Betty,
Here is that article printed out for ya. If you ever wonder why you ever got into this stock then I suggest you print out this article and pin it up somewhere. If any of your friends ask why you would have bought VIVUS stock 12 months ago when everyone knew about this "miraculous" oral pill that was coming out you can show them the article and save yourself the story:
News You Can Use 1/11/99
HEALTH
Dying for sex
The FDA approved Viagra quickly–perhaps too quickly
BY SHANNON BROWNLEE AND STACEY SCHULTZ
One morning last May, in Visalia, Calif., Mike Howorth woke up at 5:00, intending to surprise his wife. Howorth, who had been suffering bouts of impotence, took a Viagra pill, which he had obtained from his urologist the day before, and went back to bed. Just as the couple was finishing having sex, Howorth, 65, began shaking and passed out. He died two days later of cardiac arrest and brain damage. "I'm very bitter," says his wife, Gerri. "Viagra contributed to my husband's death."
Others have had similar experiences. Since Viagra was approved by the U.S. Food and Drug Administration last March, the agency has confirmed that at least 130 Americans have died after taking the little blue pills, 77 of them from coronary problems such as heart attacks. According to FDA records, hundreds of other men have suffered less deadly but sometimes debilitating side effects after taking Viagra, including strokes, nonfatal heart attacks, and priapism–painful erections that can last hours and cause permanent damage to the penis. At least six men and one widow are suing Pfizer, the manufacturer, claiming the drug caused problems ranging from heart attacks to impaired vision. And the company has beefed up its warnings regarding the drug, cautioning doctors about prescribing it to certain patients.
Viagra is the fastest-selling drug in history and the subject of glowing testimonials as well as ribald jokes. Viagra has also delighted Pfizer stockholders, who have seen share prices jump from $41 in 1997 to $119 in December 1998.
But Viagra's safety record has raised serious questions about whether it was approved too quickly with too little scrutiny, and whether warnings included with the drug gave doctors enough information to prescribe it correctly. "The way in which this drug is being used is recklessly endangering patients," says Sidney Wolfe, director of Public Citizen's Health Research Group, a Washington, D.C., medical industry watchdog.
Pfizer maintains that Viagra is safe when used as directed. "I don't think there is any evidence this drug is dangerous," says Ian Osterloh, who directs Pfizer's clinical trials, the tests on people that determine a drug's safety and efficacy. The number of deaths, says Osterloh, is not unexpected considering that many of the men using Viagra are old and have failing hearts. In fact, he says, Pfizer expected more deaths. It is precisely because Viagra is being used by older, often ailing men, and because it is a sexual aid and not a lifesaving drug, that critics are questioning the speeded-up process that led to its approval. Among their concerns:
Just six months elapsed from the time Pfizer first applied to the FDA for permission to market Viagra until the drug hit pharmacy shelves–too little time for the agency to scrutinize the drug for safety, say outside experts and even some critics inside the FDA. "The agency moved too fast," says one senior FDA official.
The FDA failed to have an independent panel of experts weigh the evidence for or against the drug's approval and help write an appropriate "label"–the fine-print information sheet packaged with drugs to guide doctors in prescribing them. Officially, the FDA says it had no questions about Viagra, so it did not need the panel's advice, but some inside the agency and out believe the decision was shortsighted. Viagra affects blood pressure, says Raymond Woosley, chairman of the pharmacology department at Georgetown University. "It's going to be used in elderly populations. That makes a strong argument for getting feedback from the advisory panel."
Pfizer did not test the drug's safety in patients with serious cardiovascular disease. The drug's original label, however, did not inform doctors about the lack of data on such potential users.
By July 1998, the FDA had received reports of 77 deaths. It took the company and the agency more than four months to agree on a new, more stringent warning label, issued last November.
The FDA's system for monitoring reactions to drugs after release to the market is woefully inadequate, critics say. The FDA estimates that only a fraction of serious drug reactions get reported. This hampers the agency's ability to recall or restrict the use of dangerous drugs. "We don't really know how many men have died or been injured by Viagra. And the FDA and the company are saying don't worry, be happy," says Joe Graedon, a pharmacologist and author of The People's Pharmacy.
What is clear is that Viagra's arrival coincides with a new era of drug regulation. The drug's approval came just as Congress was concluding four years of congressional pressure on the FDA to approve drugs–even lifestyle-enhancing drugs–more quickly. The result has been recalls or restrictions in recent months of half a dozen drugs after their approval, including the heart medication Posicor and the diet pill Redux (chart, Page 64).
Viagra was originally developed to treat angina, or chest pain. Known as sildenafil, the drug works by relaxing blood vessels and increasing blood flow. Tests on heart patients proved disappointing, but Pfizer researchers noticed an intriguing side effect: The dilated blood vessels helped men get erections. That side effect would turn out to be good news for Pfizer. In 1994, the Journal of Urology reported that as many as 30 million American men were impotent–an enormous market with few effective remedies available.
Stock shock. The company went to full-scale clinical trials, using sildenafil to treat impotence in more than 3,000 men. The researchers were careful to exclude men with serious heart conditions or high blood pressure, or those who had had a stroke or heart attack in the past six months. Public Citizen's Wolfe and other critics charge that Pfizer kept such men out of its trials because they knew the drug could affect their hearts. "There's no question they excluded these patients for safety worries," says Wolfe. But Pfizer's Osterloh says safety was not the issue. He says they excluded such men from trials because "we thought they wouldn't be thinking about sex" and their numerous medications might interact with Viagra, making it difficult to determine if the drug worked.
When news of the trials reached Wall Street, Pfizer stock jumped 66 percent between January and October 1997. And would-be Lotharios flooded phone lines calling their doctors. "I had a list of 250 men who wanted me to call them the minute it was approved," says Ronald Lewis, chief of urology at Georgia Medical College. Wall Street analysts projected sales of up to $11 billion a year.
Congress, meanwhile, was debating reauthorization of PDUFA, or the Prescription Drug User Fee Act (known as "pahDOOfah"). The law requires drug companies to pay fees to the FDA so it can hire more people to review new drug applications. First passed in 1992, PDUFA brought many more drugs to market by slashing the average time for review and approval to just a year. By 1997, Congress was also moving ahead with the FDA Modernization Act, or FDAMA. Among its provisions were ones whose origins lay in the idea of speedy approval of lifesaving drugs. But FDAMA hastened approval of many types of drugs, not just those treating deadly illnesses. At the same time, FDAMA set no funds aside for the agency's drug safety divisions. The cowed regulatory agency began talking about forging a "partnership" with drug companies to bring more drugs to market faster.
Campaign donations. During the PDUFA and FDAMA hearings, pharmaceutical industry money poured into congressional campaign coffers–$8.3 million in 1997 and the first nine months of 1998. Pfizer was always generous. Its PAC gave $288,050 during those two years. In the category of soft money, Pfizer spent $609,550, making it the biggest giver among pharmaceutical companies, Federal Election Commission records show.
On Sept. 29, 1997, as FDAMA was moving forward in Congress, Pfizer delivered several boxes of clinical data to the FDA. In the midst of combing through all the data, the FDA also had to decide whether to refer Viagra's application to an advisory panel of heart and renal experts. Such panels of outsiders are often asked by the FDA to help determine whether a drug should be marketed and what warnings should accompany it. Indeed, a cardio-renal committee was scheduled to meet in January 1998. But on November 25, the FDA decided not to consult them. Viagra's principal FDA reviewer, Norman Stockbridge, says he felt that Pfizer had provided excellent data, had done its studies very carefully, and had demonstrated the drug's effectiveness and safety. "There were no issues on which we thought we needed [the committee's] help," he says.
Most members of the committee agree with Stockbridge. But not all. Says Lemuel Moye, a statistician at the University of Texas and a member of the advisory committee: "It's the first time such a drug has been approved, and I'm surprised [we didn't see the application]."
On March 27, Viagra got FDA approval. Its original label warned against giving Viagra to men who were also on nitrates, drugs used to control angina and high blood pressure. Viagra and nitrates in combination could cause a dangerous drop in blood pressure. The label also stated that "there is a degree of cardiac risk associated with sexual activity" and that doctors might want to check the heart health of their patients. But there was no mention of the fact that Pfizer did not know if the drug was safe for men who had severe heart disease or who had recently had heart attacks or strokes. Pfizer says such a lack of data is not normally included in a label. Critics question whether the advisory committee, if it had seen Viagra data, might have forced a more stringent warning, alerting doctors that they should use caution when prescribing the drug.
Within the first month after Viagra's launch, 598,000 prescriptions were written, far outpacing popular big-sellers like Prozac. The end of 1998 saw nearly 6 million prescriptions worth more than $441 million. Sales were boosted by doctors quoted in the national media, pronouncing the drug "very safe." Statements like this and the lack of warnings in the label led many men and their doctors to consider Viagra quite safe. One prominent Washington, D.C., urologist, who does not want his name used, confesses that at first he didn't consider possible cardiac effects.
Easy access. Viagra is also easy to get. It can be obtained over the Internet (box, this page). "We've had pediatricians in our community writing prescriptions for neighbors. These deaths have been the bitter harvest from that kind of behavior," says William Steers, chairman of urology at the University of Virginia.
Some men even lie to get the drug. Georgia Medical College's Lewis says he prescribed Viagra to a man who swore up and down that he wasn't on nitrates. Then, in a chance meeting with the man's regular physician, Lewis learned that the man was in fact on the drugs. "You can't imagine the patients who are asking for Viagra," says Franz Messerli, cardiologist and former member of an FDA advisory committee. "They have had multiple heart attacks. I have warned patients time and again, and nevertheless they get Viagra."
The first death reported to the FDA occurred on April 28, a month after Viagra was launched. A little more than a week later, a 62-year-old man who had taken the drug went into cardiac arrest.
On July 1, Public Citizen petitioned the FDA, urging that Viagra's warning label be stiffened. By then, the FDA had received reports of 77 deaths, and stories had begun to appear in the news media, warning of possible dangers.
Both the FDA and Pfizer say there is no evidence the deaths were caused by Viagra itself. In a July 1 Associated Press story, company spokeswoman Mariann Caprino said, "There are no new trends that have emerged that would warrant a change in the product's label." But by then, the FDA had already told Pfizer that there would have to be a new label. Those relabeling talks took more than four months–a time period the FDA says is not unusual for making changes in labels. Some FDA insiders say the process was slow because the agency and the company sparred over the wording of the label. Company spokesman Andy McCormick says, "It's a discussion of data, and it takes time. We were making our case responsibly."
The new label now carries stronger warnings. It informs doctors that patients with severe cardiac problems were not tested, so the drug's safety in that group isn't known. The label also highlights warnings that sex can be risky for cardiac patients. Moreover, a "Dear Doctor" letter sent by Pfizer last month to 150,000 physicians contains more urgent warnings, telling doctors that "serious cardiovascular events . . . have been reported in association with the use of Viagra." The letter points out that some of the incidents "were reported to occur shortly after the use of Viagra without sexual activity."
Still unanswered is why men have died after taking Viagra. Out of the 130 deaths confirmed by November 1998, 16 occurred when the men were also taking nitrates, drugs that were explicitly warned against in both labels. But nitrates can't explain the 114 other deaths. Pfizer maintains that Viagra is not the problem–it's the sex. Indeed, the reason Pfizer expected more deaths is that sex can tax an ailing heart, says Pfizer's Osterloh, and the average consumer of the drug was already at risk for heart attacks.
As a result, Pfizer and FDA officials have suggested that deaths were predictable from the health statistics of Viagra's 6 million users. But other impotence remedies have lower reported death rates. MUSE, for example, made by California-based Vivus, requires that a man insert a small tablet of the drug alprostadil into the urethra. About 50 percent of users get an erection. Vivus has sold 1.2 million prescriptions of MUSE, with only a single death reported worldwide. If Vivus had 6 million users, like Viagra, five deaths would be expected, according to a Vivus official. Pfizer argues that with all the publicity surrounding Viagra, deaths from it are more likely to be reported than deaths from other drugs like MUSE. (The FDA last month asked Pfizer's CEO to come in to discuss the company's "delays and failure to provide information" on other drugs. Pfizer says the company will meet with the FDA but does not know what the agency is referring to.)
The truth is, no one knows how many deaths have been associated with impotence remedies. The FDA estimates between 1 percent and 10 percent of adverse reactions are reported. That means the number of deaths associated with Viagra could be 130, or it could be 1,300. The uncertainty lies with the haphazard system that tracks a drug's side effects once it has gone to market. While drug companies are required to inform the agency of adverse effects they hear about, most don't actively monitor the safety of their products once the cash register starts ringing. Doctors don't always know what drugs patients have taken when they die, and there are no laws telling physicians to report drugs' side effects to the FDA.
Guinea pigs. This poses a danger for patients taking new medications. Drugs are studied in clinical trials involving a defined set of patients and excluding all others, and it is often not until a drug is being used by the public at large that potentially deadly side effects can emerge. Some critics of the system say that releasing a drug on the market amounts to a giant uncontrolled experiment in which the first million users are essentially guinea pigs.
The solution, some argue, is an independent board charged with monitoring drug safety, much like the National Transportation Safety Board. That seems unlikely. Drug companies lobbied Congress hard against beefing up post-marketing surveillance at the FDA during debates over FDAMA. And the Senate labor committee has scolded FDA Commissioner Jane Henney for authorizing an internal safety review board.
Without definitive data from a post-market surveillance system, doctors say potential Viagra users should exercise caution. Before prescribing Viagra, Georgia Medical College's Lewis says he asks patients at risk an important question: "Is sex worth dying for?"
With Sheila Kaplan, Gary Cohen, Penny Loeb, and Susan Brink
Withdrawal symptoms
Several companies have withdrawn drugs from the market in the past 16 months after side effects proved too dangerous:
NAME OF DRUGS: Redux and Pondimin
TREATMENT FOR: obesity
PROBLEM CAUSED: heart valve abnormalities when used in combination with phentermine
DATE WITHDRAWN: September 1997
NAME OF DRUG: Seldane
TREATMENT FOR: allergies
PROBLEM CAUSED: serious heart problems when combined with certain drugs
DATE WITHDRAWN: February 1998
NAME OF DRUG: Duract
TREATMENT FOR: pain
PROBLEM CAUSED: liver failure when taken for extended periods of time
DATE WITHDRAWN: June 1998
NAME OF DRUG: Posicor
TREATMENT FOR: heart disease
PROBLEM CAUSED: harmful interactions with any of 25 other drugs
DATE WITHDRAWN: June 1998
DRUG DEALS
Buying Viagra on the Internet
"Need Viagra?" . . . "No prescription?". . . "No problem." The pitches popped up immediately when U.S. News typed "buy Viagra" into Internet search engines. Eight World Wide Web sites were found that offered to sell Viagra and ship it within 48 hours.
An applicant typically agrees to pay a "consulting fee," fills out a health questionnaire that asks about medical condition and medication taken, pledges that he is familiar with Viagra's risks, and supplies a credit card number. If approved, the applicant is charged $75 for the consultation, and the Viagra arrives in short order. The charge is $6 to $10 a pill; one Web site offered up to 300 pills.
Quick approval. A U.S. News staffer applied, disclosing that he had had two open-heart surgeries, one in 1983 and one in 1998. He was quickly approved, and his Viagra was shipped. The staffer reached the prescribing doctor, who said that he was aware of reports that 16 people on nitrates had died after taking Viagra, but that since the staffer was not on nitrates, he saw no reason not to prescribe Viagra for him. He said he did not believe news reports of 130 Viagra-associated deaths. The doctor said he was not troubled by prescribing to a patient he did not know without calling the patient, obtaining his chart, or consulting his regular physician. "If you go to a doctor, how does he know you're telling the truth? If you lie about a heart condition, how does he know? Before I approve a prescription, I look at your form, your records. If you're not comfortable with this, you should go to a doctor," he said.
Adolph Hutter, a cardiologist at Massachusetts General Hospital, calls buying Viagra on the Web "dangerous." "Anybody who needs to use Viagara obviously has some medical problems," he says, "and should check with their doctor as to whether it's safe and appropriate."–Gary Cohen
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