Before he was even a year old, Luis Fernando Rojo was near death, suffering from a fatal disease that was causing his organs to fail and blisters to break out all over his small body.
Commercialized therapies weren't helping the Florida infant, and his doctors at Holtz Children's Hospital in Miami were desperate. So they called Baltimore's Osiris Therapeutics and asked a costly favor: They wanted free access to one of the company's experimental, unapproved and expensive stem cell treatments, allowable under a provision within federal regulations. Osiris said OK.
"After he was given the drug, he improved 100 percent," the boy's father, Hilario Rojo, said last week through a Spanish-speaking interpreter. Today, the toddler is 28 months old and faring well.
Biotechnology companies often deal with deadly diseases, developing drugs for the world's sickest patients, many of whom have few treatment options and often are willing to try anything to see if it will help save them. But relatively few eligible businesses want to make developing drugs available in circumstances like Luis', in part because such efforts do little to move the product to the mass market.
The U.S. Food and Drug Administration allows people to try therapies that haven't been approved for marketing on a "compassionate use" basis, as long as certain criteria are met. But the agency, which is considering changes to its regulations meant to expand access to such drugs, can't compel companies to offer up their investigational products.
And many say there are few reasons a business would want to make the offer, given the financial pressures they're already facing in drug development. Others worry that these experimental drugs can offer false hope to patients and could be dangerous given the lack of information known about how, or if, they work.
Such treatments offer little in the way of useful data, can be detrimental to clinical trials and often cost thousands of dollars to provide. Insurance companies typically won't reimburse patients for such therapies. And those who need them often can't afford them, leading sympathetic companies to forgo charging.
"I can't see any consistent benefits or any good business reasons why you might want to do this," said Christopher-Paul Milne, assistant director for the Tufts Center for the Study of Drug Development. "It's probably just for the sake of compassion."
The country has a long history of allowing access to unapproved drugs in serious or life-threatening situations, with more than 100,000 people being treated this way over the years, according to the FDA. Between 1997 and 2005, the agency said it received an average of about 660 requests for individual emergency treatments each year.
But it wasn't until 1987 that the FDA outlined rules for such drug dispensation, requiring that the therapies be: designed to treat grave illnesses, have no like alternatives, be in - or done with - clinical testing and on their way toward marketing approval.
Concerns about inequitable access to such drugs and inconsistent policies led the agency to revamp its rules in 1997 and look at doing it again this year.
People have complained that cancer and HIV get preferential treatment when it comes to gaining access to compassionate-use drugs, few patients know the option exists, and administrative and cost-recovery policies are unclear. The FDA is hoping that clarifying its rules, raising awareness and minimizing red tape will widen the practice.
Others are worried that access to such drugs could be harmful, however.
Most drugs under development never make it to market because they don't work or aren't safe. Dispensing experimental drugs before there's sufficient data to gauge their effect can be dangerous.
"FDA must do its utmost to prevent a 'therapeutic misperception' that experimental drugs will definitely help desperate patients," Abbey S. Meyers, president of the National Organization for Rare Disorders, wrote in a letter to the agency, commenting on proposed changes to its rules.
In another comment letter, Dr. Bret Yarczower, medical director of Geisinger Health Plan, said he fears that making the drugs available will be detrimental to clinical trial enrollment.
In such trials, patients are often given placebos instead of the experimental treatments so effects can be measured, and the very ill often don't want to run the risk of getting a fake drug. If they have the option to ask for a compassionate-use drug, even if they have to pay, they might do that rather than participate in clinical trials, which are needed to gather data and eventually bring a drug to market.
Osiris made a decision to stop offering its adult stem cell drug Prochymal to adults on a compassionate-use basis once late-stage trials had begun.
"We treat children because it's the right thing to do," said chief executive C. Randal Mills, adding that the company needs "to cap it somewhere because it's not an inexpensive thing."
Mills declined to provide the exact cost.
The drug is in testing for various diseases, including Crohn's. But it's eligible for compassionate-use dispensation as a treatment for graft versus host disease, or GVHD, a deadly complication that affects about half of the 8,000 to 10,000 Americans who receive bone marrow transplants each year. Symptoms include liver disease, intestinal bleeding and peeling skin.
Osiris has given Prochymal to about 20 people in dire situations, half to children like Luis, on a compassionate basis with varying results.
Dr. Hans Klingemann, director of the bone marrow transplant program at the Tufts-New England Medical Center in Boston, learned of Prochymal at a conference in late 2005 and contacted the company when he had an adult GVHD patient who wasn't responding to other medication.
"You grab at that kind of straw," said Klingemann, who called Osiris and asked for help. They sent the drug, along with a team of people to show him how to administer it.
Klingemann's first Prochymal patient recovered well, but the second - a child whose disease was too advanced to expect much - had no response, he said. His center is now participating in the adult Prochymal clinical trials.
There are some benefits to a business offering drugs on a compassionate-use basis even if they don't recoup costs. (According to the FDA, 22 requests to charge patients are received each year.)
Osiris collects data about how Prochymal works each time. And doctors become more familiar with its product, which could make them more willing to use it if it receives marketing approval.
"They get a leg up before it's officially on the market," said biotechnology analyst Phil Nadeau of Cowen and Co. Several companies he covers have offered compassionate-use programs, including New Jersey's Celgene Corp., which in 1995 got approval for a program treating an AIDS-related wasting disorder, and California's Genzyme Corp., which has made a drug available to treat those with Pompe disease, a deadly muscle disorder.
Last month, Siga Technologies announced that it had given an experimental smallpox drug to a toddler who contracted a similar disease, after being asked to do so by the U.S. Centers for Disease Control. The New York company, which has no marketed products and had never tested the drug in humans, leased a jet and sent the drug off with its lead scientist, spokeswoman Christine Taylor said.
"We absorbed the cost," she added. The drug also improved the child's condition.
Such results are encouraging, but "it's hard to know how to interpret any data" outside of a clinical trial, said Sara Radcliffe, vice president of finance and regulatory affairs at the Biotechnology Industry Organization. She said altruism is the true driver in compassionate use.
"Generally speaking, it would bring very little benefit to the company to provide the product," she said. "On the other side, though, these companies believe in their products. And when you have somebody on the phone - and I talk to companies all the time who have this happen - who says my wife, my husband, my child has been told that he or she has two months to live ... as human beings that is a wrenching situation to be in. You want to help these people."