The health-care-fraud unit of the US Attorney’s Office in Massachusetts is investigating whether the drugmaker promoted Vioxx to health-care professionals for uses other than those approved by the FDA, otherwise known as off-label marketing, The Wall Street Journal reports. The probe comes as Merck hopes to proceed with a $4.85 billion settlement with thousands of people who allege they were harmed by the painkiller.

Merck declined to comment. Last February, however, the drugmaker disclosed in its regulatory filings that the Justice Department issued a subpoena requesting info to its research, marketing and sales of Vioxx as part of a federal investigation under criminal statutes. Merck also disclosed in that filing that 31 state attorneys general and the District of Columbia are investigating Vioxx sales and marketing.

Justice Department probes into marketing have resulted in settlements of $875 million with TAP Pharmaceuticals in 2001 and $355 million with AstraZeneca in 2003. And Lilly is negotiating with federal prosecutors who are investigating the marketing of the Zyprexa antipsychotic.

The agency posted a warning on its web site this afternoon about an increased risk of suicidal thoughts and behaviors associated with 11 drugs used to treat epilepsy and certain psychiatric disorders. The drugs include Pfizer’s Lyrica, which is approved for treating pain associated with diabetes and fibromyalgia; Johnson & Johnson’s Topamax, which is also approved to treat migraines; and Glaxo’s Lamictal.

“Patients who were treated for epilepsy, psychiatric disorders, and other conditions were all at increased risk for suicidality when compared to placebo, and there did not appear to be a specific demographic subgroup of patients to which the increased risk could be attributed. The relative risk for suicidality was higher in the patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions,” the FDA wrote.

After examining nearly 200 clinical trials, the FDA saw approximately twice the risk of suicidal behavior or ideation, or 0.43 percent, compared with 0.22 percent of patients receiving a placebo in studies involving about 44,000 patients. The increased risk was seen as early as one week after starting an anti-epileptic drug and continued through 24 weeks. The agency plans to discuss the data at an upcoming advisory committee meeting.

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A whistleblower lawsuit brought by two former sales reps for Johnson & Johnson’s Ortho-Biotech unit was dismissed earlier this week by a federal judge in Boston, who ruled that the pair didn’t clear several hurdles needed to prove their allegations under the False Claims Act. In doing so, however, the judge seems to have ignored an appeal court that last fall reinstated another whistleblower suit that was originally bounced, in part, for similar reasons.

First, some background. Mark Duxbury (pictured) and Dean McClellan peddled Procrit, an expensive med used to treat anemia caused by chemotherapy (you can read more about them here). They alleged Ortho-Biotech gave kickbacks to docs and hospitals to induce them to prescribe Procrit, including free samples; off-invoice discounts; rebates; consulting fees; educational grants; payments to participate in studies, and advisory board fees. They also charged Ortho-Biotech inflated Procrit’s average wholesale price; promoted higher dosing than what was approved by the FDA, which generated larger government reimbursements to health care providers; and ran “sham drug trials” to falsify Medicare reimbursement for off-label use.

The Department of Justice, however, declined to join the case. The biggest setback, though, came on Monday, when US District Court Judge Rya Zobel dismissed the claim. One reason - she decided the alleged false claims were publicly disclosed before the suit was filed, raising questions about whether the former reps were the original sources of info used to make the allegations. (This is the ruling).

Another key reason was their failure to meet the requirements of rule 9b, a controversial provision of the False Claims Act, which requires a whistleblower to provide specific information about false claims that were submitted to the government for payment. Generalizations aren’t sufficient; examples with details about amounts charged, individuals involved in billing and identification numbers, among other things, are desired.

But Zobel chose a strict interpretation.”Although Duxbury identifies providers and approximate amounts of free samples, discounts, ‘off-invoice’ rebates, and educational grants, he fails to identify a single false claim consequently filed by these providers,” Zobel writes in her Jan. 28 ruling. The same reasoning, by the way, was used to bounce a lawsuit brought against Pfizer by whistleblower Peter Rost, but an appeals court reinstated his suit last fall.

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Three more lawmakers have added their names to the list of congressman who have asked the House Energy and Commerce Committee to hold a hearing into allegations that undislosed financial conflicts of interest among FDA advisory committee members may have swayed an FDA decision to delay approval of Provenge, a prostate cancer vaccine being developed by Dendreon.

Vern Buchanan, a Florida Republican, Chris Van Hollen, a Democrat from Maryland, and Pat Murphy, a Pennsylvania Democrat, each wrote letters to John Dingell, who chairs the committee, to urge him to investigate. “As a member of Congress, I believe we must provide the necessary oversight to ensure that the federal approve process of life-saving therapies such as Provenge is prompt and efficient,” Buchanan wrote.

Last month, Mike Michaud, a Maine Democrat; Dan Burton, a Republican from Indiana, and Tim Ryan, a Democrat from Ohio, were the first members of Congress to take an interest in the controversy. Here is the Buchanan letter and this is the Murphy letter. The Van Hollen letter is to the right (please click for a larger image).

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As a result, Thailand’s public health minister, Mongkol na Songkhla, cancelled a compulsory license for the leukemia drug. Novartis made a last minute offer agreeing to a government condition to provide Gleevec free to all patients under universal healthcare as a trade-off for not seeing its patent overriden, The Bangkok Post reports.

Novartis had previously insisted Gleevec would be provided for free only for patients who earn less than $9,600 a year. Mongkol had turned down the offer because health statistics showed that 10 million of the 48 million people under the state healthcare scheme would not be eligible, according to Vichai Chokewiwat, who chairs Thailand’s Government Pharmaceutical Organization.

An estimated 900 poor patients under the scheme, who have chronic myeloid leukaemia or another rare type of cancer, gastro-intestinal stromal tumour, could receive Gleevec through a philanthropic program to be sponsored Novartis. The drug is not available to the majority of people because of its high cost, about 3,600 baht, or $114 per tablet. Full treatment costs a patient up to $41,600 a year.

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Wyeth forecast flat revenue and lower earnings for this year due to generic competition for its blockbuster Protonix heartburn med and other generic competition. The forecast hinges on keeping R&D spending flat and trimming other expenses, such as 10 percent of its workforce. The drugmaker reported fourth-quarter earnings rose to $1 billion, or 75 cents, from $855 million, or 63 cents, a year ago, on higher sales of its Enbrel arthritis drug and Prevnar vaccine. Excluding one-time items, profits were 78 cents. Revenue rose 10 percent to $5.8 billion. Read more here and here.

Bristol-Myers Squibb narrowed its loss in the fourth quarter thanks to rising sales of its Plavix bloodthinner, which partially offset charges including investments backed by sub-prime securities. Net loss was $89 million, or 5 cents, compared with a loss of $134 million, or 7 cents, a year earlier. Profit from continuing operations excluding some items was 35 cents a share, beating the 34-cent average estimate of 16 analysts surveyed by Bloomberg News. Revenue rose to $5.4 billion from $4.1 billion. (This is the earnings release).

IMS Health reported a lower fourth-quarter net profit on restructuring charges. Net income was $18 million, or 9 cents a share, compared with $65.5 million, or 32 cents per share, a year ago. The restructuring charge of $88.7 million reduced fourth-quarter earnings by 32 cents a share; excluding charges, the company earned 43 cents. Here’s the complete statement.

Celgene reported fourth-quarter net income of $75.3 million, or 18 cents, up from $22.9 million, or 6 cents, a year earlier, while revenue rose 51 percent to $414.6 million. Sales of Revlimid, Celgene’s flagship cancer drug, doubled to $247.4 million. You can the complete statement here.

Novo Nordisk posted a 2 percent drop in 2007 operating profit, but beat analyst expectations and forecasts higher profits this year. The world’s biggest maker of insulin reported earnings before interest and taxes fell to $1.77 billion, while sales rose 8 percent. Read more here.

Just what can happen when a clinical trial goes awry and a participant is hurt? Take the example of Suzanne Davenport. The Wall Street Journal chronicles how she entered a trial testing a drug for Parkinson’s disease - before the trial, she could drive, cook and care for herself. Within months, she was in a wheelchair in a nursing home. Her family says the trial caused her precipitous decline and, faced with growing medical bills, filed a lawsuit againt the two drugmakers that ran the trial and the university that enrolled her in the trial.

The case highlights one aspect of the legal and regulatory void surrounding clinical trials, the Journal points out. That’s because federal law doesn’t require researchers to compensate participants harmed in trials - they’re only required on their consent forms to spell out whether compensation will be available for research-related injuries in trials that involve more than minimal risk.

The prospect of compensation for injuries can encourage volunteers who might otherwise be reluctant, the paper continues, but adds that wording in consent forms can be confusing or vague. For instance, it may be unclear which research entity is responsible for the cost of subsequent care, how much that entity will pay and under what circumstances it is obligated to pay, the Journal writes.

One big problem is that it can be difficult to separate what was caused directly by a trial from the natural progression of a participant’s disease. Drugmakers “do not want to end up paying for all of somebody’s care when that care may simply be the product of the fact that that person had a grave illness,” Haavi Morreim, a University of Tennessee bioethics professor who has studied clinical-trials lawsuits, tells the Journal. We raised this issue recently concerning omissions in consent forms for Merck’s Vioxx trials, which you can read about here.

The issue is gaining attention as drugmakers face increasing financial pressure to develop new meds and so are conducting more clinical trials. World-wide, the number of industry trials rose to 59,000 in 2006 from 40,000 in 2000, according to an estimate from CenterWatch, the Journal writes.

You can read the rest of the story here, but a subscription may be required. [Make sure to take a look at the documents. For instance, there are links to the university consent form signed by Davenport; the contract between the university and the drugmaker; the consent form prior to her surgery, and a series of exchanges between her daughter, the drugmaker and the family attorney.]

A big state-owned Chinese drugmaker that exports to dozens of countries, including the US, is at the center of a nationwide scandal after nearly 200 Chinese cancer patients were paralyzed or otherwise harmed last summer by contaminated leukemia drugs, The New York Times reports.

Chinese drug regulators have accused the manufacturer of a cover-up and closed the factory that produced them. In December, China’s FDA said Shanghai police began a criminal investigation and two officials, including the head of the plant, had been detained, the Times writes. The drugmaker, Shanghai Hua Lian, is the sole US supplier of the abortion pill, mifepristone, or RU-486, although the paper notes it’s not made at the same factory that produced the tainted cancer drugs.

The FDA declined to answer the paper’s questions about Shanghai Hua Lian, citing security concerns stemming from opposition to abortion. But in a statement, the agency tells the Times the plant passed an FDA inspection in May. “FDA is not aware of any evidence to suggest the issue that occurred at the leukemia drug facility is linked in any way with the facility that manufactures the mifepristone,” the statement said.

Last October, Pharmalot wrote that a conservative group, Judicial Watch, released documents indicating the pill is made by Shanghai Hua Lian. Given concerns over meds made in China, the group was clearly trying to create controversy, beyond any ongoing moral debate. (You can view documents here; please turn to page 8 and look for NDA 20687, which was the new drug application number assigned mifepristone).

When told of Shanghai Hua Lian’s troubles, Sid Wolfe of Public Citizen tells the paper the FDA ought to be concerned because of accusations that serious health risks had been covered up. “Every one of these plants should be immediately inspected.”

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Another day, another earnings report, or two. And who knows what else? As we assemble another interesting tale, we are also hunting and gathering all sorts of items. Here are a few for you. So grab your coffee or tea, or bottle of water, and catch up with the rest of us…

AstraZeneca reported fourth-quarter profit declined as cutbacks and acquisition costs swelled while demand for its biggest meds slowed. Net income fell 12 percent to $1.3 billion, or 86 cents a share, from $1.43 billion, or 93 cents, a year earlier, while sales increased to $8.2 billion. The drugmaker is eliminating 7,600 jobs, or 11 percent of its workforce. Meanwhile, the Nexium heartburn med and the Crestor cholesterol pill slowed because of competition from cheaper generics, a trend that will be exacerbated by Wyeth’s new generic Protonix. (Read the AZ statement).

Daiichi Sankyo’s Injectafer, which the company proposed selling for iron deficiency anemia, may pose “serious safety concerns,” according to the FDA. The intravenous drug was linked in studies to more deaths, heart failure and lower blood phosphate than comparable treatments, agency reviewers wrote in a document posted today on the FDA web site. An advisory panel meets tomorrow.

Glaxo has asked European regulators to approve a vaccine protecting young children against meningitis, pneumonia and ear infections that would challenge Wyeth’s Prevnar, Bloomberg News reports. Known as Synflorix, the vaccine would prevent illnesses caused by two bacteria, and immunization would also fight three types of one of the bacteria, which are linked to severe pneumococcal disease. Synflorix would be the first competition for Prevnar.

The drugmaker is talking to federal prosecutors about settling civil and criminal investigations into its marketing of the antipsychotic and the money would be paid to federal and state governments, The New York Times reports. If a deal is reached, the fine would be the largest ever paid by a drugmaker for breaking the federal laws that govern how pharma can promote medicines.

Zyprexa has serious side effects and is approved only to treat people with schizophrenia and severe bipolar disorder. But documents from Lilly show that between 2000 and 2003, Lilly encouraged docs to prescribe Zyprexa to people with age-related dementia, as well as people with mild bipolar disorder who had previously been diagnosed only as depressed, the Times writes. Lilly may also plead guilty to a misdemeanor criminal charge, but would be allowed to continue selling Zyprexa to Medicare and Medicaid, the biggest Zyprexa customers, according to the Times.

Lilly would neither confirm nor deny the settlement talks. “We have been and are continuing to cooperate in state and federal investigations related to Zyprexa, including providing a broad range of documents and information,” Lilly said in a statement today to the Times. “As part of that cooperation we regularly have discussions with the government. However, we have no intention of sharing those discussions with the news media and it would be speculative and irresponsible for anyone to do so.” Lilly also said that it had always followed state and federal laws when promoting Zyprexa.

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