In February of this year Pfizer announced their intention to seek U.S. regulatory approval for the combined menopausal-osteoporosis drug Aprela®, a combination of Premarin® and bazedoxifene. Bazedoxifene is a Selective Estrogen Receptor Modulator or SERM also known as Viviant® specifically developed to help prevent postmenopausal osteoporosis.
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.
If and when approved, Aprela® will be offered as an alternative to Pfizer’s controversial hormone-replacement therapies – Prempro® and Premarin® – both associated with increased cancer and cardiovascular risks among countless other maladies. Aprela® is predicted to restore the HRT market with peak sales of approximately $1 billion if approved in 2013. Some speculate that approval in North America will be not be sanctioned given the delays in developmental stages and inherent risks associated with both components that comprise the new drug.
On February 17, 2012, just shortly before the Premarin® patent expired, Pfizer and Zhejiang Hisun Pharmaceutical, a leading pharmaceutical company in China, signed a framework agreement pursuant to an earlier announcement which would establish a joint venture to develop, manufacture and commercialize off-patent pharmaceuticals in China and global markets.
Ostensibly this was a direct consequence of Premarin’s patent expiration with the potential to drive brand sales over the long term and substantially boost overall sales give China’s large population.
Nearing the end of March the Int’l Fund for Horses revealed, via information procured from an inside source at a bulk powder conjugated estrogen manufacturing company in China, that PMU farms have been in operation in Northern China for the last 8 years with the company’s manufacturing site also in the same location.
This more or less coincides with the release of the WHI study citing the horrors associated with CEE-derived HRT. Well aware of the risks involved, 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.
On April 1, 2012 a large study was presented at a cancer conference in Chicago. The research involved roughly 60,000 nurses who participated in The Nurses’ Health Study. Data was analyzed from 1980 through 2008. Women who took both estrogen and progesterone (Prempro for example) had an 88 percent higher risk of breast cancer after 10 years on the treatment.
Those who took estrogen alone for at least a decade had a 22 percent increased risk of developing breast cancer. Those women who were exposed to just estrogen for more than 15 years had a 43 percent greater chance of being diagnosed with breast cancer.
Despite the continuing efforts of the medical profession and Big Pharma to reassure women that taking estrogen by itself, short term, to relieve symptoms will decrease the risk of breast cancer, the data continues to roll in against this reasoning. There's a continued increase in risk with longer durations of use and there does not appear to be a plateau.
In May results of a study conducted at Massachusetts General Hospital in Boston revealed that hormone replacement therapy taken by some women after menopause is linked with ulcerative colitis. It is a disease of the colon (large intestine) or rectum causing diarrhea, abdominal cramping and rectal bleeding. Data from nearly 109,000 women past menopause enrolled in the Nurses’ Health Study that began in 1976 indicate that those on hormone therapy had a 1.7 times higher risk of ulcerative colitis, compared to never-users.
Also in May Pfizer announced a restructuring of its estrogen extraction plant at Brandon, Manitoba calling for about 40 per cent fewer employees by the end of next year. Pfizer stated that it plans to cut about 50 of 130 positions at the plant “gradually through to the end of 2013. Apparently this layoff will not affect the PMU ranchers “for now”. Time will tell.
On the heels of the announcement that Pfizer would be downsizing their Brandon Manitoba estrogen extraction plant, in June the Int’l Fund for Horses learned, through direct correspondence, that certain companies seeking to get into the generic Premarin® market are looking to enter into contracts with PMU ranchers for the collection of pregnant mare’s urine ostensibly as Pfizer vacates them.
As much as the patent stifled the competition for such a long time, there is no doubt that during these years the technology for manufacture has been developed by other pharmaceutical companies awaiting the loss of patent protection.
Of course the lawsuits continue. Also in June the price tag Pfizer's Prempro® settlements was estimated.
The drugmaker has paid $896 million to wrap up about 60% of the patient lawsuits representing about 6,000 cases Pfizer has also set aside more money--$330 million--to cover the rest of its Prempro® liability for about 4,000 suits still outstanding. Total: $1.226 billion for 10,000 cases. The company also noted that the extra $330 million is just an estimate and may not cover all of the remaining 4,000 claims.
In July more deception by the medical profession surfaced. A coalition of leading medical groups has concluded that hormone-replacement therapy can be useful and safe for many women suffering from the symptoms of menopause.
The coalition includes 15 medical groups, including the North American Menopause Society, the American Society for Reproductive Medicine, the Endocrine Society and the American Academy of Family Physicians. The goal of the statement, released Monday, is to reassure women and doctors that hormone-replacement therapy (HRT) is acceptable and relatively safe for healthy, symptomatic, recently postmenopausal women,
With concerns about risks associated with conventional hormone replacement therapy manufactured from the urine of pregnant mares (i.e. Premarin®, Prempro®) Depomed Inc., a specialty pharmaceutical company headquartered in Newark, CA submitted a New Drug Application (NDA) to the U.S. FDA on July 31, 2012 for Serada™ – an extended time release formulation designed to provide women with prolonged relief of menopausal “hot flashes” with potential for reduced side effects.
Approximately one month later on August 29, 2012, Noven Pharmaceuticals announced that it had submitted a NDA for low-dose mesylate salt of paroxetine (LDMP) to the FDA also seeking approval for the treatment of vasomotor symptoms associated with menopause. LDMP is an investigational oral non-hormonal therapy specifically developed for the treatment of vasomotor symptoms due to menopause.
The FDA formally accepted the application for Serada™ on October 15, 2012 and established a Prescription Drug User Fee Act (PDUFA) action date of May 31, 2013. Similarly, the application for LDMP was also accepted with an assigned PDUFA action date of June 28, 2013. These dates represent the goal date for the completion of the FDA NDA review.
Hormone replacement therapy (HRT) manufactured from pregnant mare’s urine is currently the only FDA-approved single-agent therapy for the treatment of menopausal hot flashes. Such non-hormonal drugs as these would be a welcome reprieve for women and horses alike.
In October Martha Rosenberg long-time writer about the issues surrounding the Premarin® family of drugs penned another excellent article: “Will Women Have Short Memories About Hormone Replacement Therapy?” The question arises as to whether a new generation of women approaching menopause will lose sight of the HRT lessons of the 1970s and 2000’s. No doubt Big Pharma’s slick marketing tactics will try to sway this generation in favor of these carcinogenic drugs despite the risk. It has never stopped them before and the FDA still condones their sales.