Tuesday, August 02, 2011

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

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