Arzoxifene Demonstrates Efficacy on Osteoporosis Prevention: Presented at NAMS

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Title: Arzoxifene Demonstrates Efficacy on Osteoporosis Prevention: Presented at NAMS
URL: http://www.pslgroup.com/dg/22DEA2.htm
Doctor's Guide
September 30, 2008

By Deborah Brauser

ORLANDO, Fla -- September 30, 2008 -- Arzoxifene, an oestrogen agonist/antagonist of the benzothiophene family, appears to have preventive effects on osteoporosis and has uterine safety in postmenopausal women with normal to low bone mass, according to research presented here at the North American Menopause (NAMS) 19th Annual Meeting.

"It's another new molecule in the whole family of SERMs [selective oestrogen receptor modules], oestrogen agonists/antagonists. Clearly, it's more potent than raloxifene. So from that point of view, call it the next generation," said lead author Wulf Utian, MD, Rapid Medical Research, Beachwood, Ohio, and founder of NAMS, in a presentation on September 26.

In their 2-year, phase 3, randomised study, Dr. Utian and colleagues evaluated the efficacy of arzoxifene on osteoporosis prevention through assessments of lumbar spine and hip bone mineral density (BMD). The drug's gynaecological safety was also evaluated through assessments of endometrial history, transvaginal ultrasound (TVU), incidence of vaginal bleeding, and adverse event reporting.

The study enrolled 331 postmenopausal women 45 to 60 years old. The women had an intact uterus and normal to low bone mass (femoral neck or lumbar spine BMD t-score between -2.5 and 0).

Treatment was arzoxifene 20 mg/day in 172 women and placebo in 159 women. All subjects were also given daily supplements containing 500 mg elemental calcium. After baseline evaluations, assessments of BMD were conducted by dual-energy x-ray absorptiometry every 6 months, endometrial sampling annually, and TVU at the study's end.

At the end of the trial, arzoxifene significantly increased lumbar spine (+3.2%, P < .001) and total hip BMD (+2.3%, P < .001) versus placebo. Arzoxifene also significantly decreased bone turnover markers C-telopeptide (-30%, P < .001) and type I N-propeptide (-31%, P < .001).

Neither endometrial hyperplasia nor cancer occurred in the arzoxifene group, although 2 subjects were affected in the placebo group.

The most progressive histological biopsy finding was weakly proliferative endometrium in 1 arzoxifene-treated subject. Vaginal bleeding occurred in 9 patients on arzoxifene and 11 patients on placebo. Uterine polyps occurred in 7 subjects in each group (hyperplastic polyps: arzoxifene 0, placebo 2; no malignant polyps in either group).

Change in endometrial thickness from baseline to endpoint was not significantly different between the groups (P = .06).

During adverse-event monitoring, vulvovaginal mycotic infection was the only event with a significantly higher incidence in the arzoxifene group versus placebo (7 vs 0, respectively; P = .02). There were no serious adverse events reported by the active-treatment group. In addition, arzoxifene was no different from placebo in the incidence of new or worsening hot flashes (arzoxifene 21, placebo 18; P = .87).

Dr. Utian stated, "[Arzoxifene] has no stimulatory effect on the endometrium, which was really important. And I was pleased that the bone density results were better than those we saw with raloxifene."

"If you look at the original data on raloxifene, it's interesting that there was actually an increase in vasomotor symptoms. And in this study there was no increase compared to placebo," he added.

"I think arzoxifene could really be a major player depending on the outcome studies that are being done," Dr. Utian concluded.

Funding for this trial was provided by Eli Lilly and Co.

[Presentation tile: Prevention of Osteoporosis and Evaluation of Gynecological Safety of Arzoxifene Versus Placebo Over 24 Months in Postmenopausal Women. Abstract S-7]

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