It is a dilemma that the federal government has given its own special name, “compassionate use.” From the point of view of the Fowlers, it would be compassionate indeed if Shire, an Irish-based drug company that has a rare diseases division in Lexington, Mass., agreed to provide the drug that potentially could save their child.

So began an encounter that provides a window into one of the most heart-wrenching dilemmas in modern medicine: should an experimental drug be given to a dying patient if it is unproven and might unravel a carefully designed clinical trial?

WASHINGTON — Jamie and Jason Fowler arrived early at a Chicago airport hotel on a recent Saturday morning, eager to meet the pharmaceutical executive from Massachusetts they hoped would help save the life of their 6-year-old son, Jack.


“Jason and I made a promise the day Jack was diagnosed that we would do everything and anything possible to ensure he is happy, healthy, and living,” Jamie Fowler said. “It’s a living nightmare to ride this roller coaster of hope and fear, hope and fear, and then trying to find the strength within all that.”

But from the point of view of the company, which wants to both save lives and produce a profitable drug that receives the blessing of the Food and Drug Administration, the risks of providing a drug in the early stage of testing can be high.

“This is an extremely difficult situation for all of us, and I felt it was the right thing to do to meet with them and give them the opportunity to speak face to face,” said Flemming Ornskov, a Danish-trained pediatrician turned chief executive who is based in Shire’s Massachusetts headquarters. The company’s website has this motto: “To be as brave as the people we help.”

The backdrop of the meeting between the Fowlers and Ornskov underscored the stakes.


The FDA first allowed patients facing life-threatening diseases access to promising investigational drugs outside of clinical studies in 1987, amid the AIDS crisis. But the regulatory agency cannot mandate that drug companies provide the unproven therapies.

An FDA spokeswoman said that of the 940 submitted requests for compassionate use in 2012, all but four cases were allowed to proceed.

Medical ethicists and rare-disease patient advocates say it is virtually unheard of for a company to grant compassionate use of experimental drugs before knowing if a drug is effective, because of the fear that an adverse event could slow or halt FDA approval. While the agency says it does not hold an adverse event such as death against a drug’s chances of approval, companies do not want to take the risk.

A delay in a drug’s approval can ultimately hurt patients awaiting the benefits it could provide.

In addition to jeopardizing their chances of FDA approval, companies also worry about maintaining an adequate supply of the drug for clinical trials. Then there’s the potential of undermining their trials if more patients seek compassionate use rather than participate in a trial and risk being assigned to an experimental group where they may not receive the drug.

“These are among the hardest ethical challenges out there,” said Arthur Caplan, a bioethics professor at New York University Langone Medical Center. “It is heartbreaking for the family, but weighing against that are other people who may benefit from the drug getting to market. The earlier the drug is in the process, the harder it is to know what to do.”


Facing a long, slow decline

Jack Fowler, 6, has a severe form of Hunter syndrome, a rare metabolic disease that causes physical and mental impairments and affects an estimated 2,000 patients worldwide. John Zich for the boston globe

The Fowlers' son was diagnosed with the severe form of Hunter syndrome when he was 15 months old, after his parents became concerned that he was still not sleeping through the night and never learned to roll over or crawl. Tests indicated that he was missing a gene that makes an enzyme needed to break down complex sugars.

The rare metabolic disease affects an estimated 2,000 patients — nearly all boys — worldwide; about 400 to 500 are in the United States. Some children experience only physical impairments, but most, like Jack, have cognitive impairments as well that, if untreated, will cause their mental and physical abilities to regress over time.

The once chatty boy spoke his first word, “mom,” at nine months — a moment Jamie Fowler proudly documented in his baby book. Jack’s language development topped out at three-word phrases when he was 4 years old.

Now he’s down to just a few single words. But he no longer calls his 2-year-old sister, Juliet, “sis.” And he’s stopped naming his friends.

Each night in their suburban Chicago home, Jamie and her husband show him pictures of extended family members, touching their faces and repeating their names in hopes that he won’t forget.

Jack no longer understands one-step directions, like fetching his shoes. He eats with his hands, instead of utensils. And he’s still in diapers.


Shire, a global biopharmaceutical company that markets a broad range of treatments, is testing the safety of a new drug that would be injected into the spinal fluid in hopes it will distribute through the brain and slow mental deterioration. The Fowlers wanted Jack to be part of that trial, but he was disqualified because of increased pressure around his brain that could put him at greater risk for an adverse outcome. That left his parents trying to get the drug by arguing that Shire should provide it through a “compassionate use” program.

Researchers hope to begin testing the drug’s effectiveness within a couple of months. The trial is scheduled to last one year and analyzing the results will take an additional six months. Then, if the data shows it is effective, the FDA must conduct its own reviews and, if it agrees with Shire, grant approval.

In all, it could be two to three years, at best, before the drug comes to market, said Dr. Joseph Muenzer, a pediatrics and genetics professor at the University of North Carolina at Chapel Hill who is the principal investigator for the drug’s US clinical trial, and who is familiar with Jack’s case.

“By then, [Jack] will lose more abilities and at some point, it may be irreversible,” Muenzer said. “I can’t blame them for trying but compassionate use would just destroy a trial. Once you give it to one, what about the next family? And there will be a next family.”


Muenzer and other rare disease advocates say the FDA needs to develop new criteria to make it easier for drugs that treat rare disorders to be approved, because there are so few patients to draw from for clinical trials.

Congress in 2012 passed a law requiring the agency to issue rules that would allow rare disease drugs access to an accelerated approval process. The new rules are still being written.

“From a regulatory perspective, Shire is caught in a bind,” Muenzer said.

Hopes swiftly dashed

At the airport hotel, Jamie Fowler clutched a striped gift bag containing a framed photo of a smiling Jack, at age 3, before disease stripped him of his ability to string words together — and one of him now, a quiet kindergartner with deep-set blue eyes and dimples. She hoped that the CEO would hang the photos in his office as a reminder of the patients whose lives Shire can save.

The Fowlers’ hearts sank at the sight of three security guards hovering by the conference room door. They exchanged awkward handshakes with two Shire executives, and sat across from them at a long table.

“If Jack had words, he would say, ‘Be brave,’” Jamie Fowler recalled telling the CEO.



It quickly became obvious to the Fowlers that Shire would not budge. Three minutes later, the parents walked out.

The brightly striped gift bag sat on the conference table, unopened.

Phil Vickers, global head of research and development at Shire, said in an e-mailed statement to the Globe that giving the drug would be irresponsible and unethical, carrying risks that could prevent other Hunter patients from eventually benefitting. “While we are deeply sympathetic to the family, it would be ethically wrong to put the request of a single patient above the hoped benefit to the greater Hunter syndrome community,” he said.

The Fowlers are still waging a public fight. They’ve compiled two thick binders containing more than 32,000 signatures petitioning Shire. They enlisted more than 700 supporters using social media to e-mail Shire directly. And on a recent Monday, hundreds more flooded the CEO’s office with phone calls.

Jack’s doctors expect he will end up in a vegetative state as his central nervous system degenerates in coming years. He will gradually lose the ability to walk, talk, swallow, and eventually, breathe. It would be unusual if he lived much beyond the age of 15.

In the evenings, Jamie Fowler lies next to her son in his pirate-themed bedroom, until he falls asleep.

“He still says ‘mom.’ But every night, I think, if he loses that word . . .” She could not finish her sentence.

Jack does still say “birfday.”

So his parents celebrate, as many times as they can. All year round.

Tracy Jan can be reached at tjan@globe.com.