Tag: menopause

Daughters of Premarin®: The Generics

By JANE ALLIN

FURTHER to the reference of generics in the “Alternatives to Drugs Made with Pregnant Mare’s Urine”, I think a separate word on the availability of generic Premarin® and its daughter drugs is warranted to clear up any confusion for those seeking to avoid products manufactured from the urine of pregnant mares.

Premarin has a long and interesting history when it comes to FDA approval of generics, a history mired in the ruthless and bloodthirsty battle of Big Pharma patent wars.

Many years ago, in 1986, the effectiveness of Premarin®’s, and other short-term acting estrogens, ability to diminish bone loss associated with osteoporosis was granted approval by the FDA. What was once a drug that was prescribed for the relief of menopausal symptoms now became the panacea for a long-term chronic problem. [1]  And with this came a huge untapped market.

At this time there were certified generics that were interchangeable with Premarin®.  However because of the ramifications of long-term use, the science behind the drugs prevailed.

While Premarin® provided slow-release bioavailability, the generics were immediate release. This disparity in mode of release would turn into a long battle between the generic manufacturers, Wyeth-Ayerst and the FDA. [2]

To make a long story short, the outcome of detailed analysis showed that the bioavailability of generic versions was not equivalent to Premarin® and in 1991 the FDA withdrew approval of all ANDAs (Abbreviated New Drug Applications) proclaiming that none of the synthetics on the market could be considered generic versions of Premarin®. [3]

Because of the lucrative market potential, two generic manufacturers – Duramed and Barr – set out to develop products that solved the bioavailability problem and submitted ANDAs for FDA approval. Both met the requirements of adsorption efficiency however Wyeth had been conducting its own research and contested FDA approval on the grounds that the generic drug lacked one of the estrogens, called delta 8,9 (dehydroestrone sulfate), present in Premarin®.

Nevertheless, in 1994, the FDA unanimously ruled that delta 8,9 (dehydroestrone sulfate) was an impurity and not a required ingredient of a generic version.

Duramed applied for FDA approval of Cenestin in September 1995, and Barr followed the next July. [4]  

What happened next effectively blocked any competitor from manufacturing a generic Premarin®. Propaganda and political persuasion tactics were used to coerce the FDA and in 1995 Wyeth-Ayerst successfully petitioned the FDA to require the presence of delta 8,9-dehydroestrone in any generic version of Premarin®. [5]  Together with Wyeth-Ayerst’s patent on synthetic delta 8,9-dehydroestrone, this shut out the competitors.

Eventually Duramed filed a NDA (New Drug Application) for its synthetically derived estrogen Compound Cenestin which is still available on the market today along with a variety of other synthetic products, none of which contain pregnant mare’s urine.

Premarin® lost its patent in February 2012 and the patent for Prempro® held by Wyeth Pharmaceuticals, does not expire until early 2015. 

Despite Premarin’s® patent expiration there seems to be no interest in manufacturing a generic version from pregnant mare’s urine. [6]  In any case, it would be challenging for another pharmaceutical company to synthesize a medication that is similar enough to Premarin® to receive the approval of the FDA, similarly so for Prempro® as it contains the same natural conjugated equine estrogens as Premarin®.

The so-called Premarin generics are the lab-synthesized versions manufactured from plant sources not pregnant mare’s urine (see “Alternatives to Drugs Made with pregnant Mare’s urine). [7] 

As a reminder, these drugs carry with the same serious risks as the Premarin® family of drugs.

Some will say that generic Premarin® is available online without prescription, particularly from Canada. However be wary of any medications that tout themselves as being a safe generic version of Premarin®. Congressional testimony from the US FDA points out the dangers of inadequately regulated foreign Internet sites which have also become portals for unsafe and illegal drugs. This excerpt specifically targets Canadian generic websites: [8]

“A recent example illustrates some of the dangers associated with the purchase of prescription drugs from rogue pharmacy sites. Within the last six months, FDA has examined two web sites having identical web pages headlined “Canadian Generics” which were identified through spam e-mails sent to consumers.  FDA has purchased prescription drugs from both of these sites, and has found that these drugs and the manner in which they are sold pose potential threats to the health and safety of consumers.

There is at least one Canadian flag on every page of these sites, as well as the words “Canadian Generics.”  The web sites say, “Order Canadian to get the biggest discounts!”  Both of the URLs from which the orders were placed suggest the sites are located in, and operated out of, Canada. Despite these representations, however, we determined there is no evidence that the dispensers of the drugs or the drugs themselves are Canadian. The registrants, technical contacts, and billing contacts for both web sites have addresses in China.”

There is currently no therapeutically equivalent version of Premarin® available in the United States.  In other words, there is no approved generic for Premarin in the US.

The drug policies and generic approval practices in other countries may vary. What is a generic in one country may not be approved as one in another.

Fraudulent online pharmacies may attempt to sell an illegal generic version of Premarin®. These medications may be counterfeit and potentially unsafe.

If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. [9]

Consult Your Doctor

Always consult your doctor before embarking on any change in medication

_______________

[1]  http://pubs.acs.org/subscribe/archive/mdd/v03/i08/html/kling.html
[2]  Same as at 1.
[3]  Same as at 1.
[4]  http://www.sagepub.com/jowett5estudy/cases/77821_c2.pdf
[5]  Same as at 4.
[6]  http://www.drugs.com/availability/generic-premarin.html
[7]  http://www.horsefund.org/pmu-alternatives-to-cee-drugs.php
[8]  http://www.fda.gov/newsevents/testimony/ucm113635.htm
[9]  Same as at 6.

RELATED READING

The Quest for a Generic Premarin – A Bitter Pill to Swallow, By JANE ALLIN, Tuesday’s Horse, Nov. 14, 2014 »

Angelina Jolie and her choice of bio-identical hormone therapy

By JANE ALLIN

Posted on Tuesday’s Horse, March 31, 2015

A recent article in Health-TODAY.com – “Angelina Jolie’s ‘bio-identical’ therapy raises hormone questions” – challenges the safety of ‘bio-identical’ hormones versus conventional therapies including those of the Premarin family that contain conjugated equine estrogens (CEEs).

Biodentical Hormones Logo.

The article tends to dwell on the compounded versions of these so-called ‘bioidentical’ hormones rather than FDA approved versions when the focus should be directed to the actual safety profiles of any given HRT medications.

While the term ‘bio-identical’ is indeed unscientific terminology invented by marketing strategists to promote sales of these compounded hormones as the article clearly points out, it is by no means used exclusively in this context.

Yet this article, endorsed by the medical profession, hones in on compounding pharmacies and skirts the real issues of any of the available HRTs.

‘Bio-identical’ simply refers to laboratory synthesized hormones that are molecularly analogous to hormones such as estrogen and progestin produced in women’s bodies.

Bioidentical hormone therapy is often called “natural hormone therapy” because bioidentical hormones act similar to the hormones produced in the body.

But the word natural is confusing.

Pregnant mares’ urine is natural, but Premarin is not bioidentical, nor is Cenestin, which is made from plants, at least not to human estrogen.

Bioidentical estrogens and micronized progesterone are made into a range of products, many of which are FDA-approved and available with a prescription. Commercially available bioidentical estradiol comes in several forms, including pill, patch, cream, and various vaginal preparations. Similarly micronized progesterone comes in a capsule or as a vaginal gel. [1]

So ‘bio-identical’ hormones are not always compounded as this article would lead you to believe.

Moreover they have launched this histrionic dialogue on Jolie’s choice of combating menopausal symptoms without the slightest clue as to what she has opted for. Despite this they do acknowledge that she is likely using an FDA approved product, not a compounded version.

“We do not know whether Ms. Jolie is on an FDA-approved product, or a compounded one,” said Pauline M. Maki, president of the North American Menopause Society. “Given that she is using a patch, it is likely an FDA-approved form.”

“In fact, when it comes to the type of patch Jolie revealed she’s wearing, compounding pharmacies cannot legally make them, said Dr. Shira Miller, a Los Angeles holistic menopause and anti-aging physician.” [2]

So what’s the point?

While there is no question that credible scientific evidence to support claims made regarding the safety and efficacy of compounded bio-identicals is lacking, shouldn’t the medical community be questioning the safety of any FDA approved hormone medications – bio-identical or otherwise, not just compounded versions – which we know come with questionable profiles?

Instead it is the same old, same old rhetoric about FDA approved therapies and the “rigorous” testing these drugs undergo before approval that make them so much safer.

“I would argue safety from the FDA products [is] more robust, and they monitor adverse outcomes,” Starck added. “Experts assert bio-identicals are not any better or safer than FDA-approved hormones.” [3]

Big Pharma Puppets

I’m not sure that informed women would disagree with the fact that compounded bio-identicals are any more effective or safer but the greater question looms as to the safety of those that are FDA approved.

FDA Logo.

The article brushes this aside in an attempt to convince the audience that anything that requires a prescription in inevitably safer.

But what can you expect from the medical community? A throng of professionals who have been brainwashed by Big Pharma and the FDA.

The simple fact is that any type of synthetic hormones formulated in laboratories carry with them risks, particularly those manufactured from the urine of pregnant mares where the risks are significantly greater.

Even the innocuous sounding drugs such as Cenestin, that contains conjugated estrogens manufactured synthetically from plant material, have potential serious side effects similar to those associated with conjugate equine estrogens (e.g. blood clots, endometrial cancer, breast cancer, dementia, etc.)

While synthetics other than those containing CEEs carry with them the same or similar warnings associated with their use, it has been repeatedly cited in scientific literature that estrogens derived from pregnant mares’ urine pose a significantly greater risk due to the conspicuous fact that equine estrogens are foreign to humans but not horses.

GASP – what a concept.

“No auto mechanic in his right mind would replace worn parts in a Mercedes with new parts made for a Chevy. Unfortunately, many physicians (and pharmaceutical companies) seem to have less common sense than the auto mechanic when it comes to treating menopausal women.” [4]

There are three types of hormones produced in the human body — estradiol, estrone and estriol — all regulated by human enzymes and cofactors necessary to process these hormones when they occur in natural human proportions.

In humans these estrogens occur in an approximate ratio of; 7% estradiol; 3% estrone and; 90% estriol.

In contrast Premarin primarily consists of estrone (75-80%); equilin (6-15%); estradiol + two other equine estrogens (5-19%) plus quantities of other estrogens foreign to the human body.

First note the disparities between the concentrations of estrone and estradiol and of course the presence of the equine estrogens found exclusively in horses — clearly problematic in relation to the safety profile of these drugs.

Obviously the ratios of the common estrogens and the presence of equine estrogens can without doubt induce hormonal imbalances that can have far-reaching adverse effects on human hormonal regulation mechanisms.

Not only do these estrogens contribute to imbalances but they are also associated with increased risks for a variety of cancers.

A closer look renders CEE-derived HRT products even more sinister

Premarin® contains at least 10 estrogens that are the sulfate esters of the ring B saturated estrogens: estrone, 17beta-estradiol, 17alpha-estradiol, and the ring B unsaturated estrogens: equilin, 17beta-dihydroequilin, 17alpha-dihydroequilin, equilenin, 17beta-dihydroequilenin, 17alpha-dihydroequilenin, and delta-8-estrone. Bioassays and estrogen receptor binding studies indicate that all 10 estrogens are biologically active. Moreover, individual components, such as equilin sulfate, delta-8-estrone sulfate, 17beta-dihydroequilin sulfate and estrone sulfate, have potent estrogenic effects. Since all of the estrogens present in Premarin have estrogenic activity, the pharmacological effects of Premarin are a result of the sum of these individual activities. [5]

And:

As two leading reproductive physiologists point out, when women take Premarin, “Levels of [equilin] can remain elevated for 13 weeks or more post-treatment due to storage and slow release from adipose [fat] tissue. In addition, metabolism of equilin to equilenin and 17-hydroxyequilenin may contribute greatly to the estrogen stimulatory effect of [conjugated estrogen] therapy”. Another metabolite of equilin, 17-dihydroequlin has been found to be eight times more potent that equilin for inducing endometrial growth, a possible precursor to cancer.[6]

Additionally:

There has been recent interest in oestrogen metabolites because there are indications that they can be involved in the development of hormone-dependent tumours, e.g. breast cancer. Zhang et al. have shown that equilin metabolites have toxic properties with carcinogenic potential through the formation of quinones. A special carcinogenic risk factor may be the formation of semiquinone-adducts with DNA.[7]

But there is more:

In women, a recent study has evaluated the potential of HRT to induce DNA damage in peripheral blood leukocytes of postmenopausal women using the comet assay (Ozcagli et al. 2005). Significant increases in DNA damage were observed among women receiving 0.625 mg/day conjugated equine estrogens or conjugated equine estrogens plus medroxyprogesterone acetate as compared to the control group that had never received HRT. Finally, the excessive production of ROS in breast cancer tissue has been linked to metastasis of tumors in women with breast cancer (Malins et al. 1996; Malins et al. 2006; Karihtala and Soini 2007; Benz and Yau 2008). These and other data provide a mechanism of estrogen-linked tumor initiation/promotion by redox cycling of estrogen metabolites generating ROS, which damage DNA.[8]

ROS stands for “Reactive Oxygen Species”.

Cancer Cell Cllipart

Various carcinogens, such as CEEs, may partly exert the effect of oxygen derived species (e.g. superoxide radical) by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis.

Cancer is ugly, so are CEEs

Sadly, most conventional physicians, in addition to the self-serving Pfizer, are quick to rationalize the cancer and other risks of ingesting horse estrogens in favor of preventing age-related heart attacks or strokes rather than the undeniable life-threatening dangers proven to be associated with CEE-containing HRT.

Clearly not all HRT is created equally

Yet this article, in its single-minded evaluation of compounded bio-identicals, downplays or simply fails to acknowledge the risks associated with other forms of HRT, particularly the Premarin family of drugs – blindly claiming that FDA approved prescription drugs are safer.

The risk of any hormonal product depends on its hormonal components and how it is manufactured. FDA approved bio-identicals do not contain the myriad estrogens in Premarin – estrogens primarily foreign substances that clearly carry with them greater risks than those endogenous to the human body.

I’ll take bets that even these compounded bio-identicals are safer than Premarin. In fact there have been a limited number of studies that support this opinion.

However what is paramount to any of this discussion is the disturbing notion that this concoction of CEEs — a regularly prescribed drug for menopausal women, not a life-saving one — is still on the market given that it is a known carcinogen as proclaimed by the World Health Organization and the National Toxicology Program.

I doubt that any such drug would survive if it was prescribed for the other gender.

Thank you Ms Jolie

And last, but not least, thank you Angelina Jolie for your courage and your willingness to share your story so that others may learn from it.

And a special thank you from the horses for not choosing Premarin® and its vile sister drugs including the recent Duavee.

_______

[1] http://www.health.harvard.edu/womens-health/what-are-bioidentical-hormones
[2] http://www.today.com/health/angelina-jolies-bio-identical-therapy-spurs-hormone-questions-2D80569287
[3] Same as 2.
[4] http://www.smart-publications.com/articles/dont-let-your-doctor-give-you-horse-urine-for-menopause
[5] http://www.ncbi.nlm.nih.gov/pubmed/9421201
[6] Same as 4.
[7] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014957/
[8] http://goo.gl/xuB7lW

Featured Image: Angelina Jolie. Hong Kong Tatler.

Pregnant Mare’s Urine Images

CHINA

PMU farm in Xinyuan County

PMU Farm in Xinyuan County, China (2012). Slide 1.
PMU Farm in Xinyuan County, China (2012). Slide 2.
PMU Farm in Xinyuan County, China (2012). Slide 3.
PMU Farm in Xinyuan County, China (2012). Slide 4.
PMU Farm in Xinyuan County, China (2012). Slide 5.
PMU Farm in Xinyuan County, China (2012). Slide 6.
PMU Farm in Xinyuan County, China (2012). Slide 7.
PMU Farm in Xinyuan County, China (2012). Slide 8.
Chinese version of Premarin cream.

N. AMERICA

There are no longer any PMU farms in the U.S. However, there are a reported 19 “pee farms” remaining in Canada although NAERIC’s website states:

“There are 24 family-owned equine ranches that are members of NAERIC and contracted by Pfizer to collect pregnant mares’ urine (PMU). These equine ranches are located in the Canadian provinces of Manitoba (19) and Saskatchewan (5). All ranches are within reasonable proximity to Pfizer, in Brandon, Manitoba, where the initial PMU processing occurs”.

While there are no images available to the public of what the inside of these farms look like that we can find, here are some of the byproduct horses.

Belgian horses awaiting shipment to Japan from Canada to Japan for slaughter. Live horses exported to Japan are killed for a specific foodstuff: a kind of specialty sashimi called basashi.
Horses loaded and waiting on the tarmac in Canada for live transport to Japan for slaughter for human consumption. Canadian Horse Defence Coalition image.
Activist photo taken at the Calgary Airport in 2017 show four draft horses per crate, a practice which was banned by the CFIA five years ago. Canadian Horse Defence Coalition image.
A PMU mare and her foal.

Vintage Images

Sanitized picture released by the USDA.
A “Pee Line”, Canada. Brenda Hunter photo.
PMU Farm. Winnipeg, Canada.
PMU Farm. N. America.
PMU Farm. N. America.

Featured Image: Grey Draft Horse. Horse Illustrated.

THF 2019 Logo. ©The Horse Fund.

Premarin Timeline 2014

Duavee enters the marketplace

Pfizer’s latest menopausal drug Duavee, the combination menopausal-osteoporosis drug, comprised of conjugated equine estrogens (Premarin) and bazedoxifene (Selective Estrogen-Receptor Modulator) was approved by the FDA on Oct 3, 2013 and was available to the marketplace in the first quarter of 2014.

However the FDA approval was not without provisions. Due to the heightened risk of endometrial hyperplasia, potentially a precursor to endometrial cancer, Wyeth/Pfizer is required to conduct a post marketing pharmacokinetic trial to evaluate the effect of conjugated equine estrogens and bazedoxifene on imminent changes in endometrial tissues within the selected cohort of non-obese and obese postmenopausal women. See http://goo.gl/mFpmON»

In effect the FDA has granted them permission to sell this concoction to unsuspecting women despite the undeniable concern that there is an increased risk of endometrial cancer. The final report from Wyeth/Pfizer is to be submitted by 04/2015 – an entire year and a half after its approval.

Pfizer had a lackluster first quarter, and the continued profit decline, accompanied by a lack of groundbreaking drugs on the horizon, disappointed investors. Despite the fact that Duavee took years to get to market along with biased studies, inexcusable side effects, questionable data and the fact that the FDA has yet to approve bazedoxifene as a stand-alone drug, Pfizer is pinning its hopes on Duavee to pick up the slack.

Pre-and post-market availability of Duavee, Pfizer ramped up an aggressive direct to consumer campaign and boosted its marketing efforts that continued throughout the year, not only for its new drug but also Premarin tablets and vaginal cream. Similarly medical doctors were plied with the benefits of Premarin and Duavee and encouraged to prescribe it to their patients – particularly Duavee – the so-called “safer” of the two drugs.

In late May 2013, Pfizer followed several other pharmaceutical companies in their quest to extend the period of their New Chemical Entity (NCE) exclusivity for their Fixed-Dose Combination drug Duavee to 5-years from the 3 years they were granted when it was approved on October 2013. To date the FDA has denied all petitions. The reasons for Pfizer’s fight for a 2-year extension are unclear – bazedoxifene has yet to be granted approval by the FDA nor is there a generic version of Premarin on the market.

Pfizer continues to fight its legal battles in the courtroom over the carcinogenic effects of the Premarin family of drugs. Of note is a class action lawsuit pending in Canada that has the potential of proving this to be true in a high number of cases, revealing important facts and figures previously uncovered – the body of evidence to date overwhelmingly points to a causal connection between the use of Premplus and the development of invasive breast cancer in women.

In a Canadian study conducted by the Canadian Cancer Society, its top epidemiologist alleges that popular menopause drugs made in part from estrogen found in the urine of pregnant horses have caused breast cancer in thousands of Canadian women. Wyeth, now wholly owned by Pfizer continues to deny this of course.

A blow to horse advocates and those opposed to the use of CEE-containing hormone therapies came in October of this year with the news that Kim Cattrall, star of Sex and the City, teamed up with Pfizer to promote Duavee in a campaign called “Tune into Menopause”. This, despite the fact that Cattrall is not a Duavee patient, has the potential to influence and encourage many women to take this drug.

On October 27, 2014 the combination conjugated equine estrogen / bazedoxifene venom, to be sold under the name of Duavive, was recommended for approval by the European Medicines Agency (EMA) so it is only a matter of time before it is available in Europe.

After the launch of Duavee in the first quarter of the year Pfizer reports that the sales of their combo drug have grown to more than 5,000 prescriptions per month. Sales projection for 2014 is approximately 100 million USD, estimated to double by the year 2020. See http://consensus.druganalyst.com/Pfizer/Duavee/#

Last but by no means least, the horses. In North America the NAERIC (North American Equine Information Council) website lists the number of mares on the PMU farms as 2,000.

NOTE: It is well known however that the primary production of CEEs for the manufacture of the Premarin family of drugs now takes place overseas in Asian locations (China, possibly India). As for the exact number of farms and mares on the pee lines this has yet to be confirmed. Needless to say, they must far out-number those left here in North America. How long will it be before the ranches here disappear? —Jane Allin.

Pfizer turns the sex talk toward 50-ish women with a menopause awareness push

Anyone who’s watched a Viagra commercial knows that Pfizer ($PFE) isn’t too embarrassed to talk about sex. Anyone who’s run across Pfizer’s “Get Old” campaign knows it doesn’t shy away from aging, either. Now, the drug giant is going equal opportunity on the sex-and-aging talk, and “Desperate Housewives” actress Brenda Strong has the dialogue.

With its latest menopause awareness campaign, Pfizer is taking a break from hot flashes and night sweats. Instead, it’s focusing on some lesser-known effects of menopause, namely painful intercourse and vaginal atrophy. They’re not terms tossed around at your average dinner party, and Pfizer’s campaign capitalizes on the uncomfortable.

Aptly titled “Let’s Talk About Change,” the campaign has launched with a YouTube video titled “The Other Talk.” In one scene, Strong’s character engages her daughter in the birds-and-bees conversation so often lampooned in Hollywood comedies. Predictably, said daughter closes the door in her mother’s face. But then the tables are turned. Strong’s character finds herself in an awkward conversation with her mother–about menopause and its effects on her mother’s sex life.

Pfizer’s point is that women need to talk to someone about these little-known effects of menopause. If not their mothers, then perhaps their partners–and most importantly for Pfizer, their doctors. “It’s our hope that ‘The Other Talk’ video will prompt new dialogue about the symptoms of post-menopause,” Strong says in a Pfizer release. “The video is funny, but has an important message–more women should be talking about these changes and taking action to help find relief. Women should not have to suffer in silence.”

If women did ask their doctors–and if the conversation goes as Pfizer might hope–women would not only hear about symptoms but also get information about the company’s products for those very symptoms.

To give a nudge, the “Let’s Talk” home page includes a link to Pfizer’s Estring brand website. A vaginal ring that releases estrogen over a 90-day period, Estring is approved specifically to treat any unpleasant menopausal changes in the vagina and is designed to act locally rather than systemically. Among its rivals is Osphena, approved in February 2013; Shionogi specifically touts it as a nonestrogen treatment for vaginal changes around menopause.

Estring is just one in Pfizer’s lineup of hormonal treatments for menopausal side effects. Its Premarin line of products, acquired along with Wyeth in 2009, still generates blockbuster-level sales, with $768 million for the first 9 months of 2014. Pfizer knows well about potential side effects of hormonal therapy in menopausal women; it paid $1.2 billion in 2012 to settle lawsuits over its Prempro drug and its links to breast cancer.

In October 2013, the company won approval for Duavee, which pairs estrogen with bazedoxifene, an ingredient designed to temper some of the safety risks that can accompany solo therapy with estrogen. Approved to treat hot flashes and to help prevent postmenopausal osteoporosis, the drug goes up against a new nonhormonal pill for hot flashes, Brisdelle, and a variety of hormone-based osteoporosis fighters, including Eli Lilly’s ($LLY) Evista. END

Source: FiercePharma »

Pfizer is stuck with a hot flash med that took years to get to market

DUAVEE
Project name: conjugated estrogens/bazedoxifene
Disease: Moderate-to-severe vasomotor symptoms
Peak sales estimate: $200 million
Approved: Oct. 3
Companies: Pfizer and Ligand Pharmaceuticals

THE SCOOP
Pfizer ($PFE) already had treatments for menopausal women in its quiver when it got approval for Duavee, a drug it acquired in its buyout of Wyeth in 2009. In fact, what it refers to as its Premarin family of products, which also came with Wyeth, generated more than $1 billion in sales last year. But while many women would like to find something to treat hot flashes, they have been scared off by a decade of discussion over the risk of developing breast cancer after taking hormones for the symptoms.

Duavee is approved for moderate-to-severe hot flashes related to menopause in women who haven’t had a hysterectomy as well as for prevention of postmenopausal osteoporosis. It differs from other hormonal treatments by being the first to combine estrogen with the estrogen agonist/antagonist bazedoxifene, which reduces the risk of endometrial hyperplasia. Some experts think the combo may mean it will have fewer of the increased cancer and other risks that have plagued earlier drugs in the category, including Prempro and Premarin. The company certainly understands the potential downside those risks pose; it has reported that litigation tied to these risks in its hormone products have cost it about $1.6 billion over the years.

Pfizer touts the drug as a hormone therapy with few of the side effects associated with similar treatments, but it has a risk history of its own. Originally known as Aprela, Wyeth started work on it in 1999, as part of a program with Ligand ($LGND). They had hoped for a 2007 approval, but FDA concerns over health risks kept pushing that opportunity further into the future. Still, some experts say Duavee may not carry the same safety concerns about long-term use of estrogen. Doctors who treat women with menopause know their patients are ready for a treatment option.

Duavee, however, is not the only alternative approved this year, and its competitor does not rely on hormones for its benefits. Brisdelle from Noven Therapeutics, a unit of Hisamitsu Pharmaceutical, is the first nonhormonal treatment for hot flashes. What it does contain is paroxetine, the same ingredient found in the popular antidepressant and antianxiety drug Paxil. Paroxetine carries a boxed warning about the risk of suicide associated with its use in children and young adults, and so the drug carries that as a boxed warning.

Pfizer could have given up on Duavee. Some analysts did, surmising it would never get to the market. That makes it difficult to gauge its potential earnings power. There have been forecasts that it could generate $200 million. But given that sales of the Premarin family of drugs top $1 billion and Eli Lilly’s ($LLY) Evista for prevention of postmenopausal osteoporosis also reaches blockbuster status, it is hard to say. — Eric Palmer. END

Source: FierceBiotech »

The Horses

Premarin, Prempro, Premphase and Duavee are examples of the Premarin family of drugs which are made with the the estrogen rich urine of pregnant mares.

In the ‘pregnant mare urine’ (PMU) industry, horses are repeatedly impregnated so their urine can be collected and made into hormone replacement products . Some of the foals are rescued , but most are simply slaughtered and seen as a byproduct (much like male calves in the dairy industry).

There are alternatives. Talk to your doctor. Visit your local pharmacy. There are prescription free over-the-counter treatments for hot flashes, vaginal dryness and other menopausal symptoms. Thank you.

More Timeline

1686-1998 | 2001-2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019

THF 2019 Logo. ©The Horse Fund.

Premarin Timeline 2019

JANUARY 2019

FDA denies Pfizer Petition asking for new method of assessing Premarin generics

The FDA has denied a citizen petition from Pfizer calling on the agency to use the company’s method for assessing sameness in generics for its estrogen drug Premarin (conjugated “equine” estrogens).

Pfizer had appealed to the FDA to force sponsors of generics for Premarin to use the “Pfizer method” for assessing sameness rather than the method recommended in FDA draft guidance.

Pfizer claimed that the FDA’s December 2014 draft guidance for establishing sameness is “fundamentally flawed”. Additionally claiming that not only does it lack a critical level of sensitivity on API (Active Pharmaceutical Ingredient) steroidal composition, but also it does not account for all classes of components in the API or the non-steroidal components.

They maintained that guidance should instead use the “Pfizer Method” that the company developed at the FDA’s request and with their input, which permits a determination of sameness between a proposed generic for the company’s drug Premarin and the reference drug based upon the mixture as a whole, while allowing a comparison across all categories of components making up the API.

APRIL 2019

Bijuva launched for moderate to severe hot flashes in menopause

TherapeuticsMD announced the launch of Bijuva (estradiol and progesterone) capsules for use in women with a uterus for the treatment of moderate to severe vasomotor symptoms (hot flashes) due to menopause. It initially received approval from the Food and Drug Administration (FDA) in October 2018.

Bijuva is the first bio-identical hormone therapy that combines estradiol and progesterone in a single capsule. Compared with synthetic hormone products, the estradiol and progesterone found in Bijuva are structurally identical to the hormones naturally circulating in the woman’s body.

Bijvua carries a Boxed Warning regarding cardiovascular disorders, breast cancer, endometrial cancer, and probable dementia. Breast tenderness, headache, vaginal bleeding, vaginal discharge, and pelvic pain were the most common adverse reactions associated with Bijuva.

JUNE 2019

PMU Ranchers feel pinch as cuts announced

Pfizer Canada’s cuts to pregnant mares’ urine production will force four Manitoba ranches and one Saskatchewan ranch out of the industry.

The reduction affects three ranches in southwestern Manitoba, one in the Interlake region of Manitoba, and one in Saskatchewan. Of those five, three producers raised registered Quarter horses, one bred purebred Percherons, and one raised sport horses.

Pfizer has initiated a review of its inventory management and determined they are able to satisfy market demand by working with fewer ranchers.

The latest reduction leaves 19 producers still involved in PMU production in Manitoba and Saskatchewan, with most ranches located in southwestern Manitoba, four each in south-central Manitoba and southeastern Saskatchewan and one in the Interlake.

JULY 2019

Pfizer’s Wyeth loses bid to duck hormone-therapy lawsuit

Pfizer Inc’s Wyeth unit must face a class action alleging that the drugmaker misled California women by downplaying risks including breast cancer associated with its hormone-replacement therapy products, a federal judge has ruled.

U.S. District Judge John Houston in San Diego on Monday ruled the plaintiffs presented sufficient evidence for a jury to decide whether Wyeth’s alleged misrepresentations caused women to buy Prempro, Premarin and Premphase.

To read the full story on Westlaw Practitioner Insights, click here: bit.ly/2FOpbRU »

New Book — Flash Count Diary: Menopause and the Vindication of Natural Life, by Darcy Steinke

“What orcas can teach humans about menopause and matriarchs“, A new book argues for a sea change in the way our culture views older women. 

Her research unearthed a long history of dubious “cures,” from transfusions of dog’s blood to vinegar sponge baths to putting a magnet in your underpants. All of which, she says, seem a little less strange once you realize that the most popular hormone replacement treatment, Premarin, is made from the urine of pregnant horses. Source: Crosscut »

AUGUST 2019

Hormone therapy during menopause raises breast cancer risk for years, study finds

New analysis adds to the evidence that many women who take hormone therapy during menopause are more likely to develop breast cancer — and remain at higher risk of cancer for more than a decade after they stop taking the drugs. 

The study, in the Lancet, looked at data from dozens of studies, including long-term data on more than 100,000 women who developed breast cancer after menopause. The longer women took the medicine, the more likely they were to develop breast cancer. Experts say the findings could shape how women and their health care providers decide how to manage symptoms of menopause.

For years, research has suggested a potential link between MHT and an increased risk of breast cancer.  But there wasn’t much information on whether that risk persisted, or how it differed based on the type of MHT a woman took. So, an international group of researchers pulled together data from dozens of studies — published and unpublished — to examine the issue more closely. 

The researchers found that compared with women who never used MHT, women who did had a significantly higher risk of developing invasive breast cancer. Also, the longer women used MHT, the greater their risk of breast cancer. 

OCTOBER 2019

Premarin sales figures continue to deline

The Premarin family of hormone replacement products was the 11th best seller in 2018 at $832 million, a decline of 14.8 percent. Sales in the first six months of 2019 were $361 million, 10 percent less than in same period of 2018.

Third quarter sales of Premarin (conjugated estrogens tablets, USP) family — $182 million, down 11%.

Data as of 12.27.19

About Premarin Horses

Premarin®, Prempro®, Premphase® and Duavee® are examples of the Premarin® family of drugs which are made with the the estrogen rich urine of pregnant mares.

In the ‘pregnant mare urine’ (PMU) industry, horses are repeatedly impregnated so their urine can be collected and made into hormone replacement products. Some of the foals are rescued , but most are simply slaughtered and seen as a byproduct (much like male calves in the dairy industry).

There are many alternatives.

Talk to your doctor. Visit your local pharmacy. There are prescription free over-the-counter treatments for hot flashes, vaginal dryness and other menopausal symptoms. Thank you.

More Premarin Timelines

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Premarin Timeline 2018

JULY 2018

In an article entitled, “Top 25 Pharma & BioPharma“, ContractPharma reports:

In 2018, Pfizer reported revenues of $53,647 billion, an increase of two percent. Premarin sales delivered $832 million to that total, with sales down -15%. END

OCTOBER 2018

In an article entitled, “Menopausal Hot Flashes Market is Rising to a Valuation of US$ 5,284.1 Mn in 2023,” OnlineNewsGuru.com reports:

Transparency Market Research has published a new market report titled, “Menopausal Hot Flashes Market — Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2015 – 2023.”

According to the report, the global menopausal hot flashes market was valued at US$3.77 bn in 2014 and is projected to expand at a CAGR of 3.7% from 2015 to 2023 to reach US$5.28 bn by 2023.

Hot flashes are the most common vasomotor symptom of menopause complications. The usual symptoms include sudden sensation of intense warmth spreading over body lasting for several minutes leading to sweating, red flush, and palpitations.

Hot flashes may occur during the day or at night (also known as night sweats). The intensity of hot flashes vary from woman to woman depending on several physiochemical factors. It may be mild, moderate and troublesome, or severe and debilitating.

Hormone replacement therapy (HRT) has been considered as gold standard for the treatment of menopausal hot flashes. However, long term HRT has an increased risk of breast cancer and risk associated with increasing age such as stroke, blood clots, and other health related problems.

Other therapies include intake of vitamin E supplements and anti-depressants along with various complementary therapies.

In the U.S. and other developed countries approximately 70% of menopausal women suffer from hot flashes that can last for several years. According to a publication by Harvard Medical School, on average, hot flashes can last for about 7 years to 11 years.

NOVEMBER 2018

In an article entitled, “Pfizer Is Weighing Sale of $2 Billion-Women’s Health Portfolio“, Bloomberg reports:

•  U.S. drugmaker is gauging interest from potential buyers
•  Suitors likely to include private equity firms and drugmakers

Pfizer Inc. is reviewing options including a sale of its women’s health portfolio as the U.S. pharmaceutical giant seeks to focus on developing treatments with higher growth potential, according to people with knowledge of the matter.

The drugmaker is working with financial advisers to gauge the interest of potential buyers, the people said, asking not to be identified because the deliberations are private. A sale of the division, which has annual sales of roughly $1.2 billion, could fetch about $2 billion and draw bids from both private equity firms and rival pharmaceutical companies, they said.

A spokeswoman for Pfizer said the drugmaker declined to comment on speculation. No final decision has been reached and the company may yet decide to retain the assets, which include menopause treatments such as Premarin, Prempro and Premphase, the people said.

For more on Pfizer’s likely strategy under its new CEO, read this.

A divestment of the business would mean that Pfizer, which last month narrowed its full-year forecast amid manufacturing challenges within the business that makes its older medicines, is joining Allergan Plc and Teva Pharmaceutical Industries Ltd. in selling or winding down women’s health lines and shifting resources to other parts of their portfolios.

Allergan Chief Executive Officer Brent Saunders, who has been seeking to sell the firm’s women’s health and antibiotics divisions, this week said the offers so far have been below what the assets are worth. Last year, Teva opted to sell its women’s health division in separate transactions for about $2.5 billion as it raced to pay down debt. END.

THE HORSES

Premarin, Prempro, Premphase and Duavee are examples of the Premarin family of drugs which are made with the the estrogen rich urine of pregnant mares.

In the ‘pregnant mare urine’ (PMU) industry, horses are repeatedly impregnated so their urine can be collected and made into hormone replacement products . Some of the foals are rescued , but most are simply slaughtered and seen as a byproduct (much like male calves in the dairy industry).

There are alternatives. Talk to your doctor. Visit your local pharmacy. There are prescription free over-the-counter treatments for hot flashes, vaginal dryness and other menopausal symptoms. Thank you.

RELATED READING

Premarin, doctors and conjugated equine estrogens, Tuesday’s Horse, The Horse Fund (Oct. 8, 2018) »

1686-1998 | 2001-2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019

THF 2019 Logo. ©The Horse Fund.