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.
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.