Disappointing Crestor Results For AstraZeneca
19 CommentsBy Ed Silverman // September 2nd, 2011 // 6:57 am
And so, a calculated bet has not paid for the drugmaker. In a head-to-head trial called Saturn, imaging tests showed patients on Crestor had a lower percentage of artery-clogging plaque than those on Lipitor, but the difference was not statistically significant. Crestor did show a significant improvement over Lipitor in a secondary endpoint.
The purpose was to convince doctors that Crestor had a significant advantage in hopes of maintaining prescriptions as lower-cost generic versions of Lipitor arrive later this year. The disappointing results, however, mean that “payers could push back even harder against usage of the drug downstream of Lipitor generics,” according to a recent investor note by Sanford Bernstein analyst Tim Anderson. He added that the imaging method used is a “reasonable, but imperfect proxy” for heart attack risk.
This results are, of course, very important to AstraZeneca, since Crestor generated $5.7 billion in revenue last year, although sales were still expected to slow. “A lot of people were hoping the study would differentiate the two,” Navid Malik, an analyst with Matrix Corporate Capital, tells Bloomberg News. “I don’t think it will now.”
The study compared the effect of 40mg of Crestor and 80mg of Lipitor on plaque build-up in the arteries of patients with heart disease. The amount of plaque was measured two ways, by total volume and percentage volume. Crestor reduced the total volume of fatty deposits in the artery more than Lipitor, but on a percentage basis, the result wasn’t statistically significant (here is the AstraZeneca statement).
The failure of the study to reach statistical significance “calls into question the rationale for use of the 40mg dose altogether,” Matrix Group analyst Navid Malik writes in an investor note, according to Pharma Times. And the outcome “potentially muddies the water on the data previously seen in the Jupiter study” which compared the pill to a placebo and resulted in a label change.
However, in his own investor note, Leerink Swann analyst Seamus Fernandez writes that, “while we see little reason for physicians to continue prescribing the lower 5 & 10 mg doses of Crestor, which currently represent 60 percent of total Crestor prescribing, some of our contacts point to 3-year contract for Crestor that will maintain the drug’s formulary positioning until 2014.”
thumbs down thx to italianvoice on flickr
Justice in MI
It’s probably in there somewhere, but I’m missing what the “secondary endpoint” was for which Crestor showed significant improvement? Thanks.
Justice in MI
Found my answer in the Pharma Times link, TAV vs. PAV. Not that I know the significance of the significance.
John English
Justice - Your second comment reminds me of the quote from Mark Twain: “Facts are stubborn things, but statistics are more pliable.”
Observant Earthling
“Win” for that comment, John English!
original industry insider
This is where the Marketing folks get paid the big bucks. The challenge is how to spin numerical superiority on a primary endpoint and statistical superiority on a secondary endpoint into something promotable.
Knowing how marketers think, I’m sure that by now the AZ biostatisticians are spending their holiday weekend cooking up reams of post hoc “combined endpoints” where Crestor comes out on top, and I’m also pretty sure that Marketing has ordered them to present the “new and improved” analyses first thing Tuesday morning.
The brain of a marketeer works as follows: if we can get out a new promotional piece favoring Crestor over Lipitor, even if it contains false and misleading information, we’ll be able to get six months out of it before FDA makes us pull the ad. If we can score one or two extra billion in profits during that period, then all the better.
Stay tuned.
original industry insider
AZ just lost $1.8 billion in market capitalization based on the results of SATURN. They need find a way to make up the loss, by hook or by crook, which reinforces what I think will be the marketing strategy from my post above.
http://www.wikinvest.com/stock/AstraZeneca_(AZN)/Data/Market_Capitalization
http://finance.yahoo.com/news/Astrazeneca-shares-fall-on-apf-2830627491.html?x=0&sec=topStories&pos=7&asset=&ccode=
Justice in MI
Indeed. Unfortunately, internal materials released via litigation, qui tam suits for off label promo and product liability, confirm OII’s comments.
Have also seen a few spin jobs for drugs I know well. They were, indeed, successful–docs I know believing the “superiority” claim based on promos, without knowing that no statistical significance (or ignoring that lack).
It works.
keiner
Help is under way, just a few years ahead each product will have to show “additional benefit” to the patient, before reimbursment will be possible in all big pharma markets. Germany has started this year. And there will be no place for “Marketing data”, just hard facts and evidence based medicines.
But I think in a few years we’ll realize that this is hell, too, just the other side of it…
original industry insider
Keiner, I would also submit that equal benefit with less risk would meet criteria for reimbursement. Unfortunately Crestor is not a safer statin than Lipitor. In fact, Crestor has twice the incidence of adverse effects versus other statins. (see link)
http://www.druginjurylaw.com/Crestor-side-effects.html
Justice in MI
Keiner–Are you saying that reimbursement will depend on evidence of superior efficacy/lesser risk? By whose call? Hard to imagine that ever happening in the U.S., for a variety of reasons, not all bad (I agree).
What organization in Germany makes that call? On what basis does it know that the data used is evidence-based, and not reliant–at least in part–on suppressed, missing, or misrepresented data? Who serves and how are they chosen? How are individual/genetic differences factored in?
Or course, our tier approach (if you’re lucky enough to have insurance) already privileges some meds over others, and comparative efficacy or evidence-base are rarely the reason.
keiner
In Germany an organization hard to discribe (interface between physicians and (public) health insurers (www.g-ba.de) has the right to call a highly standardized document from each pharmaceutical company for each product (within 3 months from calling ;-) ). The level of scientific evidence to be provided in this document is comparable to Cochrane reviews or beyond. All interal and external studied have to be considered.
This document has to define the additional value of (new or old, no joke) medications against a reference standard (if there are several standards, it has to be shown against the cheapest alternative). If there is no additional value to the patient, the pharma company will have bad card for reimbursment talks with the health insurers :-)
They might end up for a totally new patent-pending product at the same level as several competitors with their out-of-patent low-budget generics.
No joke. Hard times for big pharma ahead…
keiner
PS: The organization finally assessing these “additional value” documents in practice (by outsourcing from the “g-ba”) is a highly controversial federal organisation, http://www.iqwig.de, which prepared exactly this type of documents (”additional value”), as now requested from the pharma companies.
But there was no legal basis to get these assessments into medical practice. This changed in the beginning of 2011..
So many “financial crisis” all over the world, nobody recognizes what’s really going on out there. ;-)
keiner
@OII:
Funny link to a lawfirm. This is the same way the cerivastatin story went for Bayer (”superstatin”), after they refused to sell ciprofloxacin with discount (or to lift patents), after these Antrax letters in US…
The bottomline was, that US docters use much to high doses in absolutely inadequate populations, although the labeling warned. In the end, patients paid the price… (and later on Bayer).
FTM
I see Baycol story differently.
Internal study showed did not measure up to Lipitor and much higher rhabdo rate. Study suppressed. Also info showing Baycol/fenofibrate very dangerous combo. Dr. HCP letter, but co. attempts to neuter it. Co. even put out word doing a study on a combo drug as apparent diversion from known dangers. At 8 mg. and an avalance of Medwatch reports, FDA finally acted.
FTM
gemfib, not fenofib
keiner
ALL statins at sufficiently high doses are dangerous with gemfibrozil, no exception. Just that cerivastatin was dosed at 0.2, 0.4, 0.8 mg, numbers docters consider to be VERY LOW, while doses of 200, 400, 800 mg are considered high (BIIIIG numbers). An so docters doses cerivastatin excessively high.
There are no safe drugs, only safe doctors…
That’s the way it is.
keiner
Here we go, that’s the way the stroy will go:
http://www.pharmatimes.com/Article/11-09-05/Lilly_Boehringer_delay_Trajenta_launch_in_Germany.aspx
FTM
ya, keiner, that was Bayer’s argument in court. In general, no one bought it.
Cover-up and and spinning label played roles.
It’s not about the drug. In this case, it was about company corruption. Doctors also got mugged.
keiner
In general, no one bought it.
http://www.amazon.com/All-Justice-Money-Can-Buy/dp/1607146304/ref=sr_1_1?ie=UTF8&qid=1315321046&sr=8-1
I read this with interest :-D
US mass torts and pharma trials have nothing to do with science or facts about drugs. ;-)