Heart of Bureaucratic Darkness

Why won’t the FDA make a decision on a muscular dystrophy drug?

The Wall Street Journal

Opinion

Aug. 9, 2016 7:10 p.m. ET

Government ineptitude is usually a punch line, but the dark reality is that bureaucratic malfeasance can carry a body count. The Food and Drug Administration is months late deciding whether to approve a drug for muscular dystrophy, and by now there’s only one explanation: Some of the agency’s staff have exploited FDA processes to evade accountability for an unprofessional review.

Ten of 12 boys with Duchenne muscular dystrophy walk after four years of treatment on eteplirsen, which produces the protein dystrophin. FDA has pushed off approval for the first-in-class treatment, asking for more time or even months-long delays blamed on snow. In June FDA asked the drug’s sponsor, Sarepta Therapeutics, for readouts from a continuing trial, which the company said it would provide shortly. Since then, radio silence from the FDA.

It’s no secret that the drug’s detractors are career employees in the neurology division, two of whom opposed approval at a public FDA meeting in April: Eric Bastings, deputy director of the division; andRonald Farkas, a clinical team leader. The pair say the drug doesn’t produce “enough” dystrophin, or maybe any dystrophin, depending on which day you ask. Janet Woodcock, head of the drug evaluation center, can overrule the department and the recommendations of an advisory panel.

The question is whether someone in the division is holding up an approval by Dr. Woodcock with what is known as a differing-professional-opinions proceeding, which is an agency process for handling scientific disputes. According to FDA manuals, this involves a panel review that can take weeks or more, and an appeals channel can escalate to FDA Commissioner Robert Califf. This is the only logical explanation for the continuing delay, as FDA could have rejected the drug already if the data were junk. (An FDA spokesman declined comment.)

Yet the FDA manuals are clear that this bureaucratic safety valve exists for agency decisions with a “significant impact on public health.” There are an estimated 15,000 boys in the U.S. with Duchenne. Only 13% are amenable to eteplirsen, and no serious side effects have been reported. In other words, eteplirsen poses zero risk and has a de minimis impact on “public health.”

Here is one reason an FDA staffer would file a complaint against eteplirsen: To protect his job after a contentious proceeding noticed by patients, the press and several U.S. Senators. The agency manual says that “all initiators of disputes are protected from any retaliation by their supervisors, peers, leadership and others, related to initiating or engaging in this process.”

This could be an insurance policy against getting fired for “scientifically questionable comparisons” and “errors.” That’s how more than 35 Duchenne experts described one of FDA’s eteplirsen review documents in a February letter to neurology division directorBilly Dunn.

Basic mistakes include the level of dystrophin typically found in an untreated patient. FDA has suggested comparing eteplirsen boys with a cohort that appears to be from a different drug’s trial, whose participants were largely younger, often walked farther and were followed for only a year. That’s closer to anecdote than science. Dr. Farkas claimed that Duchenne boys often walk until age 16 based on data for three patients.

Some slips cannot be attributed to mere incompetence. The agency asked an advisory panel to vote on 50-word questions littered with jargon, instead of a straightforward yes or no for approval. Yet FDA guidance prescribes “minimal qualifiers” and phrasing that reduces “any potential confusion.”

Then there’s news last month that the division refused a request for accelerated approval for a Duchenne drug by the Swiss companySanthera Pharmaceuticals. That treatment boasts statistically significant results in a large, randomized trial, the results of which appeared in The Lancet. But the division’s message seems to be: Don’t even try to cure this disease. Millions in research funding will flow elsewhere as a result of this regulatory intransigence.

***

Drs. Farkas and Bastings have lost the public’s confidence that they can conduct a fair review, and no bureaucratic proceeding should stop the FDA from reviewing their fitness for service. A cleaning out is overdue: The neurology division takes 600 days on average to approve a drug, according to a Manhattan Institute analysis. That’s three times the figure for the oncology division, which is hardly known for promptness, and neurology’s workload is below average for the agency.

FDA could issue a decision in a day or in a month, and no one knows. Meanwhile, parents with Duchenne children are swallowing decisions like: Should I enroll my son in a risky clinical trial when a drug that works might be approved any day now? What’s hideous is that parents are forced to make choices based on the little they can glean about a dysfunctional bureaucracy.

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