The Magazine

Can This Boy’s Life Be Saved?

The answer may depend on President Obama.

Mar 24, 2014, Vol. 19, No. 27 • By MICHAEL ASTRUE
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The January 31, 2014, Boston Globe front page included two life-and-death stories. One announced that the U.S. Department of Justice would seek the death penalty for Dzhokhar Tsarnaev, who is facing trial for the Boston Marathon bombing. Animated debate about the proper penalty for Tsarnaev continues around Boston.

John Zich

Jack Fowler at home with his parents and sister

John Zich

The other story snapped my head back because it involved a death penalty for Jack Fowler, a 6-year-old boy dying of the more virulent form of Hunter syndrome (also known as MPS-II). The drug he needs to survive, which he is being denied, is one that I had first proposed in 2003 when I was CEO of a small biotech company focused on rare diseases. In 2005, after two years of developing this drug, Shire Pharmaceuticals bought my company over my objections, and I lost touch with the program. Jack’s situation is particularly compelling, but hardly unique.

Hunter syndrome is a simple disease that, absent a spontaneous mutation, kills only boys because the genetic defect occurs in the male chromosome. It is in a class called lysosomal storage diseases in which the absence of one gene on a chromosome means the body cannot produce an enzyme that clears certain cells of a substance that eventually kills those cells. The timing and details of a patient’s deterioration depend on which types of cells the particular disease damages, but without treatment in almost all cases the missing enzyme causes a painful death, usually at a young age. 

Every program to address a lysosomal storage disease with enzyme replacement therapy has been at least partially successful, with minimal safety risks. These days it is not a big deal from a technical perspective to make the missing enzyme and then infuse a patient with the enzyme. Shire has been hugely successful with Eleprase, an enzyme for Hunter taken through Phase III trials by my old company.

Hunter syndrome, though, has a particularly insidious twist. The enzyme the FDA approved for intravenous administration substantially cures half of the patients. For reasons that are unclear, for the other half the disease attacks the brain as well as the body, and the blood-barrier prevents the enzyme from reaching brain cells. The unlucky boys can function well for their first four or five years, but then slowly lose mental capacity, and then lose control of their bodily functions. They usually die a horrible death between the ages of 10 and 15.

I believed that we could save these children by reformulating the enzyme so that it could be injected a few times each year directly into the brain or spine, even though the FDA had never approved a biologic drug for that route of administration. At the time I lost the battle for my company, I thought that Shire would terminate this program. To Shire’s credit, it persisted.

Progress with the new version of the enzyme has been slow. Shire reported positive results from a Phase I/Phase II safety and dosing trial, and is now accruing patients for the pivotal trial it hopes to submit to the FDA for approval. Jack Fowler’s parents tried to enroll their son in the trial, but he did not satisfy at least one of the entry criteria. The Fowlers then asked Shire to support their physician’s application to the FDA for “compassionate use” of the drug; to their surprise, Shire refused.

Boston yawned at the second death penalty story, so I called up a thoughtful friend with a national radio show, Dan Rea, and asked him to try again. He was moved by the Globe article, and he put Jack Fowler’s parents on the air for an hour. You can listen to a podcast of their emotional discussion at www.boston.cbslocal.com/show/nightside-with-dan-rea.

Dan asked the Fowlers the pivotal question: Why would anyone not try to save their child’s life? They struggled with that question and chalked it up to ignorance and greed. While I do not know Shire’s state of mind, I think the most likely explanation—and the explanation in many other similar cases—is that the company is worried about antagonizing the FDA.

For decades the FDA has had an uneven track record when it comes to administration of its compassionate use programs. Some examiners work heroically with families, physicians, and companies to get an experimental drug to patients who will otherwise die soon. Other examiners are callously wedded to their standard processes and will threaten companies if they dare to ask about a compassionate use exemption. 

What’s worse is that compassionate use has become an entitlement of the Washington elite; for instance, if you are a relative of a member of Congress seeking a compassionate use exemption, you can expect that an FDA official will immediately call the company in question to demand that it submit and support an application for compassionate use. I was on the receiving end of those calls several times in the 1990s when my employer was in a final trial for an experimental anticoagulant, which at that time was uniquely life-saving for certain surgery patients allergic to heparin.

At any given point of time, there are thousands of patients like Jack Fowler who need a drug based on a clear mechanism of action that has a clean safety trial prior to a pivotal trial. Jack’s parents have declared that they would do what any decent parents would do, and they would sign a waiver of liability that would shield Shire from any lawsuit. A hospital ethics review board would have to review Jack’s particular case and determine that it is ethical for Jack’s doctor to prescribe the drug for him. If those things happen, there is a real chance Jack will live. If those things don’t happen, it is all but certain that Jack will die what all constitutional lawyers would consider a “cruel and unusual” death.

President Obama should end this standoff right now. First, he needs to call FDA commissioner Margaret Hamburg and make sure that there are no facts outside of the public domain that would make Jack Fowler a poor risk for a compassionate use exemption. Second, assuming that conversation goes as it most probably will, President Obama should ask Commissioner Hamburg to pick up the phone and call Shire’s new CEO, Dr. Flemming Ornskov, and tell him that whatever his nervous regulatory executives are telling him is untrue, and that the FDA would genuinely welcome their support of a compassionate use application for Jack Fowler.

Almost surely, that phone call will save Jack from a death penalty that is the indirect product of a nontransparent and unpredictably administered regulatory process. It is important, though, that President Obama not stop there; his time is too valuable to keep making these kinds of calls.

President Obama should have his lawyers draft an executive order that will keep sick children off Death Row. In that order he should direct the FDA to convene an advisory committee with several ethicists and a hefty dose of patient advocates to advise the FDA on a public list of experimental drugs presumptively approvable under the compassionate use exemption. The current compassionate use rules, which were thoughtfully revised under this administration, are fine as far as they go, but they do not address the nontransparency that enables unpredictable decisions that cause unnecessary deaths.

President Obama can do something heroic if he simply shows his respect for human life by directing that life-and-death decisions under his control are made openly, honestly, and compassionately. He does not need new legislation—it is just a question of using the authority he already has.

Surely, even with all our political divisions, every decent person in Washington can get behind saving the Jack Fowlers of our nation.

Michael Astrue served as HHS general counsel (1989-1992) and commissioner of Social Security (2007-2013). He was a senior vice president and then CEO of the rare disease company Transkaryotic Therapies from 2000-2005. He has not spoken directly or indirectly with Shire, the FDA, or the Fowlers about this case.

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