Almost 40 years ago, pediatrician Harry Shirkey called children’s drugs the “therapeutic orphan” of the industry, and unfortunately that still holds true, says Stephen Spielberg, a pediatrician and 30-year veteran of the pediatric drug-development industry. As a rule of thumb, 80 percent of medications for children are not adequately tested.

Why? Even after Clinton-era legislation to encourage more testing of drugs in pediatric patients, there is still a shortage of research. The trials are difficult to run, with poor returns on investment for industry. Outside of antibiotics and asthma meds, which are a large part of the kids’ market, the dosing of pediatric drugs remains mostly a guessing game.

IPI Launched

That’s why the Boston-area non-profit Institute for Pediatric Innovation was launched in 2006. And that’s why Spielberg just signed on to head up the institute’s five-year pediatric pharmaceutical reformulation program: to get to work doing the research that industry hasn’t gotten around to.

To illustrate why the effort is important, Spielberg points to tuberculosis.  “To treat it, you need to give multiple different medications for months,” he explains. “And for adults, there are tablets that contain three different drugs. They take one tablet. But there is no such combination for kids.”

IPI’s Spielberg

Ad Hoc Rx

Instead, parents are faced with “ad hoc-ing it,” says Spielberg—crushing up adult doses, dividing them according to the pediatrician’s best guess, mixing them in a viscous, attractive food like apple sauce, and hoping the child eats it. Not terribly scientific.

Even if the child does comply, the dose may not be safe. It may be too much. Or too little, which in a condition like tuberculosis can lead to dangerous resistant organisms that are harder to treat.

“Those are the kinds of frustrations we’ve faced and now have an opportunity to address,” says Spielberg, who stepped down as dean of Dartmouth Medical School to join the institute. Before that, he was VP for pediatric drug development at Johnson & Johnson.

Wish List

The program’s first order of business, he says, is to get a “wish list” from children’s hospitals and other entities that work closely with kids. He wants to find out which currently marketed drugs are in the most need of being reformulated for the 0-to-18 set.

Next, Spielberg said, the organization will choose a few of those per year and ask various schools of pharmacy to work on reformulating them to suit the metabolic differences in kids of various ages. They’ll also focus on new delivery mechanisms; small kids can’t take tablets.

After that, says Spielberg, the organization will work to find a manufacturer for each new formulation who will run the necessary trials and eventually manufacture and distribute the drug. Initially, says Spielberg, he expects the trials to be small and inexpensive, with the research aspects of the reformulation limited simply to demonstration of bioequivalence.

If everything goes as planned, all of this will be paid for through public-private partnerships that the institute is in the midst of arranging.

Funding Partners

Already on board as partners are Children’s Mercy Hospitals and Clinics, which funded the organization’s start-up, as well University Hospitals Rainbow Babies and Children’s Hospital and the Lucile Packard Children’s Hospital at Stanford. Other contributors include the Ewing Marion Kauffman Foundation, Children’s Medical Ventures, AGA Medical and Oxford Bioscience Partners.

Last year the institute raised $1 million. The five-year goal? $10 million.

Parallel Efforts

Other efforts to do much the same thing are under way as well. The Best Pharmaceuticals for Children Act, which came about in 2002, has helped some, says Spielberg, but has still left gaps. And more recently (in December), the World Health Organization launched its ‘Make Medicines Child Size’ campaign.

Another thrust of Spielberg’s program, he says, will be to use developing technology to enhance stability of various children’s drugs.

Taking the Heat

“The vast majority of children in the world live in places without refrigerators, and if you’re going to get a medicine out to them, you need to work on heat-stability issues,” he says. “Even when there is a refrigerator, maybe the family is going on a trip, or the child is in childcare (where there is no refrigerator). So there’s a need for new technology there. We hope to have a huge impact on shelf life.”

The institute is working fast. By the end of the year, says Spielberg, he hopes to have two research groups digging in deeply on two “wish-list” compounds, with a partner waiting in the wings to take over manufacturing.

—by Suz Redfearn