FDA on Monday announced that it was looking to withdraw approval for the low-blood-pressure treatment midodrine hydrochloride because the companies manufacturing the drug failed to provide data from post-approval studies.

The kicker: The drug was approved 14 years ago.

FDA gave midodrine hydrochloride—branded by Shire as ProAmatine and produced by a half-dozen generics firms—the green light in 1996 as part of the fast-track approval program designed to speed to market drugs for diseases with no current treatments.

The catch is that FDA requires post-market clinical trials to ensure that the drug is meeting risk/benefit endpoints. In other words, the regulatory body wanted to make sure no hiccups occurred with the treatment when it hit the general population.

In response, Shire—who acquired the drug when it bought Roberts Pharma in 1999—chose to withdraw the drug as of September 30. The drug firm made it clear that the withdrawal had nothing to do with any safety concerns. In addition, Shire stated that it had conducted post-market trials in conjunction with Roberts, but FDA felt the results were “inconclusive.”

According to a release by FDA, none of the companies selling the drug have provided any data to prove that the treatment is beneficial. That said, some 100,000 people were treated with the midodrine hydrochloride last year alone.

“We’ve worked continuously with the drug companies to obtain additional data showing the drug’s clinical benefits to patients,” stated Norman Stockbridge, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research. “Since the companies have not been able to provide evidence to confirm the drug’s benefit, the FDA is pursuing a withdrawal of the product.”

FDA stated that patients currently on midodrine hydrochloride should not stop taking the medication. Shire now has 15 days to respond to FDA’s inquiry and provide some data supporting the drug. Shire did not respond to calls as of Monday afternoon. In addition, it’s unclear as to why FDA waited so long to ask for more data and whether any adverse reactions have been reported pertaining to the drug.

FDA, this morning, walked media through its proposed regulations requiring that pharma companies submit post-market adverse event reports through an electronic format. This is being done to help eliminate time and cost wasted on paper submissions.

“This change will enhance FDA’s ability to rapidly identify new safety concerns and share safety information with the public,” said Gerald Dal Pan, director, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA.

Currently, FDA accepts reports in both paper and digital formats. Since 2000, CDER has allowed drug companies to submit forms electronically via a pilot program. Electronic reports are entered into a database almost immediately if logged through the FDA’s Web gateway, and take a bit longer if submitted on a CD or DVD.

“The proposed rule does not propose any changes to the requirement for what information must be reported to FDA,” Del Pan said in a press conference. “It proposes that the information be submitted electronically rather than on paper.”

Today, FDA laid out two options for electronic submissions. Manufacturers can submit via international electronic standards or through a Web based safety-reporting portal currently under development. According to Del Pan, the Web-based portal is intended for companies with small numbers of reports and for consumers to report side effects directly.

FDA said that the new regulations will improve the overall efficiency of the adverse event reporting process, and that it will cost less to input forms that come in digitally. However, the agency would not disclose the cost of upgrading to the new electronic system.

“A lot of companies are doing this already,” Del Pan said. “We currently receive between 400,000 and 500,000 reports a year, and about 80 percent of those are already coming in electronically, based on the pilot program started in 2000.”

An FDA director has come under fire by a generics firm claiming that the director of the Center for Drug Evaluation and Research favored a competitor in a wanton act of conflict of interest. The Wall Street Journal this morning broke the story that Janet Woodcock is under investigation by FDA officials, and that an official ethics complaint has been filed against the director.

The generic firm leading the charge, Amphastar, submitted an application in 2003 for approval of a generic version of the blood-thinner Levenox. In 2007, FDA rejected the drug due to potential immunogenicity concerns.  After sifting through public records, Amphastar discovered a conflict of interest between Woodcock and Momenta Pharmaceuticals—a rival firm that filed for a similar blood thinner two years after Levenox.

“It appeared [that] one of the founders of Momenta and the vice president of Sandoz, in February of 2007, were working together to define the immunogenicity standards at MIT,” Amphastar spokesperson Dan Dichner told Pharm Exec. “They sent these emails to Janet Woodcock urging FDA not to approve a generic equivalent hastily.”

Additionally, Amphastar claims that during the heparin crisis Woodcock turned to Momenta to identify the contaminant instead of using its own internal labs. Both companies’ blood thinners include Heparin, but neither firm was found to have the tainted heparin in its drugs.

The clincher was that Woodcock penned journal articles for two publications in tandem with Momenta scientists, which, according to Amphastar, caused Momenta’s stock to spike 17 percent.

“We just summarized public information, and asked Woodcock to recuse herself from the review process based on this information,” Dichner said. “The ball’s in [FDA’s] court. We’ve done everything they’ve asked. We’ve been inspected 12 times in the last year, which is unbelievable. The correspondence with the new leadership has been positive. They claim that they don’t encourage these types of industry relationships, and we hope that that’s true.”

FDA did not respond to comment by deadline.

A joint committee of three FDA advisory groups voted on Tuesday to recommend the elimination of prescription combination drugs containing acetaminophen due to a spike in instances of liver-induced toxicity.

The panel of experts, physicians, and regulators voted 20 to 17 in favor of banning acetaminophen combo drugs such as Vicodin and Percocet. They made it clear, however, that they are not calling for a ban on acetaminophen alone, or banning the narcotic component of the pain drugs—just those factors in tandem.

“The top recommendation of the committee is that the agency needs to do something to address and decrease the ‘usual dose’ of acetaminophen for OTC products and prescription combination products,” said Sharon Hertz, deputy director, Division of Anesthesia, Analgesia, and Rheumatology Products, CDER. “The usual dose that people take, whether it’s called the single dose or the maximum daily dose, should be lowered to ensure a greater margin of safety.”

With regard to prescription products, FDA said that there is a high likelihood of overdose of prescription narcotic acetaminophen products, and if those products are not eliminated the acetaminophen dose should be lowered significantly. The panel also suggested boxed warnings so that physicians will be more aware of the potential for liver damage.

“This is clearly an issue that’s been on FDA’s mind for a long time,” said Gerald Dal Pan, director, Office of Surveillance and Epidemiology, CDER. “In 2007, we looked at the results of an education campaign, and formed an internal group at CDER to examine the issue and report some recommendations. This is the result of those recommendations.”

FDA said that there is no silver bullet to reverse the trend, and that label changes and public awareness campaigns wouldn’t have solved the problem.

No Surprise

“This is not a problem that arose overnight,” Hertz said. “The problem is very complicated and has multiple components. There probably isn’t one thing that will reverse the trend of acetaminophen-related liver toxicity. In addition, all of the components of the problem are moving at the same time that use patterns are changing. New products are coming and going from the market, and different patterns of prescribing are occurring.”

OTC combination drugs such as NyQyil are not in question, Nelson said, because data showed indicated many deaths each year from prescription combination products, and deaths from OTC treatments are far lower.

“Based on that epidemiology, you get more bang for the buck by eliminating prescription drugs,” Nelson said.

FDA is now going to back and look at the discussion and decide whether they want to move on the advisory panel’s suggestion. Pharma companies are being encouraged to change their labels and address dosage quantities before FDA announces any changes.