Pfizer To Seek FDA Approval For Long-Stalled Menopause Drug

By Peter Loftus, Of DOW JONES NEWSWIRES

Pfizer Inc. (PFE) is preparing to
seek U.S. regulatory approval to sell a new menopause drug that
could pose an alternative to the company's older hormone-
replacement therapies, which have been tied to safety risks.

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 U.S.
Food and Drug Administration approval sometime this year,
Olivier Brandicourt, president and general manager of Pfizer's
primary care unit, said in an interview earlier this month.

Brandicourt said Aprela has the potential to reduce menopausal
symptoms including 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,"
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 (LLY) 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. (LGND).

"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 mid-decade.

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.

-Peter Loftus, Dow Jones Newswires; +1-215-982-5581; peter.loftus@dowjones.com

(END) Dow Jones Newswires
01-30-121321ET
Copyright (c) 2012 Dow Jones & Company, Inc.

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Pfizer To Seek FDA Approval For Long-Stalled Menopause Drug