Will FDA Approve New Menopause Drug Aprela?
A form of hormone therapy is absolutely necessary with some women as their quality of life is severely hampered by their menopausal symptoms. The frustration is that there is insufficient detail on the inherent risks of taking products like PremPro or Premarin. We are told the risk of uterine cancer is a fairly low percentage but its still no comfort to those women taking these drugs in order to combat their menopausal symptoms. Perhaps this new menopause drug Aprela could offer a better outlook for women, if it gets FDA approval.
However, repeated delays in developing the new drug, Aprela, have raised questions about its potential. Some analysts and doctors question whether regulators will approve it, and Aprela's market potential could be limited by continued safety concerns about hormone-based drugs.
The New York-based drug maker expects to submit Aprela for Food and Drug Administration approval sometime this year, according to Olivier Brandicourt, president and general manager of Pfizer's primary-care unit. He discussed Aprela in an interview earlier this month.
Mr. Brandicourt said the drug has the potential to reduce menopausal symptoms such as hot flashes and to prevent bone-thinning osteoporosis, but with a better safety and tolerability profile than older hormone-replacement therapies.
"We think this is a market which is unsatisfied … and if you can bring a hormone therapy which doesn't have the traditional side effects, we can actually lead that marketplace," Mr. Brandicourt told reporters at a November meeting.
Many women stopped using hormone-replacement therapies after a large government study, the Women's Health Initiative, raised safety concerns a decade ago.
PremPro, which Pfizer acquired with its purchase of Wyeth in 2009, was shown to increase risk of breast cancer. A similar drug, Premarin, has been tied to increased risk of uterine cancer, and both drugs have been linked to risks for stroke and certain blood clots. Pfizer has set aside more than $800 million to cover previous and potential settlements and judgments for lawsuits alleging injuries caused by hormone-replacement therapies.
Aprela contains an active ingredient found in the older drugs, known as conjugated estrogens, which are derived from the urine of pregnant horses.
But Aprela combines conjugated estrogens in a single pill with another drug, bazedoxifene, that may mitigate the risks of conjugated estrogens alone.
Bazedoxifene is a selective estrogen receptor modulator, or SERM, the same category as Eli Lilly & Co.'s Evista, which is approved to prevent and treat osteoporosis. A SERM is designed to provide the benefits of estrogen while mitigating the negative effects of estrogen such as increased risk of uterine cancer. Pfizer, via Wyeth, licensed bazedoxifene from Ligand Pharmaceuticals Inc.
"It is a great concept and so far the clinical trials have shown benefit over risk," said JoAnn Pinkerton, a professor of obstetrics and gynecology at the University of Virginia who has been an investigator in some of the Pfizer-funded patient studies of the drug. "In the clinical trials, it appears to have a favorable tolerability profile, and may not have the same safety concerns about long-term use of estrogen."
However, Aprela's development has taken longer than expected. The FDA declined several years ago to approve bazedoxifene as a stand-alone drug because regulators wanted more information about the incidence of strokes and certain blood clots in clinical testing.
Bazedoxifene has been approved by European and Japanese regulators as a stand-alone treatment for osteoporosis. It is sold in Japan as Viviant and Conbriza in Europe.
There have also been challenges developing a satisfactory formulation of Aprela. Wyeth, which started working on Aprela in 1999, had originally planned to file for FDA approval of Aprela in 2007, but the submission has been repeatedly delayed since then.
"I think the FDA will be cautious about giving approval," said Ashwin Chatwani, section chief of general obstetrics and gynecology at Temple University School of Medicine in Philadelphia. He sees the need for a new option, however, because many women are reluctant to take PremPro or Premarin.
Some analysts have largely written off Aprela due to its development delays and Pfizer's focus on other new drugs, such as lung-cancer treatment Xalkori. Barclays Capital analyst Tony Butler said even if Aprela were approved by the FDA, health plans might not provide favorable reimbursement for such a drug. Expectations for the drug have diminished: some analysts don't include it in their Pfizer forecasts, while others predict annual sales of about $200 million by middecade.
In a study released last year, the incidence of endometrial hyperplasia—a thickening of the uterus lining that in some cases can lead to uterine cancer—was about 0.3% after one year of treatment with Aprela, comparable to the rate among those taking a placebo.
The study also found no differences in breast density after 12 months of treatment with Aprela, versus placebo. Breast density is a risk factor for breast cancer.
Adverse events among women taking Aprela in the clinical trial included back pain, headache, and inflammation of the nose and throat.
Menopausal women are desperately seeking answers as to the very best option they should consider in reducing hot flashes and the advent of osteoporosis. Will FDA approve this new menopause drug Aprela? We feel that unless Pfizer's clinical results can categorically prove minimal side effects we believe Pfizer may not push on with its approval, or indeed the FDA may delay or even decline its release onto the market.
Its a confusing time for many women as to which way to go and at the end of the day, products like Premarin (on the market since 1942) may be one answer due to its apparent low risk of typical side effects. We will keep an eye on this story and inform you of any further developments.
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