After a run of disappointments with its late-stage clinical development pipeline, Wyeth had some positive news to report as new data showed that Aprela, a novel combination of conjugated oestrogens and the as yet unapproved selective estrogen receptor modulator (SERM) bazedoxifene, reduced the number and severity of hot flashes in symptomatic post-menopausal women by up to 80% in a Phase III trial.
The US company’s shares gained 2.4% on the New York Stock Exchange as it released the positive trial data on Aprela from the annual meeting of the North American Menopause Society (NAMS). Wyeth also said it planned to file a US New Drug Application for the combination therapy in the second quarter of 2008, subject to final preparations such as further analysis and completion of product formulation, bioequivalence and clinical studies.
The company is relying on a clutch of new products to soften blows such as faltering demand for PremPro and Premarin (conjugated oestrogens), the hormone replacement therapies undone by their association with serious health risks such as breast cancer, stroke and coronary heart disease, and the coming US patent expiry on key antidepressant Effexor (venlafaxine). Wyeth believes Aprela, which is positioned as a new form of multifunctional menopausal therapy called tissue selective estrogen complex (TSEC), could bring in sales of US$2 billion a year.
The company presented data from two Phase III trials at the NAMS meeting. One was a 12-week study looking at 332 symptomatic postmenopausal women who, at baseline, were experiencing seven or more moderate to severe hot flashes per day or 50 or more hot flashes per week. Compared with placebo, Aprela was found to reduce significantly the number and severity of hot flashes, while incidences of breast pain and bleeding were less than 5% in both study arms, Wyeth reported.
In the other trial, Aprela was evaluated in 601 post-menopausal women with moderate to severe vulvar and vaginal atrophy. In this case, the combination improved symptoms of vulvar and vaginal atrophy versus placebo, as well as vaginal lubrication, sexual function and menopause-related quality of life. In addition, secondary data from both trials indicated that Aprela reduced sleep disturbances compared with placebo.
If approved, the combination of bazedoxifene and conjugated oestrogens “will be a new and different therapeutic option that has the potential to change the way physicians and their patients treat menopausal symptoms and prevent postmenopausal osteoporosis”, said Dr Ginger Constantine, vice-president, women’s health care and bone repair, for Wyeth Pharmaceuticals. As many as 50-90% of women going through the menopause experience vasomotor symptoms such as hot flashes, while 10-40% of post-menopausal women have symptoms of vulvar and vaginal atrophy.
Analysts see Aprela as a way of transitioning women onto Wyeth’s Viviant, a single-molecule version of bazedoxifene for the prevention of osteoporosis and menopausal symptoms, when problems such as hot flashes ease off in the post-menopausal phase. But the regulatory fate of the two drugs is also tied, and US approval of Viviant was delayed in April.
The Food and Drug Administration sent out an approval letter saying it needed to receive and analyse final safety and efficacy data from a Phase III study of bazedoxifene, as well as clear manufacturing and testing facilities for the drug. Wyeth is hoping Viviant will present a compelling alternative to Evista (raloxifene), Eli Lilly’s Eli Lilly osteoporosis drug in the SERM class.