by JANE ALLIN
The year 2010 saw the reduction in the number of farms in the North American PMU industry dwindle to a mere 26 ranches housing approximately 40 horses each. This is a far cry from the once prolific industry that flourished in Manitoba, Saskatchewan and North Dakota where at the peak of its manufacture in 2003, 400 farms were in operation churning out gallon upon gallon of Pregnant Mares Urine to support the global HRT demand.
Given the health risks associated with conventional HRT therapy (i.e. Premarin®, Prempro®), which uses conjugated equine estrogens (CEEs) as the hormonal component, there has been a downturn in the market since the WHI (Women’s Health Initiative) estrogen-plus-progestin trial and estrogen-alone trial were both halted early (in July 2002 and February 2004 respectively) since results indicated that health risks of the conjugated equine estrogen and progestin exceeded benefits.
As WHI data has been analyzed, risks of blood clots, heart disease, ovarian cancer, and dementia have also been identified along with the initial findings of increased breast cancer risks. Experts, to this day, do not yet know whether lower-dose, shorter-term HRT reduces or eliminates these risks.
Nonetheless, rather than create safer and more humane alternatives, Pfizer and Wyeth, now a subsidiary of the leviathan pharmaceutical company, continue to fervently pursue the HRT market as the products reap great rewards in terms of profit margins. Despite the decrease in market demand for Premarin® global sales were up 23% to $261 million in 2010, driven not by increasing prescriptions but presumably by rising prices and non-prescription Internet sales.
However successful Premarin® is or was, there is a new kid on the block which, in a market still plagued with safety concerns, has an opportunity to restore market growth for hormonal replacement therapy (HRT). Yet to receive regulatory approval in the USA or elsewhere, the Phase III combination product, Aprela® has, in limited clinical trials, been shown to reduce the severity and frequency of several menopausal symptoms, including vasomotor symptoms and increased bone mineral density (BMD) values.
Aprela®, composed of the SERM (selective estrogen receptor modulator) Bazedoxifene and CEEs, has been sitting in limbo in the US as a result of issues with the osteoporosis component Bazedoxifene also known as Viviant® and Conbriza® in the EU. SERMs are compounds that bind with estrogen receptors and exhibit estrogen action in some tissues and anti-estrogen action in other tissues.
Although Bazedoxifene has been approved in the EU (2009), Spain and more recently Japan (2010) its approval by the FDA in NA has been postponed repeatedly due to complications of stroke and venous thrombotic events. Accordingly the delay for sanctioning Viviant® has had a significant effect on the roll out date for Aprela® in NA. However, this is obviously not the case for other global jurisdictions. In fact the approval and sales of Bazedoxifene are advancing rapidly in other parts of the world. Bazedoxifene will launch in Italy in the next few months and will be the only SERM on the Italian market. 
A recent blog by Jeff Berk, of BOLT International lends insight into Pfizer’s strategy and its quest to infiltrate the marketplace with yet another CEE-based product. BOLT International is an organization that specializes in pharmaceutical and healthcare market research, competitive intelligence, due diligence, horizon scanning, marketing, clinical trial reporting, technology/product assessment and finance. 
“Who is going to get to prescribe bazedoxifene? Probably the company will market that with gynecologists. So it will be a gynecologist’s drug. So this is going to happen. That the drug will be prescribed by gynecologists and will be mostly let’s say surrogate of estrogen………
“………….Most panelists are more enthusiastic about Aprela (bazedoxifene TSEC; the combination with low dose estrogen) than they are about Viviant. This is not driven by the SERM alone, as raloxifene is viewed as a better SERM. But the combination may offer physicians a safer way to prescribe estrogen for menopausal symptoms. One panelist said that Pfizer is filing the combination now, so we estimate that by ASBMR 2012 Aprela should launch in the US.”
Beck goes on to say:
“So the question there then becomes is this really the same thing as estrogen without progesterone? And the answer may be yes. And if it is estrogen without progesterone because the bazedoxifene is essentially doing what the progesterone would have done you may very well get moderate antifracture efficacy as well as some real benefits in terms of the miseries of menopausal symptoms. So while I don’t see it as the world’s greatest bone drug, it could if it turns out to be adequately safe and we won’t know that for a long time, it could turn out to be sort of estrogen without the problem….
“…… Estrogen still scares people and it may well be that even though it is estrogen together with bazedoxifene that the average patient is going to be scared to death. The patient who is terrified of taking estrogen who took it, who loved it, but is terrified of ever taking it again because everybody she knows has breast cancer may be equally terrified to touch something that has the word estrogen in it…….
“….Pfizer Wyeth was reluctant to introduce bazedoxifene in a marketplace that we thought by 2012 would have Raloxifene Teva, Teva’s SERM, but there is a bigger window. What I am hearing between the lines is the preferences for the US because SERMs haven’t had great penetration because they increase vasomotor symptoms to introduce tissue selective estrogen receptor complex; Premarin and bazedoxifene in the US. They are actually submitting an NDA right now, the FDA with the data.
“Yeah that has been a while coming also. I think the US will not see bazedoxifene alone but it will see TSEC (tissue selective estrogen complex).
So let’s assume that they get filed by ASBMR and put eight months onto it so some time in 2012 we should have bazedoxifene plus estrogen available. Right, yes.”
If 2012 is the actual launch date for Aprela® in the US then it can’t be far away for the rest of the world. Moreover, it seems Pfizer is now trying to circumvent the uncertainty regarding the safety issues of Bazedoxifene identified by clinical trials and backed up by the FDA with it’s NDA submission of the combination drug rather than Viviant® alone.
How is this possible and why would the addition of CEEs – acknowledged carcinogens – make this product a safe alternative?
If Aprela® is approved across the globe, Datamonitor predicts that should Pfizer invest in physician education and dispelling concerns over HRT among the general population, Aprela® will reach sales of US$207 million in the seven major markets (US, Japan, France, Germany, Italy, Spain, UK) in 2019. And this does not include Premarin® sales.
So this brings us back to the question of the PMU farms.
If sales are predicted to increase within the next few years or so, where will the PMU come from? Is it possible for a smattering of mares in NA to provide the quantities necessary to manufacture sufficient product to satisfy global markets? The amount of CCEs in Aprela® will be the same as that already sold in Pfizer’s Premarin® product. Pfizer’s argument for the decrease in North American PMU ranches is that they have made ground-breaking inroads into more efficiently extracting and concentrating the equine estrogens in PMU. But have they or is this simply more deception on Big Pharma’s part? After all, it would be par for the course.
International Fund for Horses has already reported on rumors of PMU farms emerging in places consistent with general acceptance of horse slaughter such as China, Kazakistan and Poland, and Pfizer’s attention to increasing sales in emerging markets outside of the US. There is little doubt that this is a well-defined strategy on their part to move away from the ever watchful eye of horse advocates in North America. In countries where cultural, political and legal values contrast our own so radically there will be no recriminations for them to answer to. How decidedly convenient for them.
“The trouble with lying and deceiving is that their efficiency depends entirely upon a clear notion of the truth that the liar and deceiver wish to hide. In this sense, truth, even if it does not prevail in public, possesses an ineradicable primacy over all falsehoods.” ~ Hannah Arendt
Out of sight; out of mind; deception in its finest form.