FDA seeks to withdraw Shire drug

In a move that may be intended to prove its seriousness about plans to get tougher on post-marketing oversight of pharmaceuticals, the US Food and Drug Administration (FDA) is proposing that Shire's orthostatic hypotension drug ProAmatine (Midodrine Hydrochloride), as well as generic versions of the product, should be withdrawn from the US market due to the company's failure to complete post-marketing studies proving a clinical benefit.

The FDA's proposal marks the first time that the federal agency has moved to pull a drug from the market due to a manufacturer's failure to complete the required post-marketing studies.

Shire won approval for ProAmatine, whose active ingredient is midodrine, nearly 15 years ago under the FDA's accelerated approval programme, which allows approval based on surrogate endpoints for drugs that treat serious or life-threatening diseases. The conditions of the approval stipulated that Shire had to verify the drug's clinical benefits, such as improvement in patients' ability to perform life activities, through post-marketing studies.

However, neither Shire nor any of the manufacturers of the generic versions of the drug have ever completed the studies, despite pressure from the FDA, according to the federal agency. Generic versions of ProAmatine are made by Apotex, Impax Laboratories, Mylan, Sandoz, and Upsher-Smith.

"We've worked continuously with the drug companies to obtain additional data showing the drug's clinical benefits to patients," said Norman Stockbridge, director of the Division of Cardiovascular and Renal Drugs in the FDA's Center for Drug Evaluation and Research.

The FDA has given notice to Shire that the company must respond to the agency within 15 days if it wants a hearing on the matter. If Shire does not request a hearing within that timeframe, none will take place. Meanwhile, the generic manufacturers have 30 days to submit written comments. "If, after considering any relevant submissions, the FDA continues to believe that withdrawal of approval is warranted, approval of all midodrine products, including generic versions, will be withdrawn," the FDA said.

ProAmatine and its generics are not huge money-makers for the companies, and so the manufacturers may opt simply to let the FDA take the products off the market without a time-consuming and expensive fight. The FDA estimates that about only about 100,000 patients in the US filled prescriptions for brand or generic forms of midodrine in 2009.