Tuesday, August 2, 2011

How a Well-Intended FDA Policy on Colchicine is Harming Patients

The road to hell is paved with good intentions.

The FDA has reaffirmed the truth of this aphorism with its policy about Colchicine. Here's the story:

I recently spoke with a friend who has a family member suffering from Familial Mediterranean Fever (FMF), an auto-inflammatory disorder, most commonly seen in eastern Mediterranean populations. The condition is characterized by recurrent painful inflammation of the abdomen, chest and joints, accompanied by fever. FMF is associated with mutation of a gene on chromosome 16 involved with regulating Pyrin, a protein that is part of the inflammatory response. There is no specific test for the disease. Diagnosis is made on the basis of symptoms, family history, and ruling out other conditions.

Since the 1960s, Colchicine, a plant extract first used for treatment of gout two thousand years ago, has been used for treating FMF. As an ancient treatment widely used prior to formation of the FDA, Colchicine did not require FDA approval as a new drug.

In 2009, the FDA granted approval to URL Pharma for Colcrys, its version of Colchicine, based on randomized controlled trials the company conducted. Because Colchicine had never been subjected to the FDA approval process, Colcrys was, in a technical sense, a "new" drug approved for a "new" indication - treatment of gout and FMF - despite the centuries of prior use.

Here's where the well-intended harm comes in. The FDA is allowed to give market exclusivity to a new drug for new indications, as an incentive for pharmaceutical companies to conduct tests and seek FDA approval. In September 2010 the FDA did just that - it ordered all other manufacturers to cease production and marketing of their versions of Colchicine.

Generic Colchicine cost ten cents per dose. Colcrys costs close to five dollars. The company defends the price increase as (a) necessary to support its research and (b) offset for vulnerable patients by a support program for circumstances of hardship.

The FMF community, however, has documented that FMF patients respond differently to different preparations of Colchicine. Apart from the financial impact of a fifty-fold price increase, many who were stable on a previously available form of the drug relapsed on Colcrys.

That's what happened to my friend's family member - a series of severe fevers and inflammatory reactions, leading to emergency room visits and hospitalization.

An editorial in the New England Journal of Medicine argued that URL Pharma's research added no significant benefit to public health of the kind that would justify the reward of market exclusivity. (See here for a vigorous response from URL Pharma.) But apart from the financial hardship market exclusivity creates for patientr and insurers, banning the alternative forms of Colchicine injures patients who respond to those forms and not to Colcrys.

My friend is resourceful, and was able to find "contraband" Colchicine. When it was administered, it did the job for his family member.

Encouraging research and true innovation is a social good. But so is preventing recurrences of FMF! A policy that does not allow exceptions to prevent avoidable harms is an unethical policy. Given that alternative forms of Colchicine are no longer manufactured and sold in the U.S., the FDA should make provision for importation from abroad for patients like my friend's family member.

(See here for an excellent article on FMF and the impact of the FDA policy by Dr. Janine Jagger, an epidemiologist who suffers from the condition.)

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