ST. PETERSBURG, Fla. — The drug that Alyssa Luciano fought so hard to get for her little girl was ready. Two nurses held syringes. Together, they counted down: 3, 2, 1.
Then they jabbed the needles into Avalynn’s chubby thighs. The sobbing 2-year-old shrieked even louder.
Though it was tough to listen to her baby wail, Luciano knew this medicine was essential for wiping out any last leukemia cells lurking in Ava’s body. She had been told by every authority she could reach — the manufacturer, federal regulators, scores of hospital pharmacies — that it was unavailable. But she’d refused to take no for an answer.
So now, here she was, soothing Ava — and, she hoped, saving her life.
The drug, called Erwinaze, is one of a small number of critical medications in short supply right now in the United States.
The Food and Drug Administration keeps a running list of drugs that are tough to obtain, often because of a manufacturing glitch or a problem obtaining a raw material. On the list right now: 61 medicines, including a patch that reduces nausea, a radioactive agent used to image the kidneys, and an injectable steroid.
And Erwinaze, to treat acute lymphoblastic leukemia.
The drug, which is used in patients — like Ava — who are allergic to the first-line leukemia medicine, is sold by only one company in the world, Jazz Pharmaceuticals, of Dublin. A contractor for Jazz encountered a problem when making Batch 178 of Erwinaze and quality control inspectors discovered that unknown “particulate matter” had contaminated it.
The drug couldn’t be given to patients. And no other batches were ready: They take nine months to brew. It would soon be unavailable.
The Florida hospital treating Ava — Johns Hopkins All Children’s Hospital, here in St. Petersburg — had a small supply of Erwinaze in stock.
But then a 7-year-old boy suffered an unexpected relapse of his leukemia. He got the last precious doses.
And doctors had to tell Luciano they had no more of the drug for Ava.
Luciano was glad the little boy got his medicine; she knew his family and understood how much he needed it. At first, she thought it would just be a day or two before the hospital got in more doses for Ava. But on the Friday afternoon before Columbus Day weekend, her internet research turned up reference after reference to shortfalls of Erwinaze, and the former third-grade teacher began to panic.
“I was taken aback. I didn’t dream that it was going to be a real shortage,” she said. “I started to freak out that evening.”
Luciano spent most of the weekend on the phone, calling more than 100 hospital pharmacies — in every US state, plus a few in Canada.
No one had extra doses of Erwinaze in stock.
Desperate for updates, she tried the FDA at least once a day. On Facebook, she tracked down the CEO of Jazz, and he connected her to company officials. She spoke with them two, three, four times a day, her panic rising as she realized that no one had a supply of the drug.
Ava had already missed one dose of Erwinaze, on the Friday before the long weekend. She was due for three infusions the following week.
Ava missed her Monday dose. Then her Wednesday dose.
Luciano kept calling.
Friday came and went.
Four missed doses.
The doctors couldn’t say if the lapse in treatment would affect Ava. They hoped not. But no one could say for certain. Researchers who’d studied the drug had never considered such a scenario.
A little girl falls ill
Ava’s illness had come on suddenly.
A few days before Christmas last year, shortly after her second birthday, Ava took a tumble and stopped walking. Luciano took her for X-rays, but the doctor couldn’t see anything on the scans and promised she’d be back to her old self within a few days.
Over the holidays and through most of January, though, Ava kept getting worse. She stopped sitting up. She complained that it hurt when her mom brushed her straight blond hair. Her eyes swelled and her limbs bruised. Her nights were interrupted with sweats and fevers.
Doctors kept telling Luciano that she was overreacting, that Ava would be fine. She just had an injury. A cold. A harmless black-and-blue mark.
On Jan. 30, Luciano put all the symptoms together in her mind for the first time, and suddenly knew with grim certainty what they were dealing with. The son of a friend of a friend had been diagnosed with leukemia, and he’d had all the same symptoms.
Luciano convinced doctors at a nearby urgent care center to test Ava’s blood. The second they got the results, they urged her to rush the toddler to the hospital.
After 10 minutes at All Children’s, Ava was diagnosed with acute lymphoblastic leukemia. Doctors kept her in the hospital for a dozen days as they doused her leukemia cells with high-dose chemotherapy. She went home, only to spike a fever. Another 11 days in the hospital.
Once a death sentence, this form of leukemia is now considered extremely treatable. About 3,100 children in the US are diagnosed each year, and more than 85 percent go on to live a normal life.
The treatment, though, is long and grueling, lasting up to three and a half years.
Ava, like many patients, had heavy chemotherapy first, to knock her disease into remission. A crucial next step is a drug like Erwinaze, which would starve any stray leukemia cells in her body of necessary nutrients. Treatment regimens vary, but Ava was scheduled for 36 doses. The family was billed about $900,000, paid by her insurance, though the company said it billed the hospital less than $240,000.
It’s hard to say how many patients need Erwinaze, because it’s considered a backup to the first-line treatment. But it’s not a small number: ALL is the most common type of childhood cancer, and as many as 1 in 3 patients is allergic to the more commonly used drug, PEG-L-asparaginase.
“We’re in a world where we don’t have a lot of backups and it doesn’t take a lot to really throw the system off,” said Dr. Colin Moore, Ava’s doctor. “We don’t have a backup for the backup.”
No option but a tainted drug
Drug shortages in the US reached a crisis in 2011, when some 251 medications were unavailable, in many cases because of manufacturing problems. The following year, Congress passed a law requiring companies to warn the FDA at the first sign of trouble. After receiving such notification, the agency works with manufacturers to try to find a solution. Thanks in part to the new system, the number of shortages fell to 26 last year.
But they still happen.
Indeed, the complexity of the modern drug manufacturing process makes it nearly impossible to ensure that all vital drugs will be available at all times.
“It’s hard to make a sterile injectable [drug],” said Valerie Jensen, associate director of the drug shortage staff at the FDA’s Center for Drug Evaluation and Research. “From start to finish, that product needs to remain sterile and free of particulates. Things can go wrong — and do go wrong.”
Erwinaze has been on the shortage list since Oct. 14. Toward the end of the month, federal regulators came up with a work-around that would allow Jazz to release the tainted batch of Erwinaze — with stringent controls.
Pharmacists have to check vials of Erwinaze to make sure there is no visible contamination. Then they must add saline to the powdered drug, and pass it through a filter.
The drug is easiest to deliver by IV. But because of fears that the particulate matter could get into a patient’s bloodstream, the FDA is requiring doses from Batch 178 to be injected directly into the muscle. It’s a lot more painful for patients. But regulators deem it safer.
Jazz’s Chief Medical Officer, Karen Smith, said she’s not sure when the next batch of Erwinaze will be ready, or when the drug will be able to be delivered again through an IV.
But the workaround has helped: The FDA is expected to take Erwinaze off the shortage list this week, though Smith said supplies may continue to be tight for a while.
“We feel for every patient and every parent in this situation,” she said.
A mother finds her voice
Luciano is still haunted by those six weeks last winter when no one believed her that Ava was sick. She wonders if Ava’s treatment would have been easier, remission achieved faster, if her diagnosis had come sooner.
Anger at that feeling of powerlessness may have pushed Luciano to be more vocal about the Erwinaze shortage — to make all those phone calls to hospitals and regulators and company executives.
“That’s what probably fueled this,” she said. “It has given me a voice that I will never not listen to.”
For now, she’s focused on getting Ava through the rest of her treatment. Ava has six more doses of Erwinaze left — the hospital now has them all in stock — to be administered over the next few weeks. Then she’ll go on a maintenance drug, which she’ll likely take through next May.
The Erwinaze shots are so painful that they leave Ava’s legs burning for about a half-hour after each injection.
“Hopefully she won’t even remember,” Luciano said. “She won’t remember when she was really sick the way I will.”
Her little girl is now so familiar with All Children’s, she acts as though she owns the place. On a recent weekday, she marched into her appointment clutching “Baby,” a blonde-haired doll, whom she had recently awakened from a nap. Ava insisted that Baby get weighed and measured when she did.
“She’s got quite the personality,” Luciano said. “She’s a little difficult to contain.”
Ava flitted around during the hour she waited for her treatment. She colored. She watched cartoons. She took a plastic dog for a walk around the chemo stations.
Spending so much time in a hospital seems commonplace to her now. She thinks everyone has a port for delivering medicines. And her bald head matches her daddy’s; he’s a police detective who lately has kept his head shaved in her honor.
Luciano said she and her husband are going to try for another child eventually — for Ava’s sake. Nursing her through treatment has brought the family closer together, but eventually, Luciano knows she will have to give her daughter some space.
“You think you’re obsessed with your kids before,” she said. “It’s a completely different bond when you have come close to losing them.”
This post has been updated with more details on the pricing of Erwinaze.