1999 was a good year for Merck.
In its 64 page annual report it predicted arthritis medicine Vioxx--Our Biggest, Fastest and Best Launch Ever!--would prevent Alzheimer's disease and colon cancer.
It announced it was seeking approval to market asthma drug Singular to two-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Of course Vioxx was withdrawn in 2004 for doubling stroke and heart attacks in long term users, Singular is suspected of causing suicide and Fosamax is tightly linked to osteonecrosis,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, blockage and sometimes perforation (see: landmine in throat)--no one expected the salvo from the FDA which appeared in the Jan. 1 New England Journal of Medicine.
There have been "reports of 23 patients in the United States receiving a diagnosis of esophageal cancer, with alendronate (Fosamax, Merck) as the suspect drug (in 21 patients) or the concomitant drug (in 2 patients)," wrote Diane Wysowski of the FDA's division of drug risk assessment, leading to eight deaths.
Europe and Japan have had 27 cases of esophageal cancer from Fosamax and similar drugs with six deaths Wysowski wrote.
And while most people knew Fosamax could cause osteonecrosis of the jaw (ONJ or jaw bone death)--dentists and the FDA reported it in 2004 though Merck wouldn't label it until 2005---few expected the definitive study in the Jan.1 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 testing a drug when it can be "tested" on first users--the public--and make money at the same time? Merck may have paid $4.85 billion in 2007 to settle with 140,000 Vioxx heart attack victims--but it still made a profit. (see: forgiveness vs. permission).
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 later.
In fact the FDA threatened to revoke its act-in-haste approval over the emerging 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" and 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 1990's, the number of people "at risk" for osteoporosis grew from half a million sufferers to 3.6 million.
But in addition to questions about osteonecrosis, esophagitis, an irregular heartbeat and other side effects--there were questions about Fosamax' 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 it was not "turned over"?
"We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy," began a study in the Aug. 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 Feb. 2008 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 might even cause what it is supposed to treat.
Or, as the old joke goes: bad food and such small portions.
As with Vioxx, slanted and suspicious journal articles surfaced pertaining to Fosamax like "Loss Of Treatment Benefit Due To Low Compliance With Bisphosphonate Therapy"--get it?--and "Consequences Of Poor Compliance With Bisphosphonates."
Posters like "Underuse of Osteoporosis Treatment in Postmenopausal Women," by an "employee of Merck & Co"--hello?-- were presented.
Merck-funded doctors blamed ONJ on cancer and "bad oral hygiene."
But it didn't really matter.
Because whatever the verdict on Fosamax's safety--from the public or medical community's perspective--its patent ran out in February 2008.
Merck got its money's worth.
In its 64 page annual report it predicted arthritis medicine Vioxx--Our Biggest, Fastest and Best Launch Ever!--would prevent Alzheimer's disease and colon cancer.
It announced it was seeking approval to market asthma drug Singular to two-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, blockage and sometimes perforation (see: landmine in throat)--no one expected the salvo from the FDA which appeared in the Jan. 1 New England Journal of Medicine.
There have been "reports of 23 patients in the United States receiving a diagnosis of esophageal cancer, with alendronate (Fosamax, Merck) as the suspect drug (in 21 patients) or the concomitant drug (in 2 patients)," wrote Diane Wysowski of the FDA's division of drug risk assessment, leading to eight deaths.
Europe and Japan have had 27 cases of esophageal cancer from Fosamax and similar drugs with six deaths Wysowski wrote.
And while most people knew Fosamax could cause osteonecrosis of the jaw (ONJ or jaw bone death)--dentists and the FDA reported it in 2004 though Merck wouldn't label it until 2005---few expected the definitive study in the Jan.1 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 testing a drug when it can be "tested" on first users--the public--and make money at the same time? Merck may have paid $4.85 billion in 2007 to settle with 140,000 Vioxx heart attack victims--but it still made a profit. (see: forgiveness vs. permission).
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 later.
In fact the FDA threatened to revoke its act-in-haste approval over the emerging 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" and 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 1990's, the number of people "at risk" for osteoporosis grew from half a million sufferers to 3.6 million.
But in addition to questions about osteonecrosis, esophagitis, an irregular heartbeat and other side effects--there were questions about Fosamax' 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 it was not "turned over"?
"We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy," began a study in the Aug. 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 Feb. 2008 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 might even cause what it is supposed to treat.
Or, as the old joke goes: bad food and such small portions.
As with Vioxx, slanted and suspicious journal articles surfaced pertaining to Fosamax like "Loss Of Treatment Benefit Due To Low Compliance With Bisphosphonate Therapy"--get it?--and "Consequences Of Poor Compliance With Bisphosphonates."
Posters like "Underuse of Osteoporosis Treatment in Postmenopausal Women," by an "employee of Merck & Co"--hello?-- were presented.
Merck-funded doctors blamed ONJ on cancer and "bad oral hygiene."
But it didn't really matter.
Because whatever the verdict on Fosamax's safety--from the public or medical community's perspective--its patent ran out in February 2008.
Merck got its money's worth.
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