As part of its ongoing investigation into the Vytorin controversy, the Senate Finance Committee is disclosing angry notes written by John Kastelein, who was the primary investigator for the Enhance trial, which found the cholesterol pill was something of a dud. The costly combination of Merck’s Zocor and Schering-Plough’s Zetia failed to show a benefit over the much cheaper Zocor in reducing plaque in the carotid artery, and even showed a statistically insignificant buildup, although it did a better job of lowering LDL in patients with an inherited form of high cholesterol.

In other words, Vytorin may not be of much use as a first or second-line therapy, a fact underscored by several prominent docs when the complete Enhance data was dissected at the American College of Cardiology conference this past weekend. And the drugmakers are under a microscope for the way they handled the data - they delayed releasing the study for nearly two years; never appointed an independent board; briefly changed the primary endpoint without consulting Kastelein, and some Schering-Plough execs sold huge amounts of stock.

And so the Senate Finance Committee is trying to connects various dots, such as contributions made by Merck and Schering-Plough to the ACC, which urged its members not to panic when the drugmakers two months ago issued preliminary data. Since 2003, Merck and its various foundations and divisions have donated almost $5 million to the ACC for conference booths, expo fees, educational seminars, and satellite event fees. Schering-Plough gave $1 million. Their joint venture gave another $5 million.

Then there’s Schering-Plough’s ‘49 Plan’ to wine and dine docs in hopes of convincing them to prescribe Zetia, on which $3.5 million is being spent and was first reported by Pharmalot. To keep the pressure on, letters were sent today to Merck and Schering-Plough seeking info about payments to docs. Meanwhile, this is an excerpt from Kastelein’s e-mails to John Strony, a Schering Plough exec:

“Is it correct that (Schering-Plough) has decided not to present at (the American Heart Association), but to await the two other, completely unvalidated, endpoints, which analysis is going to take us straight into 2008??!!?? If this is true, (Schering-Plough) must have taken this decision without even the semblance of decency to consult me as (primary investigator) of the study. I can tell you that if this is the case, our collaboration is over…This starts smelling like extending the publication for no other (than) political reasons and I cannot live with that.”

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Between 2002 and 2006, about 1 billion euros - or $1.6 billion in today’s dollars - was “wasted” by the French health care system as a result of docs prescribing brand-name meds rather than generics in just five classes of drugs. Pourquoi? (Why?) The docs were allegedly under pressure from sales, PharmaTimes writes, citing a report by Union Federale des Consummateurs - Que Choisir (UFC-QUE CHOISIR), a consumer group.

The drugs – used in the treatment of gastroesophageal disorders, blood pressure and arthritis, plus anticoagulants and antiplatelet agents for use in prevention of cardiovascular attacks – account for 14% of prescriptions written by French general pracitioners annually, says the consumer group. And the group cites government estimates that in 2002 alone, half of French scrips for the Plavix bloodthinner were “unnecessary or misprescribed,” costing the system $110 million annually. French health service spending on antiplatelet and anticoagulant agents increased 88 percent in this period.

In France, company reps are permitted to visit only docs, who come under greater detailing pressure than anywhere else in Europe, says UFC-QUE CHOISIR. A report from the Ministry of Labour’s General Inspectorate of Social Affairs (IGAS) has estimated that, in 2005, 22,702 sales reps were operating in France, or one for every nine docs. This is twice as many as in the UK and Germany and four times as many as in the Netherlands, says IGAS, which estimates that this level of detailing costs the industry the equivalent of nearly $40,000 per doc.

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The ongoing controversy over the Provenge prostate-cancer vaccine took a strange twist today. A couple of dozen white roses were sent to FDA commish Andy von Eschenbach late last week and, this morning, a pair of special agents from the agency’s Office of Criminal Investigations visited the Rockville, Md., florist to learn who sent the long-stem missives, according to the florist.

But why was Andy sent roses? And what has this got to do with Provenge? You may recall the FDA last spring ignored the recommendation of its own advisory panel, which met March 29, 2007, and decided not to approve the Dendreon product. This turnabout came after two panel members - Howard Scher of Memorial Sloan-Kettering Cancer Center and Maha Hussain of the University of Michigan - took the unusual step of privately writing Andy and other FDA officials to hold off.

The behind-the-scenes machinations caused a firestorm - the two cancer docs say they received threats; the chain of events fueled debate about the use and approval of experimental meds, and some cancer patients and Dendreon investors filed a lawsuit against the FDA. The suit claims the two panel members held undisclosed financial conflicts of interest and alleged a Byzantine power play involving a key FDA official who sought to sway the outcome, although a federal judge has since tossed part of the suit and an appeal is under way.

To commemorate the event, a few investors and patients were brainstorming about the anniversary and at least two placed orders with All Seasons Florist. A woman who answered the phone and identified herself as Amy says the orders were placed and delivered to nearby FDA offices late last week. She sounded shaken by the visit from the agents, who left their cards, and she identified one as Mark McCormack, who is listed on the agency’s web site as an agent with the FDA’s Office of Criminal Investigations. UPDATE: An FDA spokeswoman writes us to say: “We donated the flowers to a local nursing home. Anonymous, unsolicited gifts are handled according to a standard security protocol to assure they don’t present any safety or security issues.”

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A survey of approximately 1,000 physicians found that Merck was mentioned as a top company by 361 of the respondents, outpacing the 219 mentions given Glaxo, according to Verispan, the market research firm. Merck performed particularly well among primary care physicians and pediatricians, with 48 percent of primary care docs and 52 percent of pediatricians ranking it among the three drugmakers with the best ePromotion programs.

Merck’s spending on ePromotion activities has more than quadrupled over the last 3 years, reaching almost $83 million in 2007, according to Verispan’s ePromotion Audit, which monitors and tracks online pharma promotion to physicians. Merck currently leads the industry in ePromotion investment, accounting for more than 20 percent industry spending for this promotional method, Verispan adds.

Merck’s ePromotion efforts in 2007 were concentrated on primary care physicians with 68 percent of spending, followed by 13 percent spent on pediatricians and 8 percent spent on obstetricians/gynecologists. Merck most often promoted Januvia, Singulair and Vytorin to primary care physicians, and Singulair, RotaTeq and Gardasil to pediatricians. OB/GYNs were most likely to get Fosamax, Singulair and Januvia ePromotions.

A senior member of the Royal Australian and New Zealand College of Psychiatrists resigned as convenor of its 2009 Congress after his peers unanimously voted down a proposal to dump drug-company sponsorship, The Australian reports.

The college was forced last week to appoint two co-convenors to replace Malcolm Battersby, a fellow of the college. RANZC president Ken Kirkby says the college’s more than 20 councillors were not given enough reason to change a policy that complied with the industry’s code of conduct on sponsorships. The policy allows drugmakers to bid against other potential sponsors for naming and signage rights at the event.

“They all felt the proposal lacked substance and wasn’t a suitable way to go,” he tells the paper. “It hadn’t gone through the correct college processes. It was the view of the individuals rather than the college itself.”

The clash highlights the debate about the scale and implications of industry influence over docs, whose prescribing patterns affect not only patient care but the viability of taxpayer-funded programs that subsidize drugs, the paper writes. In the second half of last year, 42 drugmakers spent a total of $31 million paying for “educational events” for health professionals - mostly doctors.

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Patients taking the largest dose of 400 mg twice a day tripled their chance of a heart attack or stroke, compared with people taking a placebo, according to a study presented today at the American College of Cardiology meeting. The study confirms earlier concerns that prompted the FDA three years ago to warn that Celebrex and other painkillers, including ibuprofen and naproxen, should be prescribed at the lowest dose possible, Bloomberg News writes.

“There is clearly an increased risk with increased dose and because this tends to be with the higher doses it probably provides some level of comfort at the lower end of the Celebrex spectrum,” Scott Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital in Boston and the author of the study, tells Bloomberg.

This is the abstract, this is the analysis, and this is Solomon’s presentation.

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Known as Cordaptive, the drug raised HDL cholesterol and caused less facial flushing in a study than Niaspan, an existing med sold by Abbott Labs, but the Merck pill also caused an increase in liver enzymes and had an impact blood sugar for diabetics. The results were described at the American College of Cardiology in Chicago and here is the Merck statement.

Separately, Merck halted enrollment in a different, late-stage study of Cordaptive to consider recent results from similar clinical trials, including a failed study of the cholesterol drug Vytorin. The study, which uses ultrasound imaging as a measure, is testing Cordaptive as a treatment for familial hypercholesterolemia, a rare genetic disorder. The study will continue, but with about 300 people instead of the planned 900 participants. Just the same, Merck still expects an FDA decision on Cordaptive this spring.

The pill contains an extended-release form of niacin, which is a vitamin, and a chemical called laropiprant to stop flushing, a dilation of blood vessels that causes redness and an unpleasant burning sensation on the neck and face. Flushing is a common side effect of niacin-based drugs, and the biggest reason many patients stop taking current products, including Niaspan, Reuters reminds us. Merck contends the problem was largely averted and could boost interest in HDL-raising therapy.

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So who is John Lechleiter? He succeeds Sid Taurel tomorrow at a time when the drugmaker faces several interesting challenges - looming patent expirations, an unimpressive stock performance, pressure to develop new drugs and terrible publicity over government lawsuits charging its Zyprexa antipsychotic was improperly marketed while serious side effect data was hidden.

In an attempt to put a new face on these troubles, the president and chief operating officer allows a reporter from The Associated Press to accompany him on his mile-long walk to the office while he chats about growing up in a crowded household. Lechleiter also emphasizes how he wants Lilly employees to feel connected, so he blogs a bit on his Blackberry and “boasts that no corporate communications rep reviews it beforehand.” It’s not public, though.

And like many execs at big drugmakers, he talks up the Lilly pipeline by emphasizing protein-based drugs being evaluated in the pipeline. And he puts his own special spin on the message. “In a way, we’re a biotech company hidden within what’s called a large pharma company,” he tells the AP. There was apparently no discussion, however, of a 2003 e-mail in which Lechleiter appeared to suggest Zyprexa should be promoted for youngsters; at the time, the med wasn’t approved for kids. Here’s the piece.

A bit of good news, actually, at least for the drugmaker. The trial was halted because the cholesterol pill outperformed a placebo in a study to determine whether Crestor would reduce heart attacks and other cardiovascular problems in patients with no signs of pre-existing cardiovascular disease and low to normal LDL, but elevated levels of CRP, a market linked to heart attack risk.

In a statement, AstraZeneca says the independent monitoring board for its Jupiter study met over the weekend and decided there was “unequivocal evidence” of a reduction in cardiovascular morbidity and mortality among patients on Crestor in the study. This is, of course, a boost for the drugmaker, because Crestor its one of its biggest sellers, and the news contrasts sharply with the growing doubts over the use of Vytorin, which was sullied yesterday at the American College of Cardiology conference.

Not surprisingly, analysts say the decision to halt the Crestor clinical study early, coming on top of Vytorin’s problems, will likely enhance Crestor’s standing and could reinvigorate sales of the product. “It’s a very fortuitous combination for AstraZeneca,” Nomura Code analyst Paul Diggle tells Reuters. Crestor growth slowed towards the end of last year as it battled for market share against generic Zocor and efforts by Pfizer to squeeze more money out of Lipitor.

Some Japanese are questioning standards for cholesterol care after learning that university docs involved in drawing up guidelines received donations from some of the same drugmakers that make and sell meds for metabolic syndrome and high cholesterol, The Daily Yomiuri reports. In fact, the docs received far more cash than other docs. The issue is raising questions about whether researchers who have received corporate donations can remain impartial.

Meanwhile, the paper adds that some experts are skeptical about the guidelines due to their low thresholds, which are capable of categorizing healthy people as being sick and in need of medication. The standard for determining whether a person has high cholesterol is set in line with Japan Atherosclerosis Society guidelines, which defines a total cholesterol count of over 220 as being high. This compares to the U.S. level of 240. Compared with this higher level, patient levels double if the figure of 220 is used.

Tomohito Hamazaki, a professor at Toyama University’s Faculty of Medicine, says that if the lower figure is used, half of all middle-aged and elderly women would be diagnosed as having high cholesterol. “The number of patients has been increased unnecessarily, which resulted in an excessive use of drugs,” he tells the paper.

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