Here's a forgotten chapter from pharmaceutical history. The acne drug, Accutane, manufactured by Roche Pharmaceuticals, has been associated with hundreds of birth defects. Since 2005 the iPLEDGE program has required that patients, doctors, and pharmacists register and that patients prove they are on birth control before they can be prescribed this potentially dangerous drug. But it wasn't always that way.
Accutane was initially listed as a category C drug for risk of birth defects, meaning that it was only of moderate risk. Moderate risk means that there are some studies in animals showing birth defects, but it isn't clear that it is really relevant to humans. When Accutane came out on the American market, after being rushed through the FDA approval process, the PDR said only that women "should not" get pregnant while on Accutane. There was no requirement that doctors test for pregnancy, or that women take birth control.
Accutane hit the media and was hailed as a wonder drug. Sales soared far beyond the wildest expectations of Roche executives. Soon every girl with pimples was demanding that pill that her school-mate got that had made her blemishes vanish away.
But not everyone was so sanguine. The Europeans weren't impressed by Accutane. It was banned in Sweden and Italy and sharply curtailed in other countries, because of the risk of birth defects associated with the use of Accutane.
If there were any birth defects in the European trials, were they reported to the FDA?
Nobody seems to remember. Hmm...
Over a decade ago in a newspaper called the Columbus (Ohio) Dispatch, Mark Somerson reported on this story in a series of investigative journalism articles. Remarkably this story about a drug that was equally dangerous as thalidomide never made it beyond the shores of the Wabash River.
Thanks
Here's a scoop for you guys, Mike and Juliet, to add to your ongoing Accutane 'investigations'!
It wasn't only the Europeans that were wary of Accutane. Some American dermatologists were as well. In fact, Frank W Yoder, MD, who with Greg Peck MD was the first to report on the use of isotretinoin for the treatment of acne in 1977, long before Roche picked it up, warned against the dangers of the drug in the January 1983 edition of the Journal of the American Medical Association, saying that "the potential toxicity of this drug has been seriously underemphasized." Both American doctors and scientists working for Roche later testified that is was known before it came out on the market that Accutane potentially had a very dangerous risk of birth defects, based on the fact that it was derived from Vitamin A related compounds, well known for many years to cause birth defects in women. Yoder and another doctor involved in the US trials remembered discussing birth defects that occurred during the European trials, although exact names of individuals involved were never produced.
In fact, Roche had known about Accutane for years before the American dermatologists had written about it, but did nothing with the drug. Somerson reported that Dr Werner Bollage, a scientist with the company, wrote in 1971 that it was "inconceivable to develop an agent" that caused birth defects for such a "common complaint as acne."
For their US clinical trial in the early 1980s, Roche required that all women get tested for pregnancy, and one woman who got pregnant was advised to get an abortion. However, once the drug went on the market, this was no longer required, according to reporting by Somerson.
Henry H. Roenigk MD, another dermatologist who had been involved in the US Accutane trial, was quoted as saying that he published a letter in the May 1982 edition of the journal Dermatology warning of the risk of birth defects, and stating that there had already been birth defects with Accutane (presumably in Europe). Following this Roche wrote a letter to all doctors who had been involved in the US trial and told them not to "divulge trade secrets."
Nine months after Accutane went on the market in May 1982, babies with birth defects started to appear.
In Sept 8 1983, after the first US birth defect cases were reported, Health Research Group wrote to the FDA urging them to require pregnancy tests and not to bury the warnings about birth defects in the "fine print" at the end of the product labeling.
By 1988 the FDA estimated there could be as many as 1,300 babies born with birth defects because of Accutane. Some of the babies were so deformed that they died in pain after only a few years of life in an institution. Probably many times more babies had mild cognitive defects. And what is worse, despite all efforts, rates of birth defects never went down until iPLEDGE.
No one deserves that, for any reason.
Doug Bremner MD is author of Before You Take That Pill