Pharmalot

Next month, the FDA will hold a two-day meeting to discuss the results of a clinical trial for the Avandia diabetes pill, three years after the agency greatly restricted use of the controversial drug. And Steve Nissen, who co-authored a meta-analysis that several years ago found increased cardiovascular risks with the GlaxoSmithKline pill, believes the FDA has a hidden agenda for convening the session.

“The most likely explanation: the leadership of the division of the FDA responsible for drug regulation, the Center for Drug Evaluation and Research, is seeking to avoid accountability for its role in the Avandia tragedy,” he writes in a provocative op-ed in Forbes. Nissen, by the way, is head of cardiology at the Cleveland Clinic.

The meeting, which the agency had ordered, will reassess a clinical trial called RECORD that was, in part, the heated focus of a contentious 2010 FDA panel meeting held to review the Avandia safety record. At the time, both the drugmaker and the FDA were under considerable pressure in the midst of growing public outcry over patient safety and the disclosure of clinical trial data.

In his essay, Nissen notes that Glaxo had secretly conducted an analysis in 2005 and 2006, and concluded its pill increased the risk of heart attacks and related events by about 30 percent. Initially, Glaxo withheld the data from the FDA, but did inform the agency of the findings. But in 2007, his meta-analysis was published, which “intensely embarrassed” the FDA, he maintains.

“Since 2006, CDER has expended considerable taxpayer dollars trying to absolve itself of responsibility for this inexplicable error in judgment that cost many lives. In 2010, CDER and Glaxo saw an opportunity clear Avandia of any cardiovascular hazard and scheduled an FDA Advisory Committee meeting to exonerate the drug,” he writes.

And Glaxo was widely criticized for its handling of the trial. Some FDA scientists claimed the study was flawed and undercounted cardiovascular events. And both the US Senate Finance Committee and the Journal of the American Medical Association chastised Glaxo for attempting to undermine its own scientific steering committee and squelching unfavorable results (more here).

The most significant development at the meeting was a presentation by FDA reviewer Thomas Marciniak, who discussed how the RECORD trial was biased. “For example,” Nissen writes, “the trial was unblinded, meaning that physicians and patients were aware which drug each patient was taking. Even Glaxo was unblinded" (here is the Marciniak review).

“Incredibly, whenever a study site reported a clinical event, GSK and its contract research organization knew immediately which drug the patient was receiving. Marciniak’s review showed that events occurring in Avandia patients were changed or deleted, sometimes months after they should have been reported and counted. These and many other flaws make the RECORD trial totally unreliable.”

Just the same, the FDA ordered Glaxo (GSK) to convene an independent group of scientists to review the RECORD trial. “During the course of the FDA’s review of the RECORD study, important questions arose about potential bias in the identification of cardiovascular events. The FDA is requiring this independent review to provide additional clarity about the findings,” the agency wrote in its September 2010 announcement (...

Despite assorted efforts to get its corporate house in order, Johnson & Johnson simply cannot escape manufacturing problems. The latest escapade has occurred in Brazil, where more than 3.3 million bottles of Tylenol Drops are being recalled because the dripper is apparently malfunctioning and can lead to an overdose.

The active ingredient is acetaminophen, which can cause liver damage, and the J&J notice adds that an overdose can also result in nausea and other gastrointestinal problems. The bottles were made between December 2011 and November 2012, according to a notice issued by the health care giant. We asked J&J for comment and will update you accordingly.

The recall is only the latest in a huge and embarrassing series of such steps by J&J, which earlier this month learned that its Janssen Korea ceo faces criminal charges over manufacturing violations that led to the withdrawal of 1.7 million bottles of Children’s Tylenol.  The government also ordered that J&J had to suspend production of several products for varying periods of time (back story).

As we noted recently, there is irony in the timing. Last month, J&J launched its first new corporate image campaign in more than a decade in hopes of restoring consumer confidence in its products after the huge laundry list of recalls – Tylenol; Motrin; Rolaids; Sudafed; Benadryl; syringes; K-Y Jelly; Accuvue contact lenses; hip replacement devices; and the Topamax epilepsy drug, among many others.

Meanwhile, the health care giant is still trying to remediate a key plant in Fort Washington, Pennsylvania, where its McNeil Consumer Healthcare unit is headquartered, after the facility contributed to a spate of recalls. J&J (JNJ) consequently signed a consent decree with the FDA.

The campaign is also designed to deflect attention away from ongoing investigations and litigation surrounding a scandal over failure data for its hip replacement devices and marketing practices for promoting its Risperdal antipsychotic. In fact, a $2.2 billion settlement with the US Department of Justice is in the pipeline.

The cumulative effect of all these problems earlier this week prompted J&J to ask its employees to reassess its 70-year-old corporate credo, which stresses the need to meet high quality standards. The health care giant hopes employees will then complete a survey to identify "opportunities for improvement and action" (read more here).

STORY ENDS HERE

shock pic thx to ogimogi on flickr

As the US Senate considers legislation to toughen oversight of compounding pharmacies, one group of physicians is lobbying the Senate to create an exception for biologics. The American Academy of Ophthalmology is concerned about a provision in the Senate bill that requires patients to have specific prescriptions for each medicine that is ordered from a compounding pharmacy (here is the bill).

The language is designed to prevent compounding pharmacies from expanding into large-scale production, which is what the New England Compounding Center had been doing before producing medicines that led to a nationwide outbreak of fungal meningitis last year that has been called the worst public health crisis in the US in decades (back stories here and here).

But the AAO argues that the language would have unintended consequences by raising costs for both physicians and patients. Specifically, the physician group notes that such a law would preclude many patients from being able to afford compounded versions of Avastin, a biologic that is widely used for treating age-related wet macular degeneration.

As you may recall, Avastin is an older medication approved to treat various cancers, but not the eye affliction, which is common among the elderly. However, many ophthalmologists use repackaged Avastin on an off-label basis, because the price tag is low – up to $50 for an injection. By comparison, Lucentis, which is approved to treat AMD, can cost up to $2,000 for an injection.

The AAO argues Avastin would become unaffordable. “Ophthalmologist will no longer have the option of having (Avastin) available at the time of their patients’ monthly appointment. If a patient-specific order was placed for that patient prior to their regular monthly examination, the ophthalmologist would be responsible for the product cost if the patient didn’t need it or didn’t show up,” the AAO writes.

[UPDATE: The AAO plea is, so far, being ignored. The Senate Health, Education, Labor & Pension Committee has approved its legislation (see this) and also released a report that justifies the need for giving the FDA greater oversight of compounders.]

Here is some interesting background, though: Both drugs are sold in the US by Roche, which has worked hard to preclude use of Avastin on an off-label basis. Five years ago, for instance, Avastin was pulled from compounders, but its Genentech unit relented after ophthalmologists caused a ruckus, which caught the attention of a US Senate committee that conducted a probe into Medicare expenditures for the drugs.

Medicare costs are a big issue. A study released three years ago found that, in 2008, Medicare paid for 480,000 Avastin injections and 337,000 Lucentis injections, but paid only $20 million for Avastin and $537 million for Lucentis. Avastin was used in 65 percent of Medicare patients, while 40 percent were treated with Lucentis.

In the statement circulating on Capitol Hill, the AAO notes that Medicare will bear the brunt if biologics are not excluded from the patient-specific prescription requirement. Medicare beneficiaries pay an average of $11 for one Avastin treatment for AMD, but $400 per dose for either Lucentis or Eylea, a newer treatment sold by Regeneron Pharmaceuticals (REGN).

At these prices, the annual cost of either approved treatment is about $4,800, while the yearly cost of Avastin to a Medicare...