Her vision failed first. Then she fell asleep at school from inexplicable fatigue. Even walking proved difficult, often impossible, as she knocked into furniture and walls. It was like an electrical switch in her body toggled without warning. Some days she was in control, most she was not. Specialists were stumped.
It took three months before a general practitioner detected the shadowy, cancerous tumor that clung to 10-year-old Violet O'Dell's brain.
In the fall of 2011, a cancer physician at Seattle Children's Hospital met with Violet. He crouched, to talk eye to eye. And he told her: The rare, inoperable malignancy struck just a few hundred children each year. Most died within a year. None survived.
But doctors could offer this: An "orphan drug" — one approved for a rare disease — might slow the cancer's growth. With the drug, Avastin, Violet might live an extra month, maybe longer. The drug cost up to $50,000.
"How much would you pay to have extra time with your dying child?" Violet's mother, Jessica O'Dell, asks. "We don't make a lot of money. We knew we'd lose our home, everything we own."
For the O'Dell family, the drug's cost exceeded their annual income. For Genentech, the San Francisco-based company that manufactures Avastin, the drug brings in $3 billion a year.
The O'Dells' conundrum — a lot of money for a little time — highlights the pharmaceutical industry's unchecked profiteering from rare diseases.
Fastest growing sector of U.S. drug system
Thirty years ago, Congress passed the Orphan Drug Act as a way to lure pharmaceutical companies to develop drugs for rare diseases that had been "orphaned" — abandoned or ignored because they were unprofitable. The hope was that drugmakers would break even or post modest profits.
The act paid off, with hundreds of new drugs. But over the years, its good intentions have been subverted by the pharmaceutical industry, which has increasingly found ways to exploit this once-obscure health care niche, transforming it into a multibillion-dollar enterprise.
The law gave drugmakers financial incentives: market exclusivity for seven years, tax breaks and abbreviated testing. The freedom from competition — coupled with the ability of drugmakers to price drugs however they want — has propelled the treating of rare diseases into the fastest growing sector of the U.S. prescription drug system.
Drugs for rare diseases commonly begin in the six figures for a year of treatment. This year, one reached $440,000.
The gray area of "off-label" drug use
The law defines a rare disease as one that affects fewer than 200,000 U.S. patients a year. Most afflict fewer than 6,000, said the National Institutes of Health. But collectively, they affect an estimated 25 million Americans — about 1 in 12 people.
By law, pharmaceutical companies can market a drug only for its approved use. However, doctors can prescribe drugs, orphan or otherwise, in whatever way they choose, which is known as going "off-label." It's in this regulatory gray area that drugs officially approved for a few hundred patients can be sold to tens of thousands more.
While off-label prescriptions benefit many patients and provide freedom of choice for doctors, the practice comes with risks. According to a Seattle Times analysis of adverse-event reports, studies and enforcement records, thousands of preventable injuries and early deaths have occurred when orphan drugs have been prescribed for unlicensed use.
When Violet received her diagnosis in September 2011, she'd been rushed from the family's seven-acre farm in Sequim to Seattle Children's. Chemotherapy began two days later for brainstem glioma, located where the brain and spinal cord connect. Cancerous tentacles intertwined with healthy tissue, making it impossible to remove the tumor.
Doctors supplemented chemotherapy with Avastin, because clinical trials had shown the drug could ease symptoms and prolong life. By late spring of 2012, treatment had stunted Violet's tumor. But a month later, the tumor spread across her brain.
The O'Dells received a miracle, just not the one they most wanted. All their medical expenses not covered by insurance were paid through a program at Seattle Children's for uncompensated care. A private charity made their mortgage payments. In Sequim, businesses and a school staged fundraisers.
"It was unbelievable," Jessica O'Dell says. "We thought we'd lose everything. So many people opened their hearts."
In October 2012, Violet died in her sleep at home, surrounded by family.
Avastin, the drug that was supposed to help Violet live longer, was studied in at least 400 clinical trials over 16 years. But it wasn't until this year that a trial with more than 600 patients — the drug's first double-blind study for newly diagnosed brain cancer — found no difference in survival between those patients who got the drug and those given a placebo.