It's Not About Life-Cycle Management. Really.

Here's the latest fuel for pharma industry critics' fire: Axanum. This drug, a fixed-dose combination of AZ's PPI Nexium (esomeprazole) and low-dose aspirin, received positive agreement for approval Aug. 2 via Europe's de-centralized procedure. By trying to tag Nexium, which loses exclusivity in 2014, onto the back of widely-used low-dose aspirin, AZ, critics may say, risks falling foul of industry's (and its own) claims to be delivering innovation and value-for-money.

Shame on you AstraZeneca, we were going to say. But then we thought, fair enough. The company's under pressure right now, with 80% of its global revenues at risk over the next five years. Meanwhile the more honourably (and obviously) innovative Brilinta, a better-than-Plavix heart drug approved by FDA in July, may be held back by another kind of relationship with aspirin: Brilinta works less well when used in conjunction with high-doses of the drug.

Still, it may be a bit rich to suggest that this drug isn't about protecting the Nexium patent and franchise. Instead, Axanum will fulfill "a clear unmet need for patients that who require low-dose ASA (posh word for aspirin) to prevent CV events, but who risk discontinuing their treatment due to low-dose ASA-related upper GI problems," says the company.

FDA didn't buy it. They bought Vimovo, a Nexium-naproxen cocktail developed with Pozen for osteoarthritis, in 2010, but Axanum got slapped that same year with a Complete Response Letter, as did AZ's attempt to expand Nexium's label to include reducing the risk of low-dose-aspirin-associated peptic ulcers (same ends, different means).

Europe offers drugmakers an alternative route-to-market when the centralized European Medicines Agency path looks risky, though – or when medicines don't qualify for it. Biotech, orphan drugs, gene therapies and those falling into one of six TAs (not including CV or GI) have to go through EMA; those outside these groups can choose to only if they offer "significant therapeutic, scientific or technical innovation".

AZ says it filed Axanum via the decentralized process in 2009 to "reflect markets' interest", but whatever the reason (choose from above), it allowed the Big Pharma to select a reference state (Germany) to approve the product, which other countries could then follow (or not). Apparently 22 European countries, plus Norway, have followed, agreeing to approve Axanum for prevention of CV events in patients taking daily low-dose aspirin who are also at risk of gastric ulcers.

The company claims about a third of high-risk CV patients are also at increased risk of stomach ulcers, and that GI problems are the main reason for stopping low-dose aspirin. "Axanum is the only medicine that ensures every single pill of low-dose ASA comes with built-in protection against gastric ulcers," says the release.

Patients could just take aspirin with some Nexium, though (or, dare we suggest, a bit of generic omeprazole?) AZ claims that, although taking the monotherapies separately "has been demonstrated to be effective," in high-risk CV patients, the CV treatment can't be compromised, and that current adherence to PPIs is poor among low-dose aspirin patients (patients aren't taking enough Nexium, in other words).

"The combination is based on valid therapeutic principles such as simplification of dual therapies," asserts the company.

Improving compliance is an important – and potentially cost-saving – health care benefit. So good luck to AZ in its ongoing pricing discussions with European reimbursement authorities. But with generic PPIs floating about, don't let's hold our breath for a premium. Vimovo's hardly flying off U.S shelves -- and we hear that Pozen thinks it's because AZ tried to push the price too high.

image by flickrer Will Norris used under creative commons

Was Tom Scully Right About Nexium?

You probably remember when Tom Scully was the head of the Centers for Medicare and Medicaid Services.

If you do, you may also remember his rants about successor products companies create to offset generic competition for one of their brands. He was particularly concerned about the amount of taxpayer money being spent to cover AstraZeneca’s Nexium. The company’s original proton pump inhibitor omeprazole (Prilosec) works just as well, he maintained – and extremely cheap omeprazole generics are available, as are over-the-counter versions.

Here’s a sample of what Scully said about Nexium back in 2003 and 2004:

• "The fact is, Nexium is Prilosec. It is the same drug. It is a mirror compound. It is exactly the same."
• "You should be embarrassed if you prescribe Nexium because you're screwing the patients and you're screwing taxpayers.”
• “Nexium is a game that is being played on the people who are paying for drugs, and it's not right."

Get the picture? Mr. Scully isn’t a fan of Nexium, at least when it comes to the government paying for it.

Well, now CMS has released some of its findings from an examination of Part D drug claims data from 2006 and 2007, and guess what? It looks like Tom had a good reason to be concerned. Nexium is the fourth largest drug in the program by cost. Only Lipitor, Plavix and Zyprexa have a larger claim to Part D dollars.

CMS says gastrointestinal drugs accounted for 8.7% of overall drug costs, and presumably Nexium is a big chunk of that, given its fourth-place ranking. TAP’s PPI Prevacid also contributed significantly to spending in the category, coming in seventh overall.

Interestingly, proton pump inhibitors seem to be the drugs Part D beneficiaries think they can do without when they reach the donut hole and have to cover the full cost of the drugs themselves.

A recent study by the Kaiser Family Foundation found that, on average across eight drug categories, 15 percent of Part D enrollees stopped taking their medicines when they fell into the donut hole, but the highest rate of discontinuation was for PPIs, at 20 percent.The study said, “Because there is some concern that PPIs are overused for more routine gastrointestinal conditions, terminating medication use might not pose serious health risks in some cases.”

There’s been a lot of pushing by the plans to use low-cost drugs by having lower copays for generics than brands. One problem with differential copays in Part D is that many of those enrolled in the program are eligible for a low-income subsidy from the government, and they are protected from the higher copays for brands. As a result, they don’t respond to the financial incentives provided by differential copays to take the cheaper drug.

Plans are starting to respond to that by putting stricter drug utilization management rules, like prior authorization and step therapy, in place for those beneficiaries. The biggest Part D plan sponsor, UnitedHealth, is taking that route, as detailed in a recent article in “The Pink Sheet.”

So what would Tom say about this data? I asked him, and he was nice enough to provide a few thoughts by e-mail. First, he wished to say that he has no grudge with Nexium per se, and if someone wants to pay for it in a private plan, that’s just fine with him, but “no government insurer should pay for Nexium as an added cost to Prilosec. … My last year at CMS I think Medicaid spent $350 M on Nexium – absolutely insane.”

And, not to rub it in or anything, but he did have this final reaction to all the money being spent on Nexium in Part D: “I told you so.”--Scott Steinke

image by flickr user shoothead used under a creative commons license

FDA’s Risk Communication Advisory Committee: An Ineffective Beginning

If you’re an executive for a company with an FDA-regulated product, the agency’s inaugural Risk Communication Advisory Committee meeting had to make you a little nervous.

Granted this was the first time the group was brought together so you’d expect some wandering by the committee. Still, there was a lot of wandering. And the last thing the industry or the agency needs is more unknown variables thrown into the risk communication equation. From the hour-long introductions on the first day to the back-and-forth open public hearing portion of the meeting, the committee was like a Super Bowl half-time show gone bad. There appeared to be little focus on any particular area of discussion and much of the conversations between panelists lacked meaningful direction—a telltale sign of a bad committee.

Here’s the issue for biopharma companies: FDA typically follows advisory committee recommendations, although they certainly aren’t required to. With a committee this inexperienced and seemingly unfamiliar with FDA regulations, procedures and protocols, how will their opinions be interpreted into final risk communication decisions? How will the media report recommendations from a newborn committee that may be clearly out of whack with FDA standard procedures?

The Institute of Medicine’s report on drug safety called for the creation of a risk communication advisory panel similar to FDA’s other scientific drug review committees except focused on how FDA should best communicate safety and risk-related issues to the public.

In other words, how to alert the public without alarming them. To read our initial story on the new committee, click here.

What FDA, and the drug industry for that matter, really requires from this committee is a strong group of advisors to provide practical guidance to FDA on how to address risk concerns quickly, proportionally to the risk presented with new information emerging continuously. If the inaugural meeting serves as any guidepost, FDA won’t be getting that guidance.

The agency has had a mixed record recently dealing with these types of situations. In May, FDA was criticized heavily for reacting too slowly to the publication of meta-analysis data on GlaxoSmithKline’s diabetes drug Avandia showing more than a 40% increased risk of heart attack associated with patients using the drug. In fact, the House Committee for Oversight and Government Reform was able to announce a hearing before FDA could even respond to the analysis with a press release or conference call. We all know how that turned out.

Then there was a rather awkward “early communication” call in August with the media over potential cardiovascular risks linked to AstraZeneca’s blockbuster proton pump inhibitor Nexium found in two small studies. But after discussing the possible risks uncovered by the trials, the agency said on the same call there were no risks related to Nexium. “FDA has concluded preliminarily that these data do not suggest an increased risk of heart problems for patients treated with either of these products,” Center for Drug Evaluation and Research associate director for safety policy and communication Paul Seligman said.

The Nexium communication was followed by a January “early communication” briefing by FDA on Merck/Schering-Plough’s ENHANCE study of the cholesterol combo drug Vytorin almost two weeks after data from the study were made public by the companies and commented on at length by cardiologist Steve Nissen in the mainstream media.

On the call, FDA officials summarized the results already made public by Schering-Plough, and said it would review the data fully once it is submitted by the sponsor. To read a recap, click here.

The risk communication committee is supposed to help FDA avoid situations like that. What the agency appears to have on its hands, though, is a motley crew of experts with very different fields of expertise who don’t necessarily fit together or fit the purpose they were meant to serve—at least based on the initial two-day meeting.

The purpose of this first meeting was not to make specific recommendations on a specific product or issue but rather a more general discussion of risk communication. So there will be wandering. What should be alarming to drug companies, however, is how pronounced the absence of direction was during question and answer sessions and the level of inexperience displayed by individual panelists.

FDA senior risk communication advisor Nancy Ostrove explained in her overview presentation to the panel that this particular committee is supposed to be different. But in this case, different does not necessarily mean better.

The open public hearing encapsulated how the two-day meeting went. A free-lance reporter spoke endlessly (public speakers are generally given five minutes to make a statement during advisory committee meetings, this went way over) about how reporters used to be able to interact directly with FDA officials but now must go through the press office to seek permission to speak with an official and often aren’t granted access. Committee chairman Baruch Fischhoff, Carnegie Mellon, and other panelists engaged in a prolonged Q&A session with the speaker. It was painful.

Not everything was bad. FDA assistant commissioner for accountability and integrity William McConagha delivered a clear and important presentation on legal authorities and protections related to the First Amendment and communicating risk. One interesting suggestion to come out of the meeting from consultant Steve Gorelick, Hunter College, was that FDA hold a daily media briefing similar to the Pentagon.

All in all, though, the first risk communication panel meeting was a dud. Although it takes time for FDA advisory committees to develop personality and voice, this is one committee that won’t be afforded the time to do that. With arguably unprecedented public scrutiny of FDA and the next drug safety event around the corner, the agency will need to mine the expertise of the panel—sooner rather than later.