UPDATE: Aprela approved by the FDA during last federal government shutdown under the name Duavee.
Written by JANE ALLIN
Pfizer’s recent announcement to seek U.S. regulatory approval for their combined menopausal-osteoporosis drug Aprela® is nothing short of an appalling money grab and a ruse to defer negative focus from their controversial hormone-replacement therapies – Prempro® and Premarin® – both associated with increased cancer and cardiovascular risks among countless other equally insidious maladies.
Some speculate that approval will be not be sanctioned given the delays in developmental stages and inherent risks associated with both components that comprise the new drug.
Aprela is a combination of Premarin® and bazedoxifene, a selective estrogen receptor modulator or SERM also known as Viviant® specifically developed to help prevent postmenopausal osteoporosis. Of particular note is that Viviant® has failed to receive approval from the FDA as a result of increased risks of stroke and thromboembolic events although it has been approved for use in other countries (i.e. EU and Japan) under different trade names.
Fortunately the delay in approving Viviant® has, until now, had a significant impact on the introduction of Aprela to the marketplace which was slated for 2008. Moreover, in 2010 Pfizer, announced the withdrawal of its new drug application (NDA) for Fablyn® another SERM specifically developed for the treatment of both osteoporosis and selected consequences of menopause. As with many other SERMs, Fablyn® has been shown to have significant side-effects which contraindicate widespread use. Is bazedozifene any different?
What if anything does this medication really offer other than continued abuse of pregnant mares and questionable efficacy as far as safety is concerned? Recall that conventional HRT was used for years without heed to negative and life-threatening side effects primarily as a result of the notion of menopause as a disease coupled with the idea that it is “normal” for females to succumb to breast, ovarian and endometrial cancers among other “female” issues. During those years, it seems, mitigating the discomfort of menopause prevailed over safety.
That all changed however with the eye-opening results of the WHI and the realization that conventional HRT as provided by Big Pharma, and at the mercy of the wombs of countless horses, is nothing more than a poisonous carcinogenic concoction of hormones alien to the human body. What makes anyone think that these same equine-derived biological hormones, disguised within more complex and questionable drugs with side effects of their own will safely provide a solution to a natural ageing process, common to women since the beginning of time?
But then again it is a dual acting drug that has been marketed as the panacea to the ever-ageing population; combating the woes of menopause and the risks of osteoporosis. Appealing indeed to kill two birds with one stone as the saying goes regardless of the presence of known carcinogens. Why must Pfizer continue to endorse Premarin®, present in the same quantities in this new drug with the pretty name, when there are no doubt natural or synthetic, potentially safer, alternatives? They simply continue to downplay the risks at the expense of the lives of both women and horses alike.
There is a reason why bazedoxifene has yet to be approved by the FDA and that is one of safety. And there is undeniably no question as to the harm conjugated equine estrogens (CEEs) contribute to the overall health of pre- and postmenopausal women. It is also interesting that Pfizer has opportunely eliminated the term “equine” from the description of these hormones and now refer to them as simply “conjugated estrogens”. Yet another ploy to distance the connection between the horse and the drug – Pfizer’s agenda is incredibly transparent. One need only look at their strategy of relocating the PMU farms away from North America.
In any case Pfizer claims that preliminary, and very limited, studies of Aprela® have not shown to prove deleterious to the overall health of women in terms of carcinogenic effects. In the same breath, the reservations in terms of safety continue for bazxedoxifene after longer-term studies (compared to Aprela®) continue to plague its approval by the FDA.
Moreover as is well recognized cancer typically takes years to develop. Even with lowered doses of CEEs over time, women have succumbed to death at the hands of Pfizer-Wyeth, subsidized with ghost written articles and overall cloak and dagger antics by Big Pharma in an attempt to champion unsafe drugs with the ultimate goal of reaping millions if not billions of dollars in profit.
Furthermore the fact that Aprela® contains the same dosage as Premarin® in a pill combined with a drug that has major side effects is disconcerting. Pfizer wants the population to believe that the two together are synergistic and negate the side effects of each other – a magic formula where two wrongs make a right. Given Pfizer’s reputation, let alone the whole of the pharmaceutical industry and its deception and greed, there is an element of trust categorically missing from the equation. Sadly the mares and foals will continue to suffer relentlessly.
Pfizer’s projected annual sales for HRT therapies – Premarin® and Aprela® – are over one billion USD by 2015 but some analysts predict it will be much lower (~$200 million) primarily as a result of the negative side effects associated with both drugs in combination with development delays and lack of FDA approval for bazedoxifene/ Viviant®. Regardless of what the actual profit margins will be this nonetheless represents a lot of urine from the PMU mares.
This becomes a dichotomy of sorts.
With the closing of many of the PMU farms beginning in the summer of 2010 with reportedly 26 ranches housing approximately 40 horses each and most recently the news of a North Dakota PMU ranch closure where many of these horses are at risk of shipping to slaughter, where will all of the pee required to manufacture these demon drugs come from? At the peak of manufacture in 2003, 400 farms were in operation churning our gallon upon gallon of pregnant mare’s urine. Pfizer wants us to believe that they have refined the process of CEE extraction from the urine such that much less is needed yet rumor has it that they have simply relocated the farms to foreign countries.
As to their rationalization Pfizer has indicated their interest in maintaining smaller farming ventures that would limit the amount of estrogen produced to 10,000 grams per contract. Some basic math taken from a 2010 iFH article will further reveal the ambiguity of this intriguing equation. See https://tuesdayshorse.wordpress.com/2010/05/26/the-rise-and-fall-of-the-pmu-industry/
If 25 farms each produce a total of 10,000 grams of conjugated equine estrogens (CEEs) this equates to a total harvest of 250,000 grams of CEE per annum. For the sake of simplicity, let’s assume that the average amount of CEE contained in a Premarin®-related product is 0.45 mg based on the mid-range of available dosages and presumably the most commonly prescribed measure since its introduction as a low-dose option in April 2003.
The total number of mg of CEEs produced per year under the new guidelines is given by:
Total grams CEEs/year = 250,000 grams CEEs/yr x 1,000 mg/gram
= 250,000,000 mg CEEs per year
Hence, the total number of single dosages available per year, assuming each dose is comprised of 0.45 mg can be determined as follows:
Total single dosages/year = 250,000,000 mg CEE per yr / 0.45 mg
= 555,555,555 single doses /yr
Since a typical HRT regimen is a single dose/tablet (tab) per day, the total number of prescriptions that will be available assuming the total number of farms are reduced to this level and limited to a 10,000 g contract, can be calculated as follows:
Total # prescriptions/yr = 555,555,555 tabs per yr / 365 tabs per yr [i.e. 1 tab/day]
= 1,522,070 prescriptions /yr
Interesting that only about 1.5 million prescriptions can be filled if this is the case particularly given that data from 2008 (Source: IMS Health) showed that upwards of 15 million prescriptions were filled by physicians that year, not including those available online without a doctor’s signature or other products containing the same (e.g. vaginal creams). It is unlikely that number has varied considerably since this time and sales of Aprela® no doubt, with its “safer” profile and double action efficacy, will exceed this globally.
Something is undeniably amiss.
Almost two years ago the International Fund for Horses reported on the rumors of PMU farms emerging in places consistent with general acceptance of horse slaughter such as China, Kazakhstan and Poland, as well as Pfizer’s attention to increasing sales in emerging markets outside of the US. It seems then we must resign ourselves to this sad fate for the mares and their foals; how else can Pfizer supply the current and projected global demand?
This brings us to the ever present plight of the horses.
What was and is today a brutal industry in the abysmal treatment of the pregnant mares and their foals here in North America will prove to be even more devastating for them in countries seemingly more accepting of animal abuse, horse slaughter and consumption of the meat of this heinous practice. While women can choose whether or not to engage a regimen of Premarin®-related therapy, unfortunately the mares and their foals are at the mercy of Pfizer and those who choose this unwarranted route to so-called “wellness”.
One thing is clear, as Pfizer slowly pulls the plug on the PMU industry here in North America the harsh reality is that this barbaric practice is not going away; it is simply moving house. Even with scientifically-based consensus that equine-derived estrogen therapy is almost certainly not a safe option for the relief of menopausal symptoms, Pfizer marches on at any and all costs.
Along with the announcement to seek approval for Aprela®, it seems Pfizer is ramping up new marketing strategies through the use of innovative training campaigns along with attractive new graphics and packaging in expectation that a new image will compel physicians to fill out more prescriptions. Designer drugs, just like a pair of jeans.
Disgraceful? You bet.
But the crusade against Pfizer/Wyeth and their despicable lack of empathy for both humans and animals alike is not over; we must now direct our energies across the globe – a much more difficult task, no doubt. Continued vigilance in the fight to shut down the PMU industry is the only thing that will save the mares and their innocent foals from the greed-driven and sinister hands of Big Pharma.
Pfizer, the snake in snake oil.
Jane Allin is Chief Research Analyst for the Int’l Fund for Horses and regular contributor to Tuesday’s Horse, primarily specializing in the Premarin Horses and Horse Racing issues. Jane dedicates numerous hours working for the welfare of horses and is the proud mother of two spoiled Golden Retrievers, Alex and Abby. A native Canadian, Jane has volunteered with the Int’l Fund for Horses since 2009.
© Int’l Fund for Horses