing that even short teenagers who grow into normal-size adults are doomed to earn up to 13% less in the workplace than people who were tall as teens. Daniel Silverman, an assistant economics professor at the University of Michigan who headed the latest study, based it on data from ongoing surveys of more than 17,000 people in Britain and 12,000 in the U.S. Silverman plans to publish additional studies next year. Initial indications show that the earnings gap widens over the short teen's life -- again, regardless of how tall an adult he or she becomes. This "height premium," he adds, is comparable to wage gaps caused by race and gender.
Silverman says the earnings disparity isn't classical discrimination -- it's not about employers secretly agreeing with the old Randy Newman lyric, "short people got no reason to live." Rather it's because short kids don't participate as much in sports, clubs, and other social outlets, so they have less opportunity to learn social adaptability, team building, and other interpersonal skills. Therefore, he concludes, the possible return on a $25,000-per-year investment in growth hormone -- as much as a 2.7% boost in wages for every inch gained -- is too tempting to ignore. "If you're worried about a kid's future wages and you want to use a drug, I can't say that's a bad thing to do," Silverman says.
The shortness stigma certainly helps the drug companies. Prior to 2003, when the FDA approved Lilly's drug Humatrope for ISS, sales of that product grew in fits and starts, since it was marketed to children and adults with rare disorders that impeded their growth. Once children could take it without proof of an underlying disease, the climate changed. In 2006, sales should come in at $460 million -- 40% higher than they were in 2002 -- estimates Stephen M. Scala, an analyst for SG Cowen Securities in Boston. Last year, U.S. growth hormone sales overall jumped 16%, to $711 million, and they're up 10% in the first nine months of this year, compared with the same period in 2004, according to IMS Health Inc. (RX ).
That's a lot of momentum, considering the harsh restrictions the FDA places on drugmakers in this category. Genentech understands those restrictions all too well. In 1999, the company pleaded guilty to federal criminal charges that it improperly promoted its growth hormone. The company paid a $50 million fine. In 2003, the FDA clarified that doctors should prescribe a growth hormone for ISS only when a child is 2.25 standard deviations below the mean height for age and sex -- which translates to roughly the shortest 1.5% of children. And drugmakers must adhere to strict marketing plans. "We can't do any direct-to-consumer advertising, and we monitor the market for inappropriate use," says Dr. Matt Rhoa, director of specialty biotherapeutics for Genentech. The target market, he says, "isn't the kid who's shorter than his classmates. These are very, very short kids."
Despite vigilance on the part of drug marketers, some parents will still be tempted to use growth hormone to try to get Johnny on his high school basketball team. While hard numbers on off-label use are scarce, many physicians fear that growth hormone could be turning into a lifestyle drug demanded by kids, or their parents. Nelly Mauras, chief of the division of endocrinology at Nemours Children's Clinic in Jacksonville, Fla., says one father berated her after she refused to prescribe a growth hormone for his son, who she predicted would grow to 5'9" without it. The father "became absolutely irate," Mauras says, and the child was equally adamant he deserved the drug. "He started talking like he was going to be a dwarf." What's likely to happen when Dad goes for a second or third opinion? "No doubt he'll get someone to prescribe it," Mauras says.
Even on-label uses of growth hormones can raise troubling questions. For example, if physicians continue to give them to children who fall below the mean, could the mean rise, too, creating a whole new class of kids who qualify for the drug? The world is already getting taller: In the last 40 years, the mean height of American boys ages 6 to 11 has jumped nearly an inch. While some of the gain may have come from improved nutrition, adding drugs to the mix could fuel the frenzy and draw more children into it. Even if everyone grows, relatively, "There will always be a short cohort," says Ross Feldberg, associate professor of biology at Tufts University. "It's scary."
Growth hormones are likely to remain in the spotlight for another reason: They could become the first-ever biotech drugs to become available in generic form. Novartis (NVS ) has been petitioning the FDA to approve its generic-type growth hormone since 2003. Unable to pry loose a response, the company sued the agency in September to force a ruling. Once a cheap alternative becomes available, demand -- legitimate and otherwise -- could skyrocket.
Soon parents with short children will probably start hearing about a new class of drugs. In August, biotech company Tercica Inc. (TRCA ) won FDA approval for Increlex, a protein that could help about 6,000 children a year who don't grow properly. These patients are deficient in a protein, called IGF-1, which is another vital part of the growth process. Rival Insmed could have its form of IGF-1 approved in December, though it has to clear additional regulatory hurdles to market the drug in the U.S. For Carrie Reeb, a 17-year-old who participated in a Tercica trial, IGF-1 has made a world of difference. "I would have been only three feet -- about counter height," says Reeb, who lives in Charlotte, N.C., and is now just under five feet. "I'm small, but I'm normal."
Normal, of course, will always be a matter of debate among children, parents, and physicians. And the controversy will grow -- side by side with revenues -- as new drugs hit the market.
By Arlene Weintraub, with Michael Arndt in Chicago