AMAG snaps up rights to new med Intrarosa to compete with Pfizer’s Premarin® vaginal cream

Tracy Staton reporting for FiercePharma.com writes as follows.

AMAG Pharmaceuticals Logo

Caslon Quote Left BlackAMAG Pharmaceuticals has big ambitions for its women’s health business, so it’s snapped up the rights to a new med, Intrarosa, to beef up that portfolio.

The company plans to tout Intrarosa’s safety profile to set it apart from established estrogen-based treatments such as Pfizer’s Premarin cream and Estring vaginal ring. The AMAG drug, which contains the hormone precursor prasterone, has a “similar efficacy profile,” CMO Julie Krop said this week. “[F]rom an efficacy standpoint, I don’t see that there is particularly differentiating advantage,” Krop said. “It’s really on the safety side”.

The company clearly sees big potential for Intrarosa. AMAG will pay Endoceutics $50 million up front, plus 600,000 shares of newly issued common stock, which closed Tuesday at $22.65. Follow-up sales milestones add up to $45 million if Intrarosa surpasses $300 million in sales over time.

AMAG says it’s adding those 150 reps to its current team of 100, who now focus on its preterm labor drug Makena and cord blood registry (CBR). For now, the new salespeople will exclusively handle Intrarosa, a non-estrogen treatment for vaginal pain during intercourse, which often affects post-menopausal women”.

"Premarin Vaginal Cream could result in more comfortable sex, uterine cancer, heart disease, heart attacks, stroke, dementia, blood clots or breast cancer."
“Premarin Vaginal Cream could result in more comfortable sex, uterine cancer, heart disease, heart attacks, stroke, dementia, blood clots or breast cancer.” Click to be taken to source article.

NASDAQ, in its press release on the licensing and introduction of Intrarosa states:

Caslon Quote Left BlackUnlike conventional pharmacological estrogen-containing medications, Intrarosa does not carry a boxed safety warning in its label.

Intrarosa enters an existing billion dollar-plus market for intravaginal prescription therapies that treat VVA symptoms. There are an estimated 64 million post-menopausal women in the U.S., and as many as 32 million women suffer from VVA symptoms.

VVA, or vulvar and vaginal atrophy, causes pain during intercourse (dyspareunia), a common symptom of menopause”.

Jane Allin, horse advocate and expert on drugs made with pregnant mare’s urine such as Premarin® cream which is also prescribed for dyspareunia, states:

“This drug is a steroid — prasterone — of which estrogen is a metabolite so carries with it the same risks as other estrogen substitutes for Premarin® (i.e. the use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer).

“So basically it’s just another form of estrogen that isn’t derived from horse pee. Safer but still has risks associated with estrogen.

“It would be nice if the pharmaceutical companies could come up with something that isn’t a steroid/estrogen. But that’s all they seem to know — and because it’s easy”.

Is this good news for the mares and foals used and cast off by the Premarin® industry?

“Intrarosa may cut into Pfizer’s Premarin® vaginal cream profits some but I doubt it will ever be enough that Pfizer would discontinue its sale”, states Vivian Farrell of The Horse Fund, “which is the only way the success of this new drug could help the horses used by the Premarin® industry in N. America.

“The popularity of Intrarosa may spare a few mares and foals along the way but it doesn’t appear it will spare women from the potential risk of breast cancer”.

“Where the largest threat to horses used and cast off by the PMU drug industry in terms of numbers is of course China where the copycat Premarin® cream they are manufacturing themselves is being marketed to untold millions of women”.

Packaging for Premarin like vaginal cream in China.
Packaging for Premarin like vaginal cream in China.

SOURCES

• “AMAG to hire 150 new sales reps to tout newly licensed women’s health med Intrarosa”, by Tracy Staton, FiercePharma.com, Feb 15, 2017.

• “FDA approves Intrarosa for postmenopausal women experiencing pain during sex”, FDA News Release, Nov 17, 2016.

Drugs.com Prasterone page.

FDA.gov Intrarosa label (pdf, 1p).

PREMARIN® HORSES

Premstoppers campaign, The Horse Fund website »

Premarin Horses Year in Review 2016, The Horse Fund, Tuesday’s Horse »

Premarin Horses: How many does it take to make a billion dollars? Part 3

Newest Member of the Premarin Family ― Duavee

Premarin foals.
Premarin foals.

How will this new drug impact profits and inevitably the PMU mares and their foals?

DUAVEE®, the Premarin® ― bazedoxifene combination therapy for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis in women who have not undergone hysterectomy was FDA-approved in October 2013 amid speculation regarding its safety profile and Pfizer/Wyeth’s lengthy struggle to gain approval.

Pfizer anticipates that DUAVEE® will be available in the U.S. in the first quarter of 2014.

This is the first approval of DUAVEE® in any country worldwide ― an approval of a combination drug with the component bazedoxifene yet to receive FDA approval on its own ― its approval is valid only in combination with Premarin®, at least in the US ― a conundrum in itself and worthy of further debate.

Some market analysts estimate DUAVEE®’s peak sales to reach $200 million (USD)/annum. [1]

DUAVEE® will be sold as a combination of 0.45 mg CEEs / 20 mg bazedoxifene however no pricing information is available yet as Pfizer has yet to launch it. If it sells for the same average cost per dose as Premarin® ― roughly $3.50 ― the number of mares, in addition to those currently on the pee lines, can be approximated.

Number of doses = Total Sales ($) / Cost per dose ($)
= $200,000,000 / $3.50/dose
= 57,142,857 doses
Total mg required = 57,142,857 doses x 0.45 mg/dose
= 25,714,286 mg
Number of mares = Total mg required / # of mg per mare
= 25,714,286 mg / 9466 mg/mare
= 2,716 mares

However all may not be lost on this new drug.

Despite the fact that Pfizer re-labeled this combination formula as innovative with an improved safety profile over conventional HRT 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 anticipating a FDA approval in 2007 however it took 6 more years for the FDA to finally put its rubber stamp on it all the while citing concerns over health risks.

With the still lingering fear of developing cancers from CEE-derived HRT and the fact that there are other best-seller osteoporosis drugs currently on the market ― for example Evista® from Eli Lily which generated $1 billion last year as well and its generic to be introduced within the month ― DUAVEE® may not become the block-buster Wyeth/Pfizer once thought.

Particularly encouraging is that inside information reveals that even Pfizer is vacillating on the roll-out of this drug.

The veil of controversy over safety efficacy and its long and tortuous road to FDA approval seems to have cooled the hype associated with its introduction to the market. In fact speculation has it that Pfizer may never put this drug on the market – a Godsend to the horses and women alike.

Comments made by Pfizer employees on a public forum reveal a decidedly different picture from the one painted by Pfizer-proper. Here are a few interesting and illuminating remarks.

    Look into why this drug has taken so long throughout R&D phases. Wyeth Women’s Health talked about this drug coming to market by 2005.”

    Just wait until the recall. This drug will make your uterus collapse.”

    It’s the biggest joke at Pfizer. Enormous amounts of money being spent for what will be the biggest failed launch since Exubera.”

    Bingo! The cost to promote this DuaDog far exceeds the profitability for the first five years. Any CSO could sell this thing for a better ROI. It’s not rocket science but simple math. Launch is seriously being questioned and could become a no go at any moment.”

    This product is a DOG! I hear that there is debate internally as to whether or not to even launch.”

    DUAVEE: Dropped Uterus And Vaginal Equine Estrogen”.

Shareholders also understand and do not want to bear the brunt of more lawsuits, nor do the innocent women and their families. It is obvious that few have faith in the safety profile of this drug or its marketability ― two risky drugs and limited clinical data makes for a bad recipe.

It is time to stop this madness.

Big Pharma ― rotten to the core ― deception, fraud, kickbacks, price-setting, bribery and illegal sales activities ― anything to keep their profits rolling in. They will stop at nothing to expand their profit base, even if it means harming or killing countless innocents, humans and animals alike.

God bless the mares and their foals and whatever fate awaits them for they are undeniably the persecuted innocents ― without voice or choice they suffer at the hands of greed and merciless degenerates with stilted vision who fail to comprehend the difference between right and wrong ― a capitalist system where underlying principles are lost to a delinquent world that worships money.

    Where in this wide world can men find nobility without pride,
    Friendship without envy, or beauty without vanity?
    Here, where grace is laced with power and strength tempered by gentleness.
    He serves without servility, he has force without enmity.
    There is nothing so powerful, nothing less violent.
    There is nothing so quick, nothing more patient.
    Our pioneers were borne on his back,
    Our history is his industry.
    We are his heirs and he is our inheritance…
    The horse
    .’

    ― ROBERT DUNCAN

END
__________
[1] http://www.fiercebiotech.com/special-reports/duavee-pfizer-stuck-hot-flash-med-took-years-get-market

Links to All Parts of this Report

PART 1: Introduction (A billion dollars ― lots of zeros)
PART 2: Every Figure Tells a Story (Calculations and Result)
PART 3: Newest Member of the Premarin Family ― Duavee (Approved by FDA October 2013, originally submitted under the name Aprela)

Pfizer to cut jobs at Manitoba PMU plant

Canadian Flag

Pharma giant says decision won’t affect its PMU ranchers

Byproduct foals from Premarin industry in slaughter feedlot.
A group of foals cast off by the PMU industry rescued Lifesavers Wild Horse Rescue.

Alberta Farm Express reports:

Drugmaker Pfizer’s restructuring of its estrogen extraction plant at Brandon, Man[itoba] calls for about 40 per cent fewer employees by the end of next year.

The company processes conjugated estrogen from pregnant mares’ urine (PMU) at Brandon to make the hormone replacement therapy Premarin, used to treat menopausal symptoms in women.

Pfizer said Tuesday it plans to cut about 50 of 130 positions at the plant “gradually through to the end of 2013.”

This layoff will not affect PMU ranchers for now. Even if it did, do not be fooled. The Premarin horse issue is not dead. Far from it.

As Jane Allin of the Int’l Fund for Horses points out in her peerless article, “Pfizer consigns PMU horses to killing fields of Asia“:

If anyone believes that the downsizing of the PMU industry here in North America is advantageous for the mares and foals who suffer at the hands of Big Pharma, they are sadly mistaken”.

Sadly mistaken indeed.

Allin open our eyes further:

While it is true that immediately following the release of the WHI study, citing the horrors associated with CEE-derived HRT, there was a precipitous drop in sales of Premarin® and Prempro®, some of that market was reclaimed in time via reduced dosage recommendations, aggressive marketing strategies, price increases and the wide availability of these drugs without prescriptions through Internet sales.

What no one realized at the time was that Wyeth had probably begun to move their PMU facilities prior to or just after the damning results of the WHI were released to the public.

A simple Internet search shows that several pharmaceutical-based companies in mainland China and India produce bulk conjugated estrogens in powder form. Interestingly enough, or perhaps clearly enough, Wyeth/Pfizer is and has been a customer for several years. Whether their procurements are limited to conjugated estrogens is unknown. But really, who else would purchase these products in such quantities without a vested interest in them?

In fact, according to information we procured from an inside source from one such company, PMU farms have been in operation in Northern China for the last 8 years. The company’s manufacturing site is also in the same general location.

WHAT YOU CAN DO

— Send our Dear Physician Letter to the OB/GYN’s in your area, particularly to the one you are consulting yourself, asking them not to prescribe the Premarin family of drugs. Learn more here >>

— Send our flyer to Pfizer asking them to develop an alternative to the Premarin family of drugs using new technologies that do not involve the use of pregnant mare’s urine. Learn more here >>

— Say no if your doctor tries to prescribe Premarin and Prempro.

— Learn why we must end the use of pregnant mare’s urine in drugs.

— Find alternatives to Premarin.

— Share this with the women in your life.

Thank you.

Wyeth wins, horses lose, in the Premarin® drug sales sweepstakes

Written by JANE ALLIN
Research Analyst | Int’l Fund for Horses

Thin Gray Line

Since the introduction of Premarin in 1942, much controversy has followed the lucrative market monopoly of the world’s first conjugated equine estrogen therapy for the treatment of postmenopausal women.

Historically, the number of PMU farms, sequestered mares and by-product foals steadily rose until the early 1990’s at which time a precipitous increase was observed (Figure 1). The escalation in the number of PMU farms appeared to coincide with the widespread compliance of physicians to prescribe Premarin® based on a powerful sales pitch by Wyeth that gave doctors and women alike the impression that every woman should be treated at menopause for declining estrogen levels and in particular the escalated risk of developing osteoporosis.

This marketing agenda not only falsely concluded that aging and menopause are diseases requiring treatment but also failed to admonish the inherent dangers associated with HRT. As far back as the mid-1970’s there was damaging evidence that the use of HRT was linked to cancer.

Figure 1.  Historical trend of PMU farms, mares and foals – Manitoba Canada
Figure 1. Historical trend of PMU farms, mares and foals – Manitoba Canada. Source: Government of Manitoba (1)

Apart from the burgeoning sales of Premarin® and then the inception of Prempro® in 1995, by the early 1990’s there was growing evidence about the risks associated with HRT. Meanwhile the Woman’s Health Initiative (WHI) was launched in 1991 with the objective of conducting medical research about health issues in menopausal women. These clinical randomized controlled trials were designed to test the effectiveness of postmenopausal HRT on heart disease, fractures and breast and colorectal cancer.

Until the time the first results of the WHI study were released in 2001, sales of the Premarin® family of drugs not only flourished but Wyeth gained a further foothold in the control of the marketplace when the FDA rejected an application for a generic brand of its blockbuster drug Premarin®. Both the FDA and Wyeth-Ayerst wanted the public to believe it was in their best interest to protect and safeguard but in reality it was motivated by scores of lobbyists, fraught with conflicts of interest, and epitomized by surreptitious political manipulation.

In fact, in the 1990s Premarin® became the most frequently dispensed drug in the US and by 1997 had become Wyeth-Ayerst’s first brand to reach $1 billion dollars in sales.

By 2001, news of the first results of the WHI hit both physicians and Wall Street alike and Wyeth-Ayerst’s epic family of HRT drugs nosedived in terms of company shares and market value. However, it wasn’t until the US government abruptly ended the WHI in 2002 citing the increased risk of cancers and cardiac complications that sales and use of the drugs by postmenopausal women plummeted.

As clearly illustrated in Figure 1, a steep decline in the number of PMU farms and producing mares was observed shortly after these events in response to the decreased demand of Premarin® and related CEE drugs. Although this may seem to have been a blessing to the suffering mares and their foals, sadly, the vast majority of the mares no longer required to “perform” were sent to slaughter along with their foals whether alive or still in the womb. Albeit lower numbers, the industry still thrives today and the suffering continues.

So where has that left Wyeth, now a subsidiary of Pzifer, the largest drug company in the world?

A closer look at the sales of Premarin® and projected sales of both Premarin® and their soon to be released Aprela conveys a malevolent tale of greed and depravity.

Data taken from a Wyeth Annual Product Sales summary clearly show the drop in profits from Premarin® from 2003 to 2004 that parallels the steep decline in the number of PMU mares as indicated in Figure 1. However, from 2004 and beyond sales increased slightly until 2006 and then remain relatively stable despite the fact that there were further declines in the number of PMU mares over the same period of time. Figure 2 shows the actual and estimated sales from 2003 to 2015 for both Premarin® and Aprela.

Actual and predicted sales of Premarin® and Aprela
Figure 2. Actual and predicted sales of Premarin® and Aprela. Source: JP MORGAN US Major Pharma 2010 Outlook (2)

What is alarming is that the sales profits appear to be unaffected while at the same time both prescriptions for the Premarin® family of drugs and the number of PMU farms and mares have declined dramatically since 2003 (Figures 3 and 4 respectively).

Figure 3.  Prescriptions of Wyeth’s HRT issued by physicians 2001-2008. Source: IMS Health The New York Times
Figure 3. Prescriptions of Wyeth’s HRT issued by physicians 2001-2008. Source: IMS Health The New York Times (3)
Figure 4.  Total estimated PMU mares 2003-2007. Source: NAERIC, Government of Manitoba, Government of Alberta
Figure 4. Total estimated PMU mares 2003-2007. Source: NAERIC, Government of Manitoba, Government of Alberta (4)

In fact, there was a decrease of approximately 80% in the number of prescriptions issued by physicians from 2001 to 2008 with a corresponding decrease of about 88% in the number of mares from 2003 to 2007 (estimated from current number of PMU farms and Manitoba/Alberta data). Somewhat confounding may be the prescription data since Premarin® is now available over the Internet without a prescription and so may not reflect the actual demand. However, more importantly, the number of producing mares divulges the underlying ambiguity.

A simple calculation of the profits generated per PMU mare from 2003 to 2007 will shock you (Figure 5).

Figure 5.  USD sales generated per PMU mare 2003-2007. Source: JP MORGAN US Major Pharma 2010 Outlook, NAERIC, Gov. of Manitoba, Gov. of Alberta
Figure 5. USD sales generated per PMU mare 2003-2007. Source: JP MORGAN US Major Pharma 2010 Outlook, NAERIC, Gov. of Manitoba, Gov. of Alberta (5)

In 2003, it appears that a single PMU mare generated about 25,000 USD per annum in profits for Wyeth, yet by 2006 and 2007 that same mare was worth in excess of 150,000 USD –- that is a sixfold increase in a mere five years. It is hard to envision a mare ramping up urine and estrogen production to sustain these sales figures.

Instead it is simply a case of Economics 101; Supply and Demand. At least that’s what Wyeth wants the consumer to believe. Unfortunately there is a major flaw in their argument since the overall demand for the Premarin® family of drugs has in fact decreased over time due to the inherent risks of cancer and cardiovascular complications associated with HRT (Figure 3).

While, it is true that the supply of CEEs has decreased, presumably in response to decreased demand, Wyeth has had no other option than to increase the price of its carcinogenic therapies to sustain profit levels.

A CTV news release in June of 2009 documents the scandalous agenda of Big Pharma and its continuing predisposition to gouging the consumer. From April to June of 2009, a month’s supply of Premarin® increased an astonishing 800 per cent, from about 14 cents a pill to about $1.24 a pill. (6)

Unfortunately, when a patent expires there is no limit to what a company can charge for its drugs since its pricing doesn’t come under the jurisdiction of the federal government’s Patented Medicine Review Board (Canada).

Wyeth defends its position with the following gibberish:

The new price is reflective of current costs, including higher manufacturing and ingredient costs and a long-term, steady reduction in the consumption of the product, increasing the per-dose and per-patient cost significantly.”

“Wyeth Pharmaceuticals says its decision “was based on extensive research, including discussions with stakeholders, physicians and patients, and reflects the value Premarin brings to Canadian women. Key inputs from that research showed that Canadian physicians and women wanted us to continue to offer the product.

“While we understand this is undesirable for some patients, the only other option was to remove the product from the market, and many Canadian women continue to rely on this unique product.” (7)

Oh really? As if they would take it off the market. I hardly think so! After all, it is still accruing 1 billion USD a year and with the predicted arrival of Aprela in 2011, which also contains CEEs, Wyeth has estimated that figure to increase even further (Figure 2).

It is simply criminal what Big Pharma is allowed to get away with. Not only is it permissible to manufacture and deceptively market carcinogens, endangering the lives of women and horses alike, it is obviously clear that they can do so at any cost to the consumer. It is no secret that the FDA and the pharmaceutical companies are entwined in a sinister conspiracy, but what about the democratic governments of the United States and Canada?

The pharmaceutical industry is hardly a model of free enterprise. Of course, it is free to manufacture what drugs it sees fit to expand its portfolio of block-busters, many of which are merely slight modifications to existing compounds. It is also free to price them as high as the market will bear. Ultimately however, it is entirely reliant on monopolies delivered to them courtesy of the government, for example patents and FDA endorsed marketing rights.

There has never been a better time to stop this madness.

© Int’l Fund for Horses

Thin Gray Line

LINKS TO SOURCES

(1) Government of Manitoba — http://www.gov.mb.ca/agriculture/statistics/yearbook2006/past_trends_other_farm_products.pdf

(2) JP MORGAN US Major Pharma 2010 Outlook — http://www.docstoc.com/docs/21388254/JP-MORGAN-US-Major-Pharma-2010-Outlook/

(3) IMS Health The New York Times — http://www.nytimes.com/2009/08/05/health/research/05ghost.html

(4) a. NAERIC, b. Government of Manitoba, c. Government of Alberta —
a. http://www.naeric.org/; b. http://www.gov.mb.ca/agriculture/statistics/yearbook2006/past_trends_other_farm_products.pdf; and c. http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/sdd10294/$FILE/table67&68.pdf

(5) a. JP MORGAN US Major Pharma 2010 Outlook, b. NAERIC, c. Gov. of Manitoba, d. Gov. of Alberta —
a. http://www.naeric.org/; b. http://www.gov.mb.ca/agriculture/statistics/yearbook2006/past_trends_other_farm_products.pdf; c. http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/sdd10294/$FILE/table67&68.pdf; d. http://www.docstoc.com/docs/21388254/JP-MORGAN-US-Major-Pharma-2010-Outlook/

(6) http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090603/premarin_090603/20090603/

(7) See above.

Thin Gray Line

© Int’l Fund for Horses