Thursday, October 21, 2010

Wolfe vs. Rappaport (Part 2): Embeda Warning Letter Raised During Abuse-Resistant Opioids Ad Comm

Advisory committees are always interesting, but you really have to expect the unexpected when Public Citizen Health Research Group Director Sid Wolfe is on the panel.

The last time the FDA Drug Safety & Risk Management Advisory Committee member participated in a panel discussion, he wanted to discuss a past off-label promotion settlement during a review of a pending application from Jazz Pharmaceuticals seeking an expanded label for sodium oxybate to treat fibromyalgia.

As we reported at the time, Wolfe was cut off by the committee chair and then chastised by Division of Anesthesia & Analgesia Products Bob Rappaport for bringing up a topic that was not relevant to the discussion—and for not at least bringing it to the agency’s attention in advance as something he wanted discussed. As we first reported, Rappaport then read into the record a statement essentially telling the committee to disregard the issue.

To us, it seemed like Wolfe had a point, that a discussion focused entirely on the appropriate method for marketing a drug like sodium oxybate should at least consider the question of whether the sponsor would or would not actually follow the pathway set down by the agency. Whether or not the committee agreed with Wolfe on that point, they agreed almost unanimously that Jazz needed to rethink its approach to managing this product in the post marketing setting, and voted overwhelmingly against approval. (The agency formally rejected the application this month.)

Wolfe is back on a panel today, part of a meeting to review post-marketing study requirements for opioids that are designed to be abuse resistant. The purpose of the meeting is to determine what standards FDA should set for demonstrating abuse resistance in the real world. (Read the preview in "The Pink Sheet" DAILY, here.)

That is a fascinating topic in itself; probably a glimpse of the future (or a potential future) for essentially all big drug classes.

But the meeting began with Rappaport pointing out an unusual late addition to the committee’s briefing materials: a copy of the warning letter FDA sent to King Pharmaceuticals in 2009, shortly after it launched the abuse-resistant product Embeda. The letter, Rappaport noted, is not the type of thing FDA typically gives to committees, but Wolfe emailed the agency yesterday to ask for it to be distributed. And so it was handed out at the meeting (even though, Rappaport stressed, it is a marketing issue and so not really relevant to a scientific discussion about post-marketing study designs).

The letter hasn't been mentioned since--but King doesn't present until tomorrow morning.

King’s management team told us in an interview earlier this year that the video news releases that prompted the warning were a mistake that it would not repeat. But—as we discussed here—it certainly sets a standard for getting off on the wrong foot with an important new product.

And Wolfe, at least, sees it as evidence that FDA cannot rely on sponsors to do things the right way when it comes to making sure new drugs are used appropriately. So far (the meeting is two days and things are just getting going), Wolfe is pushing for more of the research in the pre-market setting. That doesn't seem to be getting any traction with FDA.

Interestingly, Wolfe doesn’t seem to have asked for any materials to be shared on the other product directly affected by the ongoing meeting: Purdue’s Oxycontin. That company, of course, was prosecuted for misbranding, with the government claiming Purdue’s marketing helped contribute to the widespread abuse of the drug.

Since the entire FDA effort on abuse resistance essentially flows from the Oxycontin controversy, Wolfe apparently doesn't feel like he needs to do anything to draw that connection for the committee.

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