Evelyn Pringle June 13, 2006
Scranton, PA: Medical professionals need to recognize that Fosamax has only been on the market for a little over a decade and other bisphosphonates for even less time. The injuries showing up now are often the result of massive marketing of this class of drugs to relatively young persons who in many cases did not need them to begin with.
Over the last 10 years, tens of millions of people have taken Fosamax believing it would prevent bone deterioration. The drug seemed safe enough at first but in recent years it has been linked to a serious disease that causes death to the bone in the jaw, called osteonecrosis of the jaw (ONJ). The disease is an extremely serious condition and symptoms include, but are not limited to:
Pain, swelling, or infection of the gums
Loosening of teeth
Poor healing of the gums
Numbness or the feeling of heaviness in the jaw
Partial or complete loss of the jaw bone
This is another case where the risks of a drug are high while the efficacy is questionable. Experts now say that Fosamax may improve bone density, but when it comes to fracture prevention, its benefits are minimal. In fact, some say that if taken for more than 10 years, the drug can actually make bones more brittle and increase the risk of fracture.
And stopping the drug is not the answer because Fosamax remains in the body for years after patients stop taking it. Some dentists are even refusing to treat patients who are on this class of drugs, fearful that dental work such as a tooth extraction may bring on a case of ONJ.
Fosamax has been on the market since 1995. Actonel came on the market in 2001 and Boniva arrived last year. As more Fosamax was sold and more bisphosphonates came on the market, more and more injuries showed up. Experts say to just wait and see what happens over the next 10 years.
Fosamax is the world's top-selling bisphosphonate. It is Merck's second best-selling drug, with sales in 2005 of $3.2 billion, according to the Associated Press. In the US alone, more than 22 million prescriptions were written last year, according to the drug research firm IMS Health.
After its launch, Actonel became the fastest product in Proctor & Gamble's history to reach $1 billion in sales.
Boniva was developed by Hoffman-LaRoche, and is co-marketed with GlaxoSmithKline and can be taken once a month while its competitors must be taken weekly.
Novartis's markets Aredia and Zometa, the two intravenous versions used in chemotherapy. Nearly 3 million cancer patients have been treated with intravenous versions of the drugs.
None of these greedy drug makers are going admit that these drugs cause ONJ and throw in the towel as long a $3 billion pot is up for grabs in the US alone. According to Business Week Online, on May 15, 2006, the "global osteoporosis market is at $6 billion in annual sales today, and with a rapidly graying population, it's growing 25% a year."
This class of drugs represents an infinite goldmine for their makers. Advertising to women in their 40s and on up to death, has created a massive market.
"The pharmaceutical industry has every desire that a patient who starts on a bisphosphonate would take it for life," said Dr. Robert Gagel of the MD Anderson Cancer Center in Houston to Gina Kolata of the New York Times. "The bone community, of which I am a member, has always been a bit suspicious of that viewpoint," he noted.
Fighting over this goldmine has got the giant drug makers taking pot-shots at each other. Amgen's osteoporosis drug, Denosumab, is getting ready to come on the market in the next few years, and Amgen is already paving the way to push Fosamax's market share lower.
"At an analyst meeting earlier this year," according to Business Week, Amgen "presented research showing that 70% of patients taking top-selling osteoporosis drugs such as Merck's Fosamax drop out in the first year of treatment because of heartburn, ulcers, and other side effects."
Roger Perlmutter, Amgen's executive vice-president for research and development, pointed out the concerns that Fosamax may cause ONJ.
Perlmutter says that Denosumab mimics the body's natural mechanism for blocking the formation of bone-destroying cells while Fosamax slows down the activity of cells that have already formed.
Amgen's drug, he notes, needs to be taken only twice a year verses once a week for Fosamax.
"What's more, Amgen's drug doesn't bury itself deep in the bone for years the way Fosamax does," Perlmutter told Business Week.
For all those reasons, he said, "we think there would be much less risk of adverse effects."
In the US District Court for the Southern District of New York, Procter & Gamble has asked a judge to force Hoffman-LaRoche to withdraw some of its advertising and stop making some of its claims about Boniva.
P&G alleges that Hoffman has engaged in "an orchestrated, intentional campaign" to tell doctors and consumers that Boniva is just as effective as Actonel and Fosamax, according to a June 2, 2006 article by the Associated Press.
In turn, Hoffman is accusing P&G of falsely telling doctors that they could be sued for malpractice if they prescribed Boniva, and of making efficacy claims not supported by P&G experts, and submitting consumer research with forged signatures to the court.
Merck is also battling to retain its share of the market. On May 13, 2006, Bloomberg News reported that Merck is accusing generic-drug company Teva Pharmaceutical Industries of committing fraud in its successful effort to invalidate Merck's patent on the once-a-week version of Fosamax.
In a lawsuit filed in Delaware, Bloomberg says, Merck is trying to reverse an appeals court decision that threw out its patent on the weekly dose form of Fosamax and wiped out 10 years of potential sales for Merck and opened the door to generic competition when the drug on the main compound expires in February 2008.
Merck has previously failed to get the Federal Circuit to reconsider the decision, and the US Supreme Court has refused to consider the appeal. The new lawsuit cites new evidence that the company claims surfaced in April 2006.
And although Merck is already in the battle of the century defending Vioxx lawsuits, the company is now facing a full frontal attack from Fosamax lawsuits. In April 2006, Linda Secrest filed a lawsuit in federal court in Florida, accusing Merck of failing to warn doctors and patients that Fosamax could hamper blood flow to the jaw.
The lawsuit alleges Secrest began taking Fosamax in 2000, and was diagnosed with jawbone death in 2005 and that the condition is irreversible.
The complaint seeks to represent more than 10 million Fosamax users and the lawsuit is the second of about 200 lawsuits that Secrest's attorney, Tim O'Brien, told Bloomberg News on April 11, 2006, that he plans to file.
Admittedly, Fosamax won't be another Vioxx because Vioxx as a pain killer, was prescribed far more often than Fosamax. But make no mistake, tens of thousands of patients have already been injured over the past decade and the number of lawsuits will be substantial. Experts predict that up to 10% of people who received bisphosphonates may be effected by ONJ.
P&G and Sanofi-Aventis have also been hit with lawsuits but not to the extent of Merck simply because their product was on the market for a much shorter time. Hoffman and GSM have reportedly not been sued over Boniva - yet.
A study cited on April 4, 2006, by United Press International, found more than 2,400 patients who were taking the injected form of bisphosphonate had suffered bone damage to their jaws since 2001, and an additional 120 patients taking the oral form of the drug had been stricken.
Dentists and oral surgeons first began noticing the link between jaw bone death and bisphosphonates 5 years ago, and at first thought that it was only the intravenous versions of the drugs administered to cancer patients that posed a risk. But over the past few years, they discovered that oral bisphosphonates also cause ONJ when taken over a long period of time.
In fact, in March 2006, the American Association of Endodontists issued a position statement recommending that oral surgeons check to see if patients are on bisphosphonates and consider those that are to be at risk for ONJ.
Endodontists specialize in root-canal surgery and warn that "until further information becomes available, the AAE recommends that all patients taking bisphosphonates be considered at some risk."
"While bisphosphonates support the buildup of bone in areas weakened by disease," the group says, "as a side effect of treatment, patients may experience the opposite in their lower and upper jawbones."
The debate over ONJ first gained momentum in 2003 when Dr Robert Marx, chief of oral and maxillofacial surgery at the University of Miami, wrote a paper in the Journal of Oral Maxillofacial Surgery and referred to osteonecrosis of the jaw as "a growing epidemic."
Dr Marx reported 36 patients who had experienced "painful bone exposure," and "were unresponsive to surgical or medical treatments."
The 36 patients had two things in common. They all had cancer and they were all treated with bisphosphonates.
A little over a year ago, on May 13, 2005, Dr Marx told USA Today that he was aware of at least 40 or 50 cases of ONJ nationwide in patients who had taken Fosamax.
Dr Salvatore Ruggiero, chief of oral surgery at the Long Island Jewish Medical Center in New York, quoted in the Wall Street Journal on April 14, 2006, said that of the 155 ONJ cases he had come across, 22 patients were taking Fosamax or another oral bisphosphonate. Some of these patients took Fosamax for seven or eight years, he said.
"With the oral drugs like Fosamax, exposure time is the key," Dr Ruggiero told the WSJ.
Dr Ruggiero says he first saw patients with breast cancer or multiple myeloma who arrived with exposed bone in their mouths. "It looks like a piece of ivory with little tiny holes in it," said he told Gina Kolata of the New York Times on June 2, 2006.
"The one drug they were all on was bisphosphonates," he added.
Dr Ruggiero said he tried scraping away the dead bone and letting it heal, but that only made things worse. "We were creating a larger bone wound that didn't heal," he said.
He told the Times that he called local cancer specialists, but "they said they did not have any experience with this kind of complication."
Attorneys say Merck is going to have a hard time trying to defend Fosamax cases by saying something else caused ONJ, as it has in Vioxx cases, because so few things cause the disease.
In a nutshell, the lawsuits against Merck allege that the company aggressively marketed Fosamax as safe, despite knowing about the potential and dangerous ONJ, without warning doctors and prospective patients about it.
In addition, attorneys say, a jury in a Fosamax case may be swayed by viewing first-hand a disfigured plaintiff suffering from ONJ.