News: March 2005

No Viagra recall yet despite eye stroke cases

Update

Since the publication of this article, more news have come out regarding a likely recall of Viagra. We are closely following this story and a list of all news stories related to Viagra is available at Viagra recall news page.

Previous story
As they say, every drug has pluses and minuses. We saw that after Vioxx recall was announced that a drug that seemed to be excellent for pain relief actually killed tens of thousands of Americans. Now Viagra is being examined by scientists for possible side effects related to vision.

Ophthalmologists at the University of Minnesota say in an article published in the Journal of Neuro-ophthalmology that a condition that causes permanent vision loss has been diagnosed in a small group of men who have taken the erectile dysfunction drug Viagra. The condition, nonarteritic ischemic optic neuropathy (NAION), described as “stroke of the eye,” occurs when blood flow is cut off to the optic nerve, which injures the nerve and results in permanent vision loss.

Seven patients, aged between 50 and 69 years, had typical features of NAION within 36 hours after ingestion of Viagra for erectile dysfunction. Seven similar cases have been previously reported. Pfizer, the maker of Viagra, has not commented on the research and merely says on its website, "...that Less common (side effects) are bluish or blurred vision, or being sensitive to light. These may occur for a short time."

“For years, we’ve known that some men who take Viagra will experience temporary color changes in their vision and see things as blue or green,” said Howard Pomeranz, M.D., associate professor of ophthalmology at the University of Minnesota Medical School. “NAION is a much more serious condition because it can lead to permanent vision loss.”

All of the patients had at least one arteriosclerotic risk factor, including hypertension, diabetes, hypercholesterolemia, or hyperlipidemia. All of the patients also had a low cup to disk ratio, which is a way doctors measure the small circular indentation where the optic nerve connects to the eyeball. The low cup to disk ratio means that the blood vessels and nerves are tightly bundled together into the small space in the back of the eye.

“Viagra regulates a chemical in the body to constrict the arteries. This constriction may cut off the blood flow to the optic nerve, especially in people with a low cup to disk ratio, where the blood vessels and nerves are tightly bundled provoking NAION,” says Pomeranz.

The onset of NAION within hours after ingestion of Viagra in 14 patients supports an association between the use of the drug and NAION. Based on the fact that 14 cases of NAION have now been reported soon after the use of Viagra, the researchers believe that ophthalmologists should ask all men with NAION about the use of Viagra, and recommend that patients with a history of NAION in one eye be cautioned that Viagra may increase the risk of NAION in the fellow eye.

Useful links
Journal of Neuro-ophthalmology
University of Minnesota
University of Minnesota Medical School
Pfizer
Viagra

Abbott Laboratories announces Cylert recall

It is extremely sad that in the United States the work of FDA has to be done by consumer rights groups. It is no longer a secret that the FDA has failed completely in its mission to protect the lives of American people by ensuring drug safety. Not only are drugs approved without adequate research, once they are approved, FDA does nothing to recall dangerous drugs that are on the market. Vioxx recall has received the most coverage during recent months but there are numerous other drugs that Americans should not be using but they continue to be on the market.

That is why the news of Cylert recall by Abbott Laboratories is an excellent example. Over a period of 30 years, Cylert (or pemoline), has been criticized for its dangerous side effects, but in its usual style to keep the pharma companies happy, FDA left the drug on the market.

On March 24, Public Citizen, a consumer rights group, prepared an excellent case in favor of Cylert recall and submitted it to the FDA. The very next day, Cylert manufacturer Abbott Laboratories announced that it is pulling the drug off the market, citing one of those reasons that you know is not accurate ("declining sales"). If sales were so low, why risk the lives of Americans all these years? And why recall Cylert the very next day after a petition by Public Citizen? Or was there a sneaky phone call from FDA to Cylert to act fast?

In any case, the good news is that Cylert is off the market. But what about other ADHD drugs like Prozac, Ritalin, and Adderall? As usual, FDA is doing nothing hoping that Americans will stop paying attention soon.

Recommended article: Natrecor recall not yet announced

Cylert recall demanded over safety concerns

After Adderall XR recall in Canada, and the refusal of the FDA to take similar action in the US, a lot of concern has been raised about other attention deficit hyperactivity disorder (ADHD) drugs like Prozac, Ritalin, Cylert, etc. Now Public Citizen, representing more than 150,000 consumers nationwide, is petitioning the FDA to recall pemoline (sold as CYLERT, made by Abbott Laboratories, and all its generic versions).

Several doctors, including Dr. Sidney Wolfe, who have written to the FDA, say that, "In addition to having no demonstrated unique therapeutic benefit over other ADHD drugs such as methylphenidate, pemoline is known to have caused at least 21 cases of liver failure, including 13 resulting in liver transplantation or death. The drug's unfavorable risk to benefit ratio has led to its withdrawal in the United Kingdom and Canada, while the FDA instead opted for two separate changes to the pemoline label, in 1996 and 1999. A 2002 FDA study has clearly demonstrated that these labeling changes failed to increase monitoring for liver toxicity or ensure only second-line use of pemoline. In light of this evidence of unique liver toxicity without evidence of unique therapeutic benefit, we contend that the only responsible course of action is to remove this dangerous drug from the market."

Pemoline, a central nervous system stimulant, was approved by the FDA for the treatment of ADHD on January 27, 1975. There were always concerns about its safety. A black box warning was added to the labeling for pemoline in the United States in December 1996, and a "Dear Doctor" letter was mailed out from Abbott to all U.S. physicians. The warning stressed pemoline's liver toxicity and recommended that it should no longer be considered a first-line therapy for ADHD. This decision to make pemoline a second-line therapy was made without any clinical trials showing that it actually worked in patients who had failed to respond to a first-line therapy. As liver failure cases continued to accumulate, the FDA addressed the issue with a stronger black box warning in June 1999. The 1999 warning label states that as of December 1998 there were 15 cases of acute liver failure due to pemoline reported to the FDA, 12 of which resulted in death or liver transplantation.

While the United States has allowed Abbott to continue marketing the drug, other countries have taken more decisive action based on patient liver toxicity data collected predominantly from the U.S. In September 1997, the United Kingdom removed pemoline from the market. The UK decision was based entirely on case reports of liver toxicity from the United States. In September 1999, the Canadian government reached a similar conclusion and removed pemoline from the market, reasoning that the drug's risks outweighed its benefits. (Related article: FDA reportedly pressured Health Canada not to recall Adderall XR)

In its usual attitude favoring drug companies over the health of American people, the FDA has not taken any decisive action so far and it is unlikely that much will happen this time either. A Crestor recall request was recently denied by the FDA, even though similar safety concerns remain.

Recommended articles

Shire expects that Health Canada will reverse its Adderall XR recall decision

American doctors support FDA decision on Adderall

Adderall XR to stay on the market in the US

Tysabri and Avonex combination had no benefits

John Strahinich and Brett Arends of Boston Herald are reporting that Biogen, the maker of now recalled multiple sclerosis drug Tysabri and Avonex (which has been linked to liver damage though it has not been recalled yet), may have pushed a combination of Tysabri and Avonex even though there is no study that shows that the combination is better than Tysabri alone. (Related article: Tysabri recall)

The authors rely on an interview with neurologist Patricia Coyle of State University of New York at Stony Brook. Two other doctors - Dr. Barry Singer, an MS expert at the Washington University School of Medicine in St. Louis, and Dr. Ugo Goetzl, who runs the Millennium Clinic in Durham, NC, also spoke to Boston Herald and agreed with Dr. Coyle's assessment.

And it is understandable why Biogen would do it. Tysabri costs approximately $30,000 a year based on pre-recall prices and Avonex costs half of that. A combination creates 50% more revenues for the firm. It may be recalled that Biogen executives engaged in insider trading just before Tysabri was recalled. One executive, Thomas Bucknum, Executive Vice President and General Counsel, has already resigned and investigations by regulatory agencies are continuing.

Related articles

Marketing of Tysabri suspended

Tysabri class action lawsuit

Second Tysabri patient confirmed with PML

Source: BostonHerald

Natrecor damages kidney, no recall yet

According to an article published in the medical journal Circulation, Natrecor (nesiritide), made by Johnson & Johnson (Scios Inc.), caused a 40 percent to 50 percent greater risk of reduced kidney function when compared with more conventional therapies for heart patients. Natrecor is used to treat patients with congestive heart failure who have shortness of breath at rest or with a small amount of activity.

Over 5 million people in the United States have congestive heart failure. Each year, there are an estimated 400,000 new cases, and half of those diagnosed with the condition will be dead within five years. Natrecor (nesiritide) Injection, a synthetic version of a human hormone, works by dilating the veins and arteries so more blood can flow through them. Decompensated heart failure results in nearly one million hospitalizations annually, the most common reason for hospitalization among people over age 65.

The FDA approved the drug in 2001 and had a rather simple warning that patients need to tell their doctor about their kidney problems. The most common side effect with Natrecor is low blood pressure, the FDA says. FDA based its approval on scientific data from a number of controlled clinical trials in people with acute CHF, including the Vasodilatation in the Management of Acute Congestive Heart Failure Trial (the VMAC study). The VMAC study involved a total of 489 patients who required hospitalization for the management of shortness of breath at rest due to CHF. VMAC participants were randomized and treated with Natrecor, intravenous nitroglycerin or placebo (for 3 hours). In the VMAC study, patients receiving Natrecor reported greater improvement in shortness of breath than patients receiving placebo.
The company says that Natrecor may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with the drug may be associated with azotemia.
European Medicines Agency (EMEA) has not yet approved Natrecor.

"Nesiritide was associated with a 40 to 50 percent higher risk of worsening kidney function when used for the treatment of acutely decompensated heart failure," reported Jonathan Sackner-Bernstein, MD, the study's principal investigator and director of clinical research at the Heart Failure and Cardiomyopathy Center at North Shore University Hospital in Manhasset, NY. "This data is based on analysis of the randomized, controlled trials conducted by Scios, which studied the effects of Nesiritide in over 1,200 patients. Whether using low or high doses, Nesiritide was associated with significant risk of kidney dysfunction."

"We're all looking for ways to get our heart failure patients feeling better and discharged from the hospital as quickly as possible," said Keith Aaronson, MD, associate professor in the Division of Cardiovascular Medicine at the University of Michigan, and a co-investigator of the Circulation study. "Nearly all of these hospitalizations occur because patients are short of breath from retaining too much fluid. Many physicians have embraced nesiritide in the belief that fluid can be removed and symptoms improved more quickly without risk. According to the data, that just isn't so."

"As of yet, we do not understand how Nesiritide leads to worsening kidney function in patients with decompensated heart failure. But we do know that worsening kidney function is troubling, in that it generally is associated with a higher risk of death. Together, these observations suggest the need for appropriately sized clinical trials to establish the safety of nesiritide relative to its benefits on symptoms," said Dr. Sackner-Bernstein.

Celebrex has anti-cancer properties

Celecoxib, a selective COX-2 inhibitor with promising anti-cancer properties, has now been found to attack prostate cancer cells in a second way that differs from Vioxx (rofecoxib), another anti-inflammatory drug that also inhibits COX-2.

In studies published in the March 1 issue of the journal Clinical Cancer Research, scientists at the Weill Medical College of Cornell University revealed that celecoxib, marketed under the name Celebrex by Pfizer, not only targets COX-2, but also reduces levels of a key protein, cyclin D1, thats critical for cell replication.

"It is well established that COX-2 is a significant and rational target for anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer prevention at the Weill Medical College of Cornell University and senior author of the paper. "These studies suggest that celecoxib exerts a second mode of action independent of its known anti-inflammatory mechanism that imposes further restrictions on the proliferation of prostate cancer cells. The results provide potentially important insights into our understanding of the overall anti-tumor activity of selective COX-2 inhibitors."

It may be noted that Celebrex has been under a lot of spotlight lately after it was found that it increased the risks of cardiovascular events, similar to other drugs in the same class, Vioxx and Bextra. While Vioxx was recalled in September 2004 and there were repeated calls for Celebrex recall as well, but in a bizarre turn of events, a FDA panel filled with many members with ties to Merck and Pfizer, recommended that Celebrex be allowed to stay on the market.

Dannenberg and a team of investigators discovered this new mechanism by applying celecoxib to prostate cancer cells that failed to express COX-2. Here, the scientists observed that the celecoxib-treated cancer cells did not replicate as rapidly as untreated cells. After further analysis, they found the drug worked by suppressing amounts of cyclin D1, a protein that's essential if cells are to grow, divide and spread.

The scientists also attempted to replicate the experiment with Vioxx substituting for celecoxib. In this case, the prostate cancer cells continued to flourish. "These results support the notion of a unique action by celecoxib that is independent of COX-2, and that's different from Vioxx," said Dannenberg. "These beneficial effects were observed at concentrations of celecoxib that occur in humans," added Dannenberg. "This increases the likelihood that our findings are clinically relevant."

Dannenberg and his colleagues then demonstrated that celecoxib worked in animals that served as hosts for human prostate tumors. In this animal model, celecoxib not only was shown to reduce proliferation of cancer cells, but also reduced the growth of blood vessels at the tumor sites. As a result, tumor mass and blood vessel density in the treated animals was about half that observed in the untreated animals.

Contributing to the studies, along with Dannenberg, were Kotha Subbaramaiah, Baoheng Du and Mindy Chang from Weill Medical College of Cornell University, New York, N.Y.; Manish Patel, Carlos Cardon-Cardo, and Howard Thaler, Memorial Sloan-Kettering Cancer Center, New York, N.Y.; and Peiying Yang and Robert Newman, UT M.D. Anderson Cancer Center, Houston, Texas. This research was supported by funding from the National Cancer Institute.

Links

AACR

WMC

Ritalin may damage DNA and cause cancer

Health Canada, the drug regulatory agency in the country, recalled Adderall on concerns that it may have caused death in children. Contrary to Health Canada's interpretation of the data, the US Food & Drug Administration (FDA), which typically favors drug companies rather than worry about the health and lives of Americans, not only decided to leave the Adderall on the market, it actually tried to stop Health Canada from suspending sales in Canada, according to Senator Charles Grassley.

Bloomberg is reporting that Ritalin, another drug in the same class as Adderall, may cause damage to DNA that can raise cancer risk in children. While the study is small and preliminary, it does raise concerns about prescribing Ritalin to children. Ritalin is the most widely prescribed drug for treating attention deficit/hyperactivity disorder. Six million to 10 million Americans, many of them children, take it. Ritalin is made by Novartis. Other drug in the same category, apart from Adderall XR, is Concerta by Johnson & Johnson.

The team of researchers was led by Randa El-Zein of the University of Texas M.D. Anderson Cancer Center in Houston.

Avonex linked to liver damage; no recall yet

FDA and Biogen have made an important update to the prescribing information for AVONEX (Interferon beta-1a) without doing a press release or highlighting it prominently on their websites. On the FDA's website, the information is buried in one of those hard-to-find corners. A press release could not be found on Biogen, the Avonex manufacture, website. AVONEX, a multiple sclerosis (MS) drug was introduced to the market in 1996. In another related development, GlaxoSmithKline said that the FDA has ordered a halt to the trial of its own MS drug, that works similar to Tysabri. (Related article: Tysabri recall)

In the revised letter to the doctors, it is indicated that post-marketing experience from Avonex shows severe hepatic injury, including cases of hepatic failure, in patients taking AVONEX. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential for hepatic injury should be considered, the revised letter advises, when AVONEX is used in combination with other products associated with hepatic injury, or when new agents are added to the regimen of patients already on AVONEX.

Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with AVONEX. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of AVONEX used in combination with known hepatotoxic drugs or other products (e.g. alcohol) should be considered prior to AVONEX administration, or when adding new agents to the regimen of patients already on AVONEX. Patients should be constantly monitored for signs of hepatic injury.

Biogen has been in deep trouble since Tysabri recall and its executives are being investigated for insider trading just before the news about Tysabri was made public.

FDA criticizes misleading Crestor ads; refuses recall

The U.S. Food and Drug Administration’s (FDA) has refused the request of a consumer rights group to recall Crestor. Readers might recall that world-famous FDA scientist Dr. David Graham has put Crestor in the same category as Vioxx - drugs that are simply too dangerous to be on the market since the FDA does not fully understand their risks.

Crestor is a member of a class of cholesterol-lowering drugs commonly referred to as 'statins' and was approved in the U.S. in August 2003. Earlier this month FDA issued only a health advisory against Crestor to re-emphasize recommendations made in the original label about the need for physicians to consider using lower starting doses of the drug in some individuals as a means of reducing the risk of rhabdomyolysis (serious muscle damage). The drug is particularly dangerous for people of Asian origin.

Last week, FDA also warned the Crestor manufacturer AstraZeneca to immediately cease misleading advertisements for Crestor charging that a TV ad and the “STELLAR” print ads make false or misleading claims regarding the superiority of Crestor. The agency says that Crestor's "comparison with Lipitor is misleading because it suggests that Crestor is superior to Lipitor when in fact none of the approved doses of Crestor was significantly superior to 80 mg of Lipitor in the STELLAR study."

Sidney Wolfe, Director of Public Citizen’s Health Research Group criticized FDA's action saying that the agency has once again sided with the drug industry rather than the American people. Senator Chuck Grassley who is working to shake up the agency has accused Merck of manipulating FDA in the Vioxx case since FDA at no point tried to make American people aware of the dangers of Vioxx. Dr. Wolfe in a statement says that "This response should give no comfort to either physicians or patients who are using or considering using Crestor." He mentions Baycol, Rezulin, and Vioxx as examples of drugs that FDA knew were dangerous but left them on the market to keep the drugmakers pleased. In a recent case, FDA refused to recall Adderall and even tried to pressure Health Canada not to do so. Adderall is still available in the United States. (Related article: FDA must recall Adderall till sufficient safety data is available)

Dr. Wolfe is expecting that science will eventually show that Crestor is indeed a drug that is not safe. "Once again, when faced with concerns about the safety of a drug, the FDA has sided with the drug company, AstraZeneca, instead of the public. When Crestor is taken off the market, if not before, this will represent yet another blow to the agency’s badly tarnished reputation," he says.

Recommended article: FDA hijacked by the drug industry

Cough syrup recall in Canada due to safety concerns

Health Canada, the drug regulatory agency in Canda, is advising consumers across Canada not to use specific brands of "Cough Syrup DM" DIN 02015781 with lot numbers starting with 2J29 and 3J29 due to the product containing twice the amount of dextromethorphan than is stated on the label.

At the request of Health Canada, this product is being recalled by the manufacturer, Jamp Pharmaceutical Corp in Langley, British Columbia. The "Cough Syrup DM" is packaged in 100mL and 250mL plastic bottles. The product is distributed to retailers across Canada and sold under the following brand names:

People First
PharmaChoice
Procurity Encounter
ARP Preferred
Medicine Centre
United Pharmacy
Western Family

Consumption of this product may result in light-headedness, fatigue and slurred speech. Children under the age of three may be more vulnerable to possible adverse effects, including seizures, from this product.

People should return this product to the pharmacy. Individuals who are concerned about their health after consuming this product are advised to seek medical assistance.

Eczema drug Protopic may cause cancer

The US Food and Drug Administration (FDA) today advised health care professionals to prescribe Protopic (tacrolimus) only as directed and only after other eczema treatments have failed to work because of a potential cancer risk associated with their use. In addition, FDA is adding a black box warning to the health professional label for Protopic and developing a Medication Guide for patients. Protopic was approved in 2000. Similar action is also being taken against another drug Elidel.

Today’s actions follow the recommendations made by the FDA’s Pediatric Advisory Committee during its February 15, 2005 meeting. At this meeting, findings of cancer in three different animal species were reviewed. The data showed that the risk of cancer increased as the amount of the drug given increased. The data also included a small number of reports of cancers in children and adults treated with Protopic.

The manufacturers of Protopic, Fujisawa Healthcare, has agreed to conduct research to determine whether there is an actual risk of cancer in humans, and, if so, its extent. No recall of Protopic is being mentioned at this time either by the FDA or Fujisawa Healthcare. Protopic is applied to the skin to control eczema by suppressing the immune system. FDA’s Public Health Advisory specifically advises physicians to weigh the risks and benefits of Protopic in adults and children and consider the following:

Protopic is approved for short-term and intermittent treatment of atopic dermatitis (eczema) in patients unresponsive to, or intolerant of other treatments.
Protopic is not approved for use in children younger than 2 years old. The long-term effect of Protopic on the developing immune system in infants and children is not known.
Protopic should be used only for short periods of time, not continuously. The long term safety of these products is unknown.
Children and adults with a weakened or compromised immune system should not use Protopic.
Use the minimum amount of Protopic needed to control the patient’s symptoms. The animal data suggest that the risk of cancer increases with increased exposure to Protopic.

Useful links

FDA

Protopic

Fujisawa Healthcare

Eczema drug Elidel may cause cancer

The Food and Drug Administration (FDA) today advised health care professionals to prescribe Elidel (pimecrolimus) only as directed and only after other eczema treatments have failed to work because of a potential cancer risk associated with their use. In addition, FDA is adding a black box warning to the health professional label for the drug and developing a Medication Guide for patients. Elidel was approved in 2001 to treat eczema. Elidel cream and Protopic ointment are topical immunosuppressant calcineurin inhibitors that are applied to the skin and are the only approved drug products in this class. At this time, there is no mention of a recall of Elidel either by the FDA or Novartis. Protopic, another eczema drug, is also receiving a similar black box warning.

This FDA action follows the recommendations made by the FDA’s Pediatric Advisory Committee during its February 15, 2005 meeting. At this meeting, findings of cancer in three different animal species were reviewed. The data showed that the risk of cancer increased as the amount of the drug given increased. The data also included a small number of reports of cancers in children and adults treated with Elidel.

The manufacturer of Elidel, Novartis, has agreed to conduct research to determine whether there is an actual risk of cancer in humans, and, if so, its extent. Elidel is applied to the skin to control eczema by suppressing the immune system. FDA’s Public Health Advisory specifically advises physicians to weigh the risks and benefits of these drugs in adults and children and consider the following:

Elidel is approved for short-term and intermittent treatment of atopic dermatitis (eczema) in patients unresponsive to, or intolerant of other treatments.
Elidel is not approved for use in children younger than 2 years old. The long-term effect of Elidel on the developing immune system in infants and children is not known. In clinical trials, infants and children younger than 2 years of age treated with Elidel had a higher rate of upper respiratory infections than those treated with placebo cream.
Elidel should be used only for short periods of time, not continuously. The long term safety of these products is unknown.
Children and adults with a weakened or compromised immune system should not use Elidel.
Use the minimum amount of Elidel needed to control the patient’s symptoms. The animal data suggest that the risk of cancer increases with increased exposure to Elidel.

Useful links

FDA

Novartis

Elidel

Biogen executive quits after Tysabri recall

Wouldn't you think that all these executives who get powerful jobs and make a ton of money know that insider trading is illegal? May be they don't but they probably still noticed that Martha Stewart went to jail for insider trading. Our hypothesis is that these folks knowingly commit illegal acts with the hope that they will never be caught. Does it also mean that every single day thousands of senior executives in American corporations are committing illegal acts like insider trading and getting away with it because they never get caught?

May be that is exactly what our dear friend Thomas Bucknum, Executive Vice President and General Counsel at Biogen was thinking. The day Tysabri recall was being announced, the guy was busy selling Biogen stock. Don't you wonder what was he thinking? In an announcement, the company gave no reason for the departure. Actually, there is no mention of insider trading by him at all, and interestingly enough, neither is one of those "I want to spend more time with my family" reasons that we all know how hollow they are.

It may be noted that Tysabri is a drug for multiple sclerosis and the drug received approval using the infamous fast-track process at the FDA. Many other drugs that received fast track approvals, for instance Vioxx, are all mired in controversy due to the use of a faulty process that is exploited by the drug industry. After problems were reported with the drug, Biogen decided to recall Tysabri though there is speculation that the drug may return later.

So what is the outcome? The poor shareholders get hurt and it develops a sense of distrust in the minds of the investors. The more such things happen the more suspicious we are of statements made by American corporations. No surprise then that investors have no choice but to file class action lawsuits against Biogen.

Class action lawsuit filed against Biogen in Tysabri recall case

Tysabri recall by Biogen Idec, particularly the news that some executives may have also engaged in insider trading, has sparked a lot of controversy. The law firm of Schatz & Nobel, P.C., has announced that a lawsuit seeking class action status has been filed in the United States District Court for the District of Massachusetts on behalf of all persons who purchased the publicly traded securities of Biogen Idec Inc. ("Biogen") between February 18, 2004 and February 25, 2005.

The Complaint alleges that Biogen violated federal securities laws by issuing false or misleading information. Specifically, defendants failed to disclose and misrepresented the following material adverse facts:

That TYSABRI (natalizumab), a monoclonal antibody for the treatment of Multiple Sclerosis ("MS"), posed serious immune-system side effects;
That TYSABRI, like other MS drugs, made patients susceptible to progressive multifocal leukoencephalopathy ("PML") by changing the way certain white blood cells function, thereby allowing PML, a normally dormant virus, to run rampant within the human body;
That defendants knew and/or recklessly disregarded documented facts that MS drugs can cause greater incidents of PML to occur; and
That defendants concealed these facts in order to fast track TYSABRI for FDA approval so that they could reap the financial benefits from the sales of the drug.

On February 28, 2005, before the market opened, Biogen announced a voluntary suspension in the marketing of TYSABRI because of two serious adverse events that have occurred in patients treated with TYSABRI in combination with AVONEX (Interferon beta-1a) in clinical trials. On this news, shares of Biogen fell $28.63 per share, or 42.44%, to close at $38.65 per share. On March 4, the second patient was also confirmed as having contracted PML.

Related article: FDA advisory on Tysabri

Paxil CR recall and seizure hurt patients

In a response to ongoing concerns about manufacturing quality at plants of GlaxoSmithKline, Inc. (GSK), the Food and Drug Administration (FDA) and the Department of Justice today initiated seizures of Paxil CR. Manufacturing practices for Paxil CR, approved to treat depression and panic disorder, failed to meet the standards laid out by FDA that ensure product safety, strength, quality and purity. The FDA action relates to all strengths of Paxil CR (12.5 mg, 25 mg, and 37.5 mg).

"FDA and the Department of Justice will not allow drug manufacturers to ignore our high public health standards for drug manufacturing," said John M. Taylor, FDA Associate Commissioner for Regulatory Affairs. "Once we discover a company is not following the standards, which were created to ensure safety and quality, we expect them to correct the deficiencies in an expedited manner. American consumers deserve the best health care products on the market today, and companies that are not adhering to these standards cannot assure FDA and American consumers of the quality of their products."

While it is too early to say if the FDA is getting its act together but FDA has not done a terrific job when it comes to drugs like Vioxx, Celebrex, Bextra, Crestor, Tysabri, Adderall, and Prozac.

FDA says that is not aware of any harm to consumers this seizure and it does not believe that the drug poses a significant health hazard to consumers. Consequently, FDA urged patients who use Paxil CR to continue taking their tablets and to talk with their health care provider about possible alternative products for use until the manufacturing problems have been corrected. FDA has determined that Paxil CR is not medically necessary and that alternative products are available for consumer use.

The agency is concerned that GSK's violation of manufacturing standards may have resulted in the production of poor quality Paxil CR that could potentially pose risks to consumers. Among the violations noted during FDA's latest inspection was the finding that the Paxil CR tablets could split apart and patients could receive a portion of the tablets that lacks any active ingredient, or alternatively a portion that contains active ingredient and does not have the intended controlled-release effect.

The seizures follow warrants issued by the U.S. District Courts for the District of Puerto Rico and the Eastern District of Tennessee. The seizures were executed today by the U.S. Marshals Service at GSK's Cidra, Puerto Rico manufacturing facility, its Knoxville, Tennessee distribution facility, and a Puerto Rico distribution facility. GSK has voluntarily recalled some of the affected lots of Paxil CR; however, it has failed to recall all affected lots of these products. This failure on the part of GSK resulted in today's seizures by federal authorities.

GlaxoSmithKline said that the company is working with the FDA to resolve these issues as quickly as possible. In a similar action and for similar reasons, FDA also seized lots of another drug Avandamet, also manufactured by GlaxoSmithKline.

Recommended article: What should you know about safety of prescription drugs?

Avandamet patients hurt by recall and seizures

In a response to ongoing concerns about manufacturing quality, the Food and Drug Administration (FDA) and the Department of Justice today initiated seizures of Avandamet tablets manufactured by GlaxoSmithKline, Inc. (GSK). Manufacturing practices for Type II Diabetes drug Avandamet, failed to meet the standards laid out by FDA that ensure product safety, strength, quality and purity.

"FDA and the Department of Justice will not allow drug manufacturers to ignore our high public health standards for drug manufacturing," said John M. Taylor, FDA Associate Commissioner for Regulatory Affairs. "Once we discover a company is not following the standards, which were created to ensure safety and quality, we expect them to correct the deficiencies in an expedited manner. American consumers deserve the best health care products on the market today, and companies that are not adhering to these standards cannot assure FDA and American consumers of the quality of their products."

While it is too early to say if the FDA is getting its act together but FDA has not done a terrific job when it comes to drugs like Vioxx, Celebrex, Bextra, Crestor, Tysabri, Adderall, and Prozac.

FDA says that is not aware of any harm to consumers by the products subject to this seizure and it does not believe that these products pose a significant health hazard to consumers. Consequently, FDA urged patients who use Avandamet to continue taking their tablets and to talk with their health care provider about possible alternative products for use until the manufacturing problems have been corrected. FDA has determined that Avandamet is not medically necessary and that alternative products are available for consumer use. Approved versions of the individual components of Avandamet (i.e., rosiglitazone and metformin) are available in the same doses as those found in the combination Avandamet tablets subject to seizure, with the exception of the 1 mg dose of rosiglitazone.

The agency is concerned that GSK's violation of manufacturing standards may have resulted in the production of poor quality drug products that could potentially pose risks to consumers. FDA found that some Avandamet tablets did not have an accurate dose of rosiglitazone, an active ingredient in this product.

The seizures follow warrants issued by the U.S. District Courts for the District of Puerto Rico and the Eastern District of Tennessee. The seizures were executed today by the U.S. Marshals Service at GSK's Cidra, Puerto Rico manufacturing facility, its Knoxville, Tennessee distribution facility, and a Puerto Rico distribution facility. GSK has voluntarily recalled some of the affected lots of Paxil CR and Avandamet; however, it has failed to recall all affected lots of these products. This failure on the part of GSK resulted in today's seizures by federal authorities.

GlaxoSmithKline says that in the short term, it is expected that the FDA action will result in a shortage of patient supplies for Avandamet. It added that the company is working with the FDA to resolve these issues as quickly as possible.

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Second Tysabri patient confirmed with PML

It appears that Tysabri problems are worse than initially believed. On February 28, 2005, the drugmakers reported that they had suspended marketing of TYSABRI based on one confirmed case and one suspected case of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal, demyelinating disease of the central nervous system. The investigator has now changed the status of the second case from suspected to confirmed. The companies are continuing to examine these two cases. As indicated in the announcement on February 28, 2005, both patients received more than two years of TYSABRI therapy in combination with AVONEX (Interferon beta-1a). (Related article: FDA advisory on Tysabri)

To date, the companies have received no reports of PML in patients receiving TYSABRI monotherapy for MS or in patients with Crohn's disease or rheumatoid arthritis. Biogen Idec has not received any reports of PML in patients treated with AVONEX alone, a product on the market since 1996.

Biogen Idec and Elan announced that they will work with clinical investigators to evaluate TYSABRI-treated patients and will consult with leading experts to better understand the possible risk of PML. Based on the full results of these evaluations, the companies, in consultation with regulatory authorities, will determine the appropriate next steps.

In addition, Biogen Idec and Elan have undertaken to provide information to the Securities and Exchange Commission (SEC) in connection with the voluntary suspension in the marketing of TYSABRI. The companies are cooperating with the agency regarding these matters. It may be pointed out that some executives of these companies are being investigated for insider trading. They sold their shares days before announcement about Tysabri recall and also awarded huge bonuses to executives.

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FDA refuses to recall Crestor

The FDA has once again failed to act in the interests of American people. If readers may recall, Dr. David Graham, the world-renowned expert at the FDA has charged that apart from Vioxx (and sister drugs like Celebrex and Bextra), there were four other dangerous drugs on the market. Crestor was one of them. Crestor, a member of a class of cholesterol-lowering drugs commonly referred to as 'statins', was approved in the U.S. in August 2003. Many consumer rights group have demanded a Crestor recall.

FDA has simply issued a health advisory against Crestor to re-emphasize recommendations made in the original label about the need for physicians to consider using lower starting doses of the drug in some individuals as a means of reducing the risk of rhabdomyolysis (serious muscle damage).

The revised labeling notes that this may be particularly important for treating Asian American patients, since clinical trial data suggest that they (along with patients on cyclosporine or patients with severe renal insufficiency) may have higher drug levels and therefore be at greater risk for muscle injury due to Crestor than the general population.

Kidney failure of various types has also been reported in patients treated with Crestor, as well as other statins. However, patients who are candidates for statin therapy (e.g., patients with diabetes, hypertension, atherosclerosis, and/or heart failure) also may be at higher risk for kidney failure even when they are not prescribed statin therapy. Based on FDAs review of these cases and the available data from controlled trials, FDA cannot confirm that recommended doses of statins, including Crestor, can cause or worsen kidney failure.

Sidney M. Wolfe, MD, Director, Public Citizen's Health Research Group, criticized the FDA and said that inaction to recall Crestor is yet another example of "the agency's dangerous cowardice in failing to adequately protect people in this country from uniquely dangerous prescription drugs". Below are excerpts from Dr. Wolfe's statement:

Like statements from AstraZeneca, the FDA's statement is replete with false and misleading information. Rather than responding in a public health-positive manner to our March 2004 petition and banning this drug, the FDA has done exactly what AstraZeneca wanted with minimal labeling changes and surely has pleased one of the drug companies contributing to the $150 million in drug industry funding that the FDA is receiving this year for drug review.

Since the last supplement to our petition to ban Crestor (submitted in October 2004), which was based on adverse reaction reports through August 26 of last year, there have been an additional 52 U.S. cases of life-threatening muscle damage (rhabdomyolysis) reported to the FDA and an additional 12 U.S. cases of kidney failure or impairment in people not having rhabdomyolysis reported to the agency up to the end of January of this year. The total of such U.S. cases reported since the drug was first marketed in September 2003 is now 117 cases of rhabdomyolysis and 41 cases of kidney failure, both higher than seen with the other currently marketed statins. Because of concerns about the safety of Crestor, several countries, including Germany, Norway and Spain, have not approved the drug.

Although the increased rate of rhabdomyolysis is not as high as that of the now-banned Baycol, the FDA is well aware that the rate is higher than that of the other statins, a fact it covers up by saying the rate is 'similar.' The FDA statement also includes other 'facts' that are extremely misleading if not false:

FDA Statement: "Data available to date from controlled trials, as well as post-marketing safety information, indicate that the risk of serious muscle damage is similar with Crestor compared to other marketed statins."

Response: Crestor was the only statin that caused rhabdomyolysis at any dose in clinical trials prior to approval. (The cases occurred at 80 mg, a dosage not approved, but most of the post-marketing cases are occurring at 10 or 20 mg.)

FDA Statement: "Mild, transient proteinuria (or protein in the urine, usually from the tubules), with and without microscopic hematuria (minute amounts of blood in the urine), occurred with Crestor, as it has with other statins, in Crestor's pre-approval trial."

Response: Although the FDA admits that with Crestor, "The frequency of occurrence of proteinuria appeared dose-related," it fails to mention that this dose-related increase in proteinuria and hematuria (blood in the urine) was seen only with Crestor and not with any other statin.

FDA Statement: "In clinical trials with doses from 5 to 40 mg daily, this effect was not associated with renal impairment or renal failure (i.e., damage to the kidneys)."

Response: (from FDA medical officer during the July 2003 FDA hearing on Crestor approval): "These three cases of renal insufficiency of unknown etiology are of concern because they present with a clinical pattern, which is similar to the renal disease seen with rosuvastatin in these clinical trials. Proteinuria and hematuria could be potentially managed with regular urinalysis screening. However, if they are the signals for the potential progression to renal failure in a small number of patients, this may represent an unacceptable risk since currently approved statins do not have similar renal effects." (emphasis added)

Rather than being a "Public Health Advisory," as the announcement is titled, this FDA statement is more like an AstraZeneca Health Advisory. In its inability to serve two masters, the FDA has sided once again with its funders in the drug industry.

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