Drug Injury Watch

FDA Letter Concerning Sybmyax May Result In More Zyprexa Lawsuits For Lilly

According To Bloomberg Report, FDA Wants Information About Weight Gain And High Levels Of Blood Sugar Added To Zyprexa Label

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 29, 2007 Bloomberg published an article by its reporters Rob Waters and Margaret Cronin Fisk about a March 2007 "approvable letter" that the FDA sent to Eli Lilly & Co. on its drug Symbyax, which is a combination of Lilly's antipsychotic drug Zyprexa and the antidepressant drug Prozac.

According to this June 29 Bloomberg article, the March 2007 letter stated that the FDA "would delay the approval of Symbyax for depression because the agency wanted more information about the risk of diabetes in the medicine's prescribing label." 

The reporters said in their article Bloomberg had obtained a copy of this letter by Thomas Laughren, director of the FDA's division of psychiatry products, although "the letter hasn't been publicly released."

Bloomberg's June 29 article provides this content from and description of the Symbyax FDA letter:

"We are concerned that the proposed labeling is deficient with regard to information about weight gain" and high levels of sugar and fat in the blood of patients who took the drug, the FDA said in the letter, referring to proposed prescribing information on Symbyax.  "We do not feel that current labeling for either Symbyax or Zyprexa provides sufficient information on these risks." ....

Lilly's proposed prescribing information for Symbyax failed to disclose that almost half of patients who had high or borderline levels of blood sugar when they started taking the drug ended up with levels high enough to be considered diabetic, the FDA said in its letter. That was more than nine times the number of patients on placebos, or inactive dummy pills.

"We were troubled that this important information was not included in your proposed label," the agency said in the letter.

As covered previously, Lilly has already settled more than 29,000 Zyprexa claims brought by patients alleging that were not adequately warned that Zyprexa can cause diabetes other serious side effects.

As background, the FDA required Lilly and other drugmakers in September 2003 and, again, in March 2004 to warn that Zyprexa and other atypical antipsychotics are associated with weight gain and an increased risk of diabetes.

More recently, this March 2007 FDA letter concerning Symbyax reportedly says that the current label for Zyprexa is still insufficient in terms of its information about the risks of weight gain and blood sugar problems associated with Zyprexa.

As regards the affect of this March FDA letter on the current Zyprexa litigation:  First, it will seemingly benefit the plaintiffs in those cases have been filed but not settled and, second, it may allow additional, new claims to be filed that were previously thought to be barred by operation of the statute of limitations, i.e., filing deadline, in most states.

Safety Of Avandia Discussed At Diabetes Meeting By Doctors Nissen, Buse, And Home

Issues Include Publishing Of May 2007 NEJM Article And Whether To Keep Diabetic Patients On Avandia

(Posted by Tom Lamb at DrugInjuryWatch.com)

A lively discussion during a session about Avandia was the highlight of the American Diabetes Association's annual meeting in Chicago on June 25, 2007 according to news reports.  During a panel discussion of this session -- which was added at the last minute in order to address Dr. Steven Nissen's "meta-analysis" of Avandia data that was published in May 2007 by The New England Journal of Medicine -- some of the 13,000 doctors and researchers in attendance heard Dr. Nissen defend his controversial Avandia study while other prominent doctors took issue with it.

According to a June 25, 2007 report from CNNMoney.com:

... Dr. Philip Home, a professor of diabetes at Newcastle University in the United Kingdom and a member of the steering committee for one of the Avandia studies included in Nissen's analysis, criticized the way Nissen conducted his analysis.

"I think this is data snooping on quite a big scale," said Dr. Home, attacking Dr. Nissen for seeking out data points in pre-existing studies rather than launching a separate study to test a hypothesis. Dr. Home also said he found conflicting results in a study conducted by Dr. Nissen's own Cleveland Clinic.

Also reporting on this Avandia session at the 2007 American Diabetes Association meeting was a June 25, 2007 article from Reuters, which included the viewpoint of Dr. John Buse, the president-elect of this diabetes group, as well as some additional comments by Dr. Home:

Nissen's analysis of the drug, known generically as rosiglitazone, sparked debate because it is based on the pooled data of 42 trials involving nearly 28,000 patients.

"If you take a study not designed to look at heart attacks, can you make a conclusion?" said John Buse, chief of endocrinology at the University of Chapel Hill, North Carolina....

The Nissen study "doesn't answer a question, it asks a question," said Home, who supported the release of Nissen's analysis but criticized the New England Journal of Medicine for not including more context and rebuttal when it was published.

Finally, a Dow Jones June 25 article by reporter Jennifer Corbett Dooren included discussion on the issue of whether Avandia should still be used by diabetic patients:

Dr. John Buse... said if a patient's blood sugar is currently being controlled well using Avandia, then he would not recommend stopping the medication....

He said doctors should be looking toward an FDA panel of outside medical experts for the next set of data involving Avandia or at least a reanalysis by the FDA of the existing studies and possibly some advice on using Avandia. That panel is set to meet July 30.

Buse and other doctors - including Barry Goldstein, the director of endocrinology, diabetes and metabolic diseases division at Jefferson Medical College in Philadelphia - however, said they wouldn't start a new patient on Avandia until more is known about the drug.

This June 25 Dow Jones article also reported that Dr. Nissen "doesn't think Avandia needs to be pulled from the U.S. market...."

No doubt, all interested parties are anxiously awaiting the July 30, 2007 meeting of an FDA advisory panel which will explore the issue of whether Avandia causes heart attacks and strokes.

P.S.  For more insight on what happened at this June 25 Avandia session, see "Avandia Fights: Drs. Nissen And Home 'Battle' Over Drug" over at Pharmas Market with Mike Huckman. (6/26/07)

P.S.  At the U.S. Medicine site, Stephen Spotswood posted an article on June 26, 2007 that does a nice job of re-capping the House Oversight and Government Reform Committee hearing in early June 2007 which examined whether Avandia raises the risk of heart attacks while it lowers blood sugar.  Dr. Nissen and Dr. Buse testified at this Congressional hearing.

Mr. Spotwood's article, "Congress Debates Avandia's Safety, Researchers' Motives and FDA Role", concludes with this report:

Rep. Diane Watson, (D., Calif.), who suffers from type 2 diabetes ended up making one of the most jolting statements of the hearing.

"Two years after I developed [type 2 diabetes] I developed a heart problem," Rep. Watson explained. "I went to my cardiologist and he said, 'What are you taking?' I said, 'Avandia.' And he said, 'Get off it. There are other options out there.'"

(6/29/07)

June 2007 FDA "Patient Safety News" Videos For Doctors Online

Covers Zelnorm, Permax, And Zyvox As Well As Drug Mix-Ups And Hazards of Buying Prescription Drugs Online

(Posted by Tom Lamb at DrugInjuryWatch.com)

The FDA's Patient Safety News (PSN) is a series of monthly video news shows intended primarily for doctors and other health care professionals.  Generally, this series covers significant approvals, recalls, and safety alerts for prescription drugs and medical devices.  Some of the FDA PSN videos contain footage and demonstrations relevant to protecting patients from serious side effects and other unwanted consequences.

Subjects covered in the June 2007 edition of the FDA Patient Safety News include the following:

• Managing Parkinson's Patients Who have Taken Permax
• Market Withdrawal of Zelnorm
• Griseofulvin Anti-fungal Oral Suspension Recalled
• New Safety Concerns about Zyvox
• Preventing Drug Mix-Ups: Bumetanide and Norepinephrine
• Hazards of Buying Prescription Drugs Online

One can find more information about this June 2007 PSN edition and the series in general on the Patient Safety News section of the FDA's web site.

FDA Explains How It Is Trying To Manage Drug Safety Issues

FDA's Paul Seligman Answers Some Questions About The Agency's Drug Oversight Performance

(Posted by Tom Lamb at DrugInjuryWatch.com)

Paul Seligman, M.D., M.P.H., is Associate Director of Safety Policy and Communication in FDA's Center for Drug Evaluation and Research. 

On May 31, 2007 the FDA posted on its web site a Question-and-Answer session with Dr. Seligman regarding how the agency is trying to manage the drug safety issues it has confronted in recent years.  In particular, Dr. Seligman answers this set of questions:

1. Why would FDA approve a drug if it has risks?
2. What factors does FDA consider when weighing a drug's benefits and risks?
3. Why do some safety issues arise after a drug has already been approved for marketing?
4. Where do post-marketing safety reports come from?
5. What kind of action does FDA take after receiving post-marketing safety reports?
6. What if FDA is faced with conflicting drug safety data?
7. Why does FDA inform the public about a potential safety issue if the agency is still weighing evidence?

On May 31, 2007, also, the FDA posted on its web site a piece entitled "Strengthening Drug Safety" which includes the agency's current positions on the following subjects:

• Strengthening the Science
• Improving Communication
• Communications Advisory Committee
• Improving Operations and Management
• Headlines, Hoopla, and Drug Safety

We will continue to monitor and report how the FDA is handling its mandate to ensure the safety of prescription drugs used by patients in the U.S.

Long-Awaited Natrecor Trial Starts To Enroll Patients In June 2007

Scios Inc. Finally Going To Assess Benefit / Risk Profile Of Natrecor In Large Trial Of Patients With Acutely Decompensated Heart Failure

On June 8, 2007 Scios, Inc. let the public know that it has started enrolling patients in a 7,000-patient trial designed to "assess the long-term clinical outcomes and benefit/risk profile of Natrecor (nesiritide) in patients with acutely decompensated heart failure (ADHF)".

According to this June 8 announcement by Scios on the Johnson & Johnson (J&J) web site, Natrecor has previously only been studied in "16 prospective clinical trials involving 2,012 patients", while it has been used to treat "more than 800,000" patients with ADHF since it was approved in 2001.

As background, in June 2005 asked a prominent cardiologist, Eugene Braunwald of Harvard, to convene an advisory panel of heart doctors in order to assess analyses published by two leading medical journals that raised new safety questions regarding Natrecor. Those analyses pooled data from selected tests of Natrecor and estimated the drug may increase the risk of compromised kidney failure by 50%, and of death within 30 days by 74% or more, compared with other therapies.  Soon thereafter, Dr. Braunwald's panel urged J&J and Scios to proceed with a follow-up study to investigate the safety profile of Natrecor.

About a year later, in May 2006 one of the members of that Braunwald panel, Dr. Milton Packer, criticized J&J and Scios for their delay in doing the definitive study that the panel recommended in the summer of 2005.

Now, in the summer of 2007, we learn from J&J and Scios that they are starting to enroll the first patients in this long-awaited Natrecor safety trial.

The June 2007 announcement by J&J and Scios provides these details about this new trial, called Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure, or ASCEND-HF:

In this randomized, double-blind, placebo-controlled, parallel-group, multi-center outcomes trial, approximately 7,000 patients with ADHF will be randomized to receive placebo or NATRECOR® for a minimum of 24 hours up to a maximum of seven days, in addition to standard care.

The primary objective of the trial is to assess whether treatment with NATRECOR® in addition to standard care, compared with placebo plus standard care, improves patient outcomes, as measured by reduction in the composite of heart failure rehospitalization and all-cause mortality through 30 days; or improves heart failure symptoms, as measured by a patient self-assessed dyspnea, or shortness of breath, scale at six and 24 hours after NATRECOR® initiation.

The ASCEND-HF Natrecor trial is being conducted by the Duke Clinical Research Institute (DCRI), which is working in collaboration with the Cleveland Clinic Cardiovascular Coordinating Center (C5).

There was no mention in the June 2007 announcement about when this Natrecor safety trial would be completed nor when its results can be expected.

900 More Zyprexa Lawsuits Settled By Eli Lilly And Co.

Drug Maker Still Faces Product Liability Cases Involving 750 Zyprexa Patients

(Posted by Tom Lamb at DrugInjuryWatch.com)

A June 12, 2007 Associated Press (AP) article reports that the Eli Lilly and Co. has settled another 900 Zyprexa lawsuits.  These legal cases have generally involved allegations by patients that their Zyprexa use has caused diabetes or high blood sugar and that the Zyprexa package insert, or label, failed to adequately warn users of these side effect risks.

In June 2005 Eli Lilly & Co. started reaching settlement agreements with certain groups of plaintiffs' lawyers to resolve these Zyprexa cases.

According to this June 12 AP article about the 900 latest Zyprexa settlements:

• "The Indianapolis-based drug maker declined to release the settlement amount. But spokeswoman Marni Lemons said Tuesday it would have no material impact on the company's financial statements."
• "The company was scheduled to go to trial July 9 in federal court for four Zyprexa claims, but those cases are part of the latest settlement, Lemons said."
• "Lilly has settled roughly 28,500 product liability claims involving Zyprexa over the past two years. In June 2005, the company settled 8,000 claims for $690 million. This past January, it settled more than 18,000 for roughly $500 million."
• "Lilly still faces product liability lawsuits from roughly 750 patients."

Zyprexa is an anti-psychotic Zyprexa used to treat patients who have been diagnosed with schizophrenia and bipolar disorder.

Zyprexa, Lilly's top-selling drug, generated $4.4 billion in sales last year and $1.1 billion during the first quarter of 2007.

Following FDA's Action, Novartis' Zelnorm Gets Recall Order From Chinese Drug Regulator

China's State Food & Drug Administration Says Zelnorm Side Effect Risks Outweigh This Drug's Benefits

(Posted by Tom Lamb at DrugInjuryWatch.com)

A June 8, 2007 Associated Press (AP) article published in The Washington Post reports China's drug regulator has ordered a stop to the production and sales of Novartis AG's Zelnorm in that country.

China's State Food and Drug Administration warned patients to stop taking Zelnorm for irritable bowel syndrome, and said in a statement posted to agency's Web site: "The risks of Zelnorm outweigh the possible benefits for some patients based on analyses from home and abroad."

According to this June 8 AP article about Zelnorm:

The agency said China's National Center for Adverse Drug Reaction Monitoring has received 98 reports of adverse reactions concerning Zelnorm since it was introduced to the Chinese market in 2003. Most involved diarrhea and nausea, with one reported case of abnormally fast heartbeat and another of low blood pressure....

The official Xinhua News Agency said that hundreds of thousands of Chinese patients use the drug.

In March 2007 Novartis agreed to recall Zelnorm in the U.S. at the FDA's request after this constipation drug was linked to a higher chance of heart attack, stroke, and angina (worsening chest pain that can become a heart attack). Later, in June 2007, Novartis was ordered by Swiss regulators to stop selling Zelnorm, which is known as Zelmac in Switzerland.

Emerging Drug Safety Issue Regarding Abbott's TriCor Triglycerides Medication

Barron's June 2007 Report: Experts Are Concerned That TriCor May Cause Decline In Kidney Functions

(Posted by Tom Lamb at DrugInjuryWatch.com)

The weekly business newspaper Barron's reported on June 3, 2007 that some expert cardiologists and nephrologists have raised questions about the safety of TriCor (fenofibrate), a drug from Abbott Laboratories Inc. which is intended to help patients lower their triglycerides, or non-cholesterol fat.

According to a June 3, 2007 Reuters article about this TriCor report:

...some experts say they are concerned that fenofibrate, the generic name of TriCor, may cause decline in kidney functions. Other doctors, the U.S. Food & Drug Administration and Abbott executives say there is no cause for concern, the newspaper said.

There was no immediate comment from Abbott on the Barron's article.

The report comes as analysts predict sales of [TriCor] will grow by double digits in the next few years and Abbott is planning to reformulate it and combine it with a statin to create a product that takes aim at triglycerides and bad cholesterol.

We expect there will be more discussion about this emerging issue about the safety of TriCor in the weeks to come.  As stated in the June 2007 Barron's report, "questions about TriCor seem destined to grow".

P.S.  An earlier Barron's article, "Trials Ahead for a Drug Maker", last updated on June 2, 2007, provided more detail.  In summary, a study by prominent cardiologist Steven Nissen, M.D., published in March 2007 by the Journal of the American Medical Association (JAMA) reported that TriCor causes above-normal increases in a substance called creatinine. Increased creatinine levels usually indicate kidney malfunctions. This earlier Barron's article covers the difference of opinions among medical professionals, along with the views of FDA and Abbott, about whether TriCor is an unsafe drug.  According to this Barron's article, Dr. Steven Nissen's current position: "There is concern raised by the finding but it is not definitive."  (6/5/07)

Novartis Ordered To Recall Zelnorm From Market In Switzerland

Swiss Pharmaceutical Regulator States That Side Effect Risks Outweigh Benefits

(Posted by Tom Lamb at DrugInjuryWatch.com)

In a brief June 1, 2007 Wall Street Journal (WSJ) article it was reported that Switzerland's pharmaceuticals regulator has ordered Novartis AG to recall Zelnorm from the market because the irritable bowel drug's risk of serious side effects outweighed its therapeutic benefits.  In parts of Europe, including Switzerland, Zelnorm is known as Zelmac.

Zelnorm was pulled from the U.S. market on March 30, 2007 after it was linked to a higher chance of heart attacks and strokes.

According to the June 1 WSJ article, the Swiss regulator, Swissmedic, and Novartis disagreed about the safety profile of Zelnorm:

Swissmedic said a new analysis of data from clinical studies revealed an increased risk of angina, heart attacks and strokes when compared with a placebo. Novartis, based in Switzerland, said it is complying with the order but remains convinced that Zelmac has important benefits for certain patients.

According to a May 31, 2007 Reuters article about this Zelnorm recall in Switzerland, that country had approved the use of Zelmac / Zelnorm in women with irritable bowel syndrome in 2001.