Wyeth's Pristiq (desvenlafaxine) -which the drug maker aims to promote as the first non-hormonal treatment for vasomotor symptoms associated with menopause - demonstrated a reduction in the number and severity of hot flashes in women in the first pivotal Phase III studies presented by the company.

Wyeth released the results of the trials evaluating the serotonin-norepinephrine reuptake inhibitor in VMS during the American College of Obstetricians and Gynecologists annual meeting in San Diego May 9. Two of the studies demonstrated a statistically significant reduction in hot flashes compared to placebo.

Pristiq is currently pending at FDA for the VMS indication. The NDA originally had an April 23 action date, but FDA extended the review until July to examine new data on a lower dose titration. The company's recently completed studies of 100 mg and 150 mg doses of Pristiq in VSM included a three-day 50 mg starting dose that led to reduced rates of nausea and adverse-event related discontinuations.

Wyeth is also evaluating desvenlafaxine for the treatment of major depressive disorder. That NDA was deemed "approvable" by FDA in January, and the company said it plans to submit a complete response letter in August, also including data on lower doses (¹ Also see "Wyeth’s Pristiq Deemed “Approvable” By FDA" - Pink Sheet, 23 January, 2007.).

The most recent data released by Wyeth on VMS include two studies showing a statistically significant benefit on symptoms between Pristiq and placebo and a third study that did not. One question will be if the data is convincing enough to encourage payors to reimburse for the drug.

According to a report and survey of U.S. payors released May 8 by Prudential analyst Tim Anderson, Wyeth will need to create significant demand at the physician and consumer level to overcome resistance to the treatment by payors for VMS.

Prudential commissioned the market research firm Cognet-X to survey payor attitudes on Pristiq, including 83 participants representing 76 unique health plans and 203 million lives.

"Generally, respondents did not appear to be terribly impressed with Pristiq as a treatment for VMS," Anderson said.

"Nearly two-thirds of respondents indicated they were not very impressed with the clinical profile of Pristiq, even in light of the potential problems with [hormone replacement therapy]," he reported. Most respondents suggested that the likelihood of tier 2 formulary placement for the product would be low. The survey was conducted prior to the April 23 action date on Pristiq.

The first of the studies to be released by Wyeth was a 12-month, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of Pristiq in the treatment of nighttime awakenings due to hot flushes and mood disturbances associated with menopause, with efficacy evaluations reported at week 12.

The trial enrolled 689 women with 50 moderate-to-severe HFs per week, randomly assigned to receive placebo or Pristiq 50 mg, 100 mg, 150 mg or 200 mg. The placebo group experienced a 50 percent reduction in the number of HFs, compared with 64 percent reduction for the 100 mg arm and 60 percent reduction in the 150 mg arm. The 200 mg arm had a significantly greater reduction in severity of HFs, Wyeth reported.

A second six-month randomized, double-blind placebo-controlled trial in 541 women with 50 moderate-to-severe HFs per week randomly assigned patients to placebo or either 100 mg or 150 mg arms of Pristiq. All groups significantly reduced the number and severity of HFs, number of nighttime awakenings and total mood disturbance score. Both DVS doses were statistically better than placebo for improvement in multiple HF endpoints, Wyeth reported.

A third 12-week study comparing efficacy and safety of DVS to placebo and tibolone (a hormonal treatment marketed outside the United States by Organon as Livial ) did not show a difference in average frequency and severity of HFs at weeks four and 12 from baseline between Pristiq and placebo. All treatment groups had a significant decrease in the two endpoints, while tibolone achieved a greater reduction in number and severity of HFs compared to placebo. The placebo effect was high at 58 percent reduction in HFs in the study, researchers concluded. The trial enrolled 451 postmenopausal women.

The most common side effect in all three studies was nausea, which generally resolved within three days.

If Pristiq were to be approved by FDA for VMS, a launch would not be delayed due to manufacturing issues at its Guayama, Puerto Rico, facility after the company announced the same day that those concerns have been resolved based on FDA's re-inspection of the site (² Also see "FDA Clears Guayama Manufacturing Facility" - Pink Sheet, 9 May, 2007.).

- Jessica Merrill (j.merrill@elsevier.com)

Wyeth’s Pristiq Shows Reduction In Hot Flashes In Menopausal Women

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