(Martha Rosenberg )
It announced it was seeking approval to market asthma drug Singular to 2-year-olds.
And it predicted 40 million women would take its new osteoporosis drug, the bisphosphonate Fosamax, as it continued to “help educate both physicians and patients” about the bone disease.
Of course Vioxx was withdrawn in 2004 for doubling stroke and heart attacks in long-term users, Singular is suspected of causing suicide, and Fosamax is tightly linked to osteonecrosis, atrial fibrillation, intractable pain, and now cancer.
While everyone knew Fosamax (alendronate) and the esophagus didn’t mix—patients who don’t remain upright for half an hour after taking it risk inflammation, ulcers, bleeding, intestinal blockage, and sometimes perforation—no one expected the salvo from the FDA which appeared in the Jan. 1 issue of the New England Journal of Medicine.
“Crystalline material similar to ground alendronate tablets has been found in patients with erosive esophagitis, and persistent mucosal abnormalities have been noted in some of these patients, suggesting a potential for carcinogenic effects,” wrote Diane Wysowski of the FDA’s division of drug-risk assessment.
In fact, there have been 23 reports of Fosamax-associated esophageal cancer in the United States and eight deaths, writes Ms. Wysowski. Europe and Japan have had 27 cases of esophageal cancer associated with Fosamax and similar drugs, with six deaths.
And while most people knew Fosamax could cause osteonecrosis of the jaw (ONJ or jawbone death)—dentists and the FDA reported it in 2004 though Merck didn’t label it until 2005—few expected the definitive study in the Jan.1 issue of Journal of the American Dental Association, which said “even short-term oral use of alendronate led to ONJ.” Oops!
Like Vioxx which was launched a month early thanks to its collegial relationship with the FDA, Fosamax was rushed to market in 1995 six months after its application on the basis of two three-year studies.
Why hold up profits for mere testing? Merck may have had to pay $4.85 billion in 2007 to settle with 140,000 Vioxx victims—but it still made a profit on Vioxx.
So no one was surprised when Merck had to send a Dear Doctor letter about Fosamax: “Since market introduction some of these [esophageal] side effects have been of greater severity than we observed in our controlled clinical trials,” said the letter, just months after approval.
In fact, the FDA threatened to revoke its act-in-haste approval over the emerging esophageal side effects, says Fortune magazine, but the head of Merck research at the time, Edward M. Scolnick, “wrote to doctors, in his own hand, explaining the causes.” He convinced the FDA “to let Merck keep Fosamax on the market, albeit with a warning label that told patients to sit upright for an hour after taking the drug.”
Thanks to Merck’s “osteoporosis awareness campaign,” which included placing of its own bone density measuring machines in doctors’ offices in the 1990s, the number of people “at risk” for osteoporosis grew from half a million to 3.6 million.
But in addition to questions about osteonecrosis, esophagitis, irregular heartbeat, and other side effects, there were questions about Fosamax’s very action as a “bone-strengthening” drug.
Was Fosamax’s anti-bone remodeling action that was supposed to stop or prevent osteoporosis actually making the bone more brittle and fracture-prone because bone was not being “turned over”?
“We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy,” began a study in the August 2008 Journal of Clinical Endocrinology & Metabolism.
“An Emerging Pattern of Subtrochanteric Stress Fractures: A Long-Term Complication of Alendronate Therapy?” was the title of another in the February 2008 issue of Injury.
“Low-Energy Femoral Shaft Fractures Associated With Alendronate Use,” was the title of another in the 2008 May–June Journal of Orthopedic Trauma.
Yes, Fosamax emerged as a drug with dangerous side effects whose primary action may not even work! And it might even cause what it is supposed to treat.
Or as the old joke goes: Bad food and such small portions.
There are even questions about the “large number of giant hypernucleated, detached osteoclasts” Fosamax creates—when its bone building “works”—also in the January 1 issue of the New England Journal of Medicine.
As with Vioxx, suspicious journal articles surfaced that “sell” Fosamax like “Loss of Treatment Benefit Due to Low Compliance With Bisphosphonate Therapy” and “Consequences of Poor Compliance With Bisphosphonates.”
Posters like “Underuse of Osteoporosis Treatment in Postmenopausal Women,” authored by an “employee of Merck & Co.” were presented.
Merck-funded doctors blamed ONJ on cancer and “bad oral hygiene.”
And, since the damaging January 1 revelations about jawbone death and cancer, one Merck-associated physician, Dr. Nicholas Shaheen, director of the University of North Carolina Health Care’s Center for Esophageal Diseases, is urging people to stay on Fosamax because its “cancer risk doesn’t outweigh” its benefits.
“If the bisphosphonate gets hung up above the narrowing, it can irritate or burn the tissue around where it gets hung up. That’s because the pill never went down into the stomach, where it is very well tolerated,” he told MyNC.com.
But Merck’s audacious marketing, which includes threatening medical schools, according to Tom Nesi in the 2008 book “Poison Pills,” doesn’t matter anymore.
Fosamax’s patent ran out in February 2008, and Merck got its money’s worth.
Martha Rosenberg is a Chicago columnist who writes about public health.
