Investigational SERM Increased Lumbar Spine BMD by 2%


SAN ANTONIO — The next generation selective-estrogen receptor modulator lasofoxifene increased vertebral bone mineral density better than did raloxifene, according to the findings of a company-sponsored trial presented at the annual meeting of the American College of Rheumatology.

In the study, 410 postmenopausal women were randomly assigned to one of two doses of lasofoxifene, 0.25 mg or 1 mg daily; raloxifene at 60 mg daily, or a placebo.

The half-life of lasofoxifene is about a week versus 28 hours for raloxifene, according to Andy Lee, a director with Pfizer Global Research and Development, New London, Conn.

A new drug application for lasofoxifene has been submitted to the Food and Drug Administration for approval.

Lasofoxifene increased bone mineral density (BMD) at the lumbar spine by a mean of about 2% after 2 years of treatment. That compared with no mean improvement in spine BMD—but no density loss—in the patients assigned to raloxifene, and a 2% decrease in density in patients assigned to placebo.

BMD at the total hip improved by a mean of 1% for patients taking either raloxifene or lasofoxifene; total hip BMD remained the same in patients taking placebo.

Although responsiveness to lasofoxifene varied, overall more women responded to lasofoxifene than to raloxifene, Mr. Lee said.

Spine density improved or was at least maintained in 90% and 93% of the patients in the low- and high-dose lasofoxifene groups, respectively. That compared with 77% of the patients who took raloxifene and 65% of the patients who took placebo.

Changes in bone turnover markers were also greater with lasofoxifene. N-telopeptide levels, for example, decreased by a mean 35% in the patients on lasofoxifene, versus 15% in the patients on raloxifene.

And the new drug reduced LDL cholesterol levels by a mean of 20% versus 12% for raloxifene.

Future trials of lasofoxifene will use the 0.25 mg dose, Mr. Lee said.

Some women treated with lasofoxifene experienced hot flashes, leg cramps, and increased vaginal moisture, but overall the two drugs were tolerated similarly.

None of the lasofoxifene trials has shown an increase in endometrial hyperplasia or vaginal bleeding, Mr. Lee said.

Likewise, there have been no reports of urogenital prolapse, a problem that has plagued earlier selective estrogen receptor modulators.