November 2011 Archives
Today marks the generic availability of Pfizer's Lipitor, the blockbuster drug to beat all blockbuster drugs.Duff Wilson of the NYT lays out how Pfizer is leveraging its short-term losses (for instance, it will get 70% of generic maker Watson's profits).
And Forbes's Matthew Herper gets nostalgic for the era of the widely prescribed money maker ("Why There Will Never Be Another Drug Like Lipitor"). Specifically he provides a concise history of Lipitor's rise and plateau; but he unfortunately omits one of the most interesting and important points of the early Lipitor campaign.
When first approved by the FDA in 1996, Lipitor was only indicated to reduce LDL cholesterol; it had not been shown to prevent clinical vascular events like its 4 existing statin competitors at the time. Nevertheless, trial data showed that Lipitor reduced LDL cholesterol by a relatively greater percentage than the other statins. And because clinicians believed (and still do) that LDL cholesterol is directly linked to the risk of vascular events, Pfizer was able to leverage this belief into ever-escalating sales during the next several years without having data to show that Lipitor actually reduced the risk of vascular events.* Clinicians made the a-to-b-to-c connection with prescription-writing alacrity.
Oh BTW, the generic name of Lipitor: atorvastatin.
* Lipitor wasn't approved by the FDA for this indication until 2004.
Delayed update (12/10/11): In an intriguing NEJM Perspective piece, Jackevicius et al expect that atorvastatin will "dominate" the statin market as a result of switching from generic simvastatin and branded Crestor. Specifically, in 3 years, they expect the market share of atorvastatin to reach 44%. They also estimate, on the basis of experience with simvastatin (which went generic in 2006), that the price of generic atorvastatin will be about 50% of the price of branded Lipitor, after the 6-month exclusivity period ends for the first generic manufacturer.
The projected overall cost savings by 2014, owing to the generic availability of atorvastatin: $4.5 billion annually; when factoring in the aging of the population, add another $30 million. These projections assume the "rapid availability and timely uptake of generic atorvastatin," which may be delayed thanks to industry maneuvers between Pfizer and generic drug makers (which are designed to limit competition). Pfizer is also reportedly planning to ask the FDA to approve an OTC version of Lipitor at some unspecified date.
The intriguing "Do Nothing" option for reducing the country's $15-trillion deficit ostensibly includes a passive stance toward a looming cut to physicians' Medicare reimbursement on January 1. The ever-escalating SGR-defined cut, which has been stayed numerous times by Congress over the years, now exceeds a practice-killing 27%. Primary care physician Don Klitgaard in Iowa, interviewed by the Associated Press, predicts along with the rest of us that "there's going to be a temporary fix, because the health care system is going to implode without it." But an unidentified "senior Washington lobbyist" warns, "It's entirely possible given past performance that Congress misses the deadline." Compromise solutions are reportedly being entertained; they are painful, but not necessarily draconian, for physicians.SGR = sustainable growth rate.
Image of Westall's Sword of Damocles (1812) from Wikipedia. Meh: not a perfect analogy but close enough.
Loosely based on the life of Austrian Johann Kastenberger, The Robber (2010) is the semi-true story of a talented marathon runner, bank robber, and evidently incurable adrenaline junkie. We know what the ending of this tautly edited, highly kinetic tale must be; we just don't know how it will end.
And probably rightly so, given a number of issues.- The Harvard press release is terribly (and irresponsibly) overdramatic, emphasizing the "endocrine-disrupting" effect of bisphenol A (which is only documented in laboratory animals, to my knowledge) and the >1200% increase in urinary BPA after consuming canned soup (Progresso) for 5 days. There is no mention of absolute numbers in the attention-grabbing press release, just the astonishing percentage jump.
- The JAMA report, available here (courtesy of JunkScience.com), is actually published as a letter and not a more stringently peer-reviewed article.
- JunkScience.com takes the letter authors to task for not distinguishing between the urinary measurement of BPA (which is evidently not possible or very difficult) and that of a quickly produced metabolite. BPA is evidently rapidly processed in the body, and its "biologically inactive" metabolite (not BPA per se) was actually measured in urine, says JunkScience.com (the blog further claims that at least some of the authors should have known or do know this fact).
- While the percentage increase of mean urinary BPA values among canned-soup eaters is very impressive, we're talking about differences in MICROGRAMS PER LITER: 1.1 mcg/L after 5 days of fresh-soup consumption vs 20.8 mcg/L after 5 days of canned-soup consumption, for a difference of 19.7 mcg/L.*
- The urinary spike in BPA (or its metabolite) was probably transient, and the authors themselves acknowledge, "The effect of such intermittent elevations in urinary BPA concentration is unknown."
* In the updated National Health and Nutrition Examination Survey, levels of BPA were detected in all subjects older than 6 years of age. Geometric means were approximately 2 mcg/L, but levels rose to 20 mcg/L (or thereabouts) in the 95th-percentile groups.
Image of can of Progresso vegetable minestrone soup from progresso.com.
The Nature News Blog and Retraction Watch provide the ongoing, head-torquing narrative of Judy Mikovits, the dubious or embattled (depending on your viewpoint) XMRV-CFS researcher who was fired in September from the Whittemore Peterson Institute in Reno, Nevada. The latest news: Mikovits was arrested last Friday in California (as a fugitive from Nevada, from what I can tell) for allegedly stealing property—eg, laboratory notebooks—from the Institute.
And while the jig certainly appears to be up for Mikovits regarding the validity of her past scientific claims about XMRV and chronic fatigue syndrome or a future career in legitimate science, to hold her without bail (especially while, elsewhere, an alleged serial pedophile is allowed out on $100,000 and no monitoring) seems terribly draconian and patently unfair.
And while the jig certainly appears to be up for Mikovits regarding the validity of her past scientific claims about XMRV and chronic fatigue syndrome or a future career in legitimate science, to hold her without bail (especially while, elsewhere, an alleged serial pedophile is allowed out on $100,000 and no monitoring) seems terribly draconian and patently unfair.
The Square (2006): Modern noir Down Under. A philandering contractor's attempt to steal money for his lover escalates into a ridiculous series of coverup crimes. As the contractor, Australian actor David Roberts effects perfect, clueless ineptitude. We scoff at and feel the pain.
Geron is dumping (or seeking a partnership for) its stem-cell development program, according to a company press release from November 14. The stated reason: Geron wants to focus on its "first-class" oncology programs, which are not beyond the phase 2 stage of development, in "the current environment of capital scarcity and uncertain economic condition." So Geron is closing its "GRNOPC1 trial for spinal cord injury to further enrollment, although it will continue to follow all enrolled patients, accruing data and updating [the] FDA and the medical community on their progress." As of July, only 4 patients had been enrolled in the landmark and highly publicized trial, in which "GRNOPC1 has been well tolerated with no serious adverse events," according to Geron.
Geron's exit from clinical hESC investigation leaves Advanced Cell Technology as the only company, to my knowledge, that is actively engaged in clinical trials of human embryonic stem cells (specifically in cases of Stardgardt's disease and dry age-related macular degeneration [AMD]).
Besides oligodendrocyte hESCs (GRNOPC1), Geron is/was developing cardiomyocyte, pancreatic islet cell, dendritic cell, and chrondrocyte hESCs.
Transverse section of the thoracic spinal cord from Gray's Anatomy (1918).
The cryptically titled Bubble (2005): While watching this largely improvised and amateur-acted story of jealousy and murder, set among employees of a rural latex-doll factory, one wonders why all of Stephen Soderbergh's movies can't be this completely mesmerizing.
Forbes's Matthew Herper on Bill Gates on vaccines and pharma: There's sufficient ink for undeniably venerable ideas and acts, but an "unimpressed" Gates disparages Novartis's Gleevac, a molecule that has completely revolutionized the treatment of CML.
“There’s always this divergence between what’s financially attractive and what has dramatic profit and the number of life years that you really save...Do the math on [Gleevac] versus, says, preventing Parkinson’s or preventing Alzheimer’s. It’s in a different universe."
On Friday, the FDA approved Xarelto (generic name, rivaroxaban) for the prevention of stroke in patients with nonvalvular a-fib.* Approval of the direct factor Xa inhibitor, a product of Janssen Ortho (essentially JNJ) and Bayer Healthcare AG, was based on the mammoth-sized (N > 14,000) ROCKET-AF trial, in which Xarelto was found to be noninferior (ie, comparable) to warfarin for the prevention of stroke and other systemic embolic events in patients with nonvalvular a-fib and other stroke risks (mean CHADS2 score = 3.5).
Xarelto is the second anticoagulant to seriously compete with the old-as-dirt warfarin for the prevention of stroke in patients with a-fib. In October of last year, the FDA approved Boehringer Ingelheim's Pradaxa (dabigatran), a direct thrombin inhibitor. Neither medication requires the usually cumbersome protime monitoring, but Pradaxa, unlike Xarelto, was shown to be superior (at the 150-mg BID dosage) to warfarin for the prevention of stroke in a similar patient population.
Other important differences between Xarelto and Pradaxa are 1) the package insert for the former contains a so-called black-box warning (against the risks of thrombosis after drug discontinuation and spinal/epidural hematoma); and 2) Xarelto is taken once a day, unlike the twice-daily Pradaxa.
Beyond superior-versus-noninferiority claims, potential drug-related risks, and any convenience of dosing, a distinction between Xarelto and Pradaxa may emerge with respect to pricing. According to destinationrx, a month's supply of Xarelto costs $218.70 (~$7.30 per pill or day).** A month's supply of Pradaxa (60, 150-mg pills) will set you back $236.20 (~$7.87 per day). Much of the cost distinction between these 2 drugs, however, will probably depend on how formularies classify the drugs and exact prescription co-pays on health-plan members. Branded warfarin (ie, Coumadin) is, of course, a fraction of these costs, and the price of generic warfarin (which some cardiologists are loathe to prescribe owing to the unpredictability of protimes) is even lower still.
* As well as for the prevention of deep vein thrombosis (DVT).
** 10 mg daily is the dosage for DVT prophylaxis; for the prevention of stroke in patients without renal dysfunction, the recommended dosage is 20 mg per day.
Xarelto is the second anticoagulant to seriously compete with the old-as-dirt warfarin for the prevention of stroke in patients with a-fib. In October of last year, the FDA approved Boehringer Ingelheim's Pradaxa (dabigatran), a direct thrombin inhibitor. Neither medication requires the usually cumbersome protime monitoring, but Pradaxa, unlike Xarelto, was shown to be superior (at the 150-mg BID dosage) to warfarin for the prevention of stroke in a similar patient population.
Other important differences between Xarelto and Pradaxa are 1) the package insert for the former contains a so-called black-box warning (against the risks of thrombosis after drug discontinuation and spinal/epidural hematoma); and 2) Xarelto is taken once a day, unlike the twice-daily Pradaxa.
Beyond superior-versus-noninferiority claims, potential drug-related risks, and any convenience of dosing, a distinction between Xarelto and Pradaxa may emerge with respect to pricing. According to destinationrx, a month's supply of Xarelto costs $218.70 (~$7.30 per pill or day).** A month's supply of Pradaxa (60, 150-mg pills) will set you back $236.20 (~$7.87 per day). Much of the cost distinction between these 2 drugs, however, will probably depend on how formularies classify the drugs and exact prescription co-pays on health-plan members. Branded warfarin (ie, Coumadin) is, of course, a fraction of these costs, and the price of generic warfarin (which some cardiologists are loathe to prescribe owing to the unpredictability of protimes) is even lower still.
* As well as for the prevention of deep vein thrombosis (DVT).
** 10 mg daily is the dosage for DVT prophylaxis; for the prevention of stroke in patients without renal dysfunction, the recommended dosage is 20 mg per day.
I have to say that the most astonishing finding from President Obama's most recent routine physical examination is not that he's smoke-free or that his LDL fell with presumptive dietary changes or that he even got a PSA test but that he has 20/20 vision, near and far, without correction. Who the hell doesn't have to wear glasses for something after the age of 50? Photo of a glassless #44, from http://www.whitehouse.gov/about/presidents/barackobama.
