Despite the government shutdown, the FDA approved Duavee® for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis on October 3rd, 2013. Duavee, originally branded as Aprela®, is a combination tablet with conjugated equine estrogen0.45 mg and bazedoxifene 20 mg. Its unique combination—bone-building effects plus its ability to reduce hot flashes—makes it different.
Combination of Estrogen and SERM
You are probably familiar with the brand Premarin® that is the estrogen used in the combination tablet. The second component bazedoxifene is a new medicine. Bazedoxifene is a selective estrogen receptor modulator (SERM), which is the same class of medicine as Evista® (raloxifene, Lilly). SERMs are also referred to as estrogen agonist antagonists (EAAs) that refer to their “split personality.” In some tissues, SERMs work like estrogen and in others they have the opposite effect.
The pairing of a SERM and estrogen is categorized as a tissue selective estrogen complex (TSEC). Why would you add estrogen to a SERM? The motivation for adding an estrogen to a SERM stems from the concept that the benefits of each will be achieved with better overall tolerability. Estrogens help hot flashes and menopausal symptoms in contrast to SERMs that don’t help hot flashes and tend to even make them worse. Bazedoxifene prevents thickening of the lining of the uterus (endometrium) while estrogens stimulate growth of the endometrium. Therefore, the traditional use of progesterone to block the effects of estrogen on the uterus is not needed.
Clinical Trials with Duavee
Bazedoxifene was developed by Ligand Pharmaceuticals and Wyeth Research for use alone and also in a combination tablet with Premarin. The combination tablet studies focused on the question, “What happens if you add some estrogen to the SERM to relieve the hot flashes?” Duavee was tested in their series of studies named SMART (Selective Estrogen Menopause and Response to Therapy).
SMART 1 looked at the effectiveness of for postmenopausal osteoporosis prevention in a two-year trial. Duavee significantly increased bone mineral density at the lumbar spine and hip in comparison with those on a placebo. This combination also significantly reduced the daily number of hot flashes compared with placebo.
Further studies showed reduction in menopausal symptoms, no stimulation of the endometrium, and no problems with bleeding and spotting. The risk of blood clots in the legs was no more than estrogen or bazedoxifene alone.
Clinical Trials with Bazedoxifene Alone
Another large clinical trial evaluated bazedoxifene alone on the effectiveness of decreasing fractures in 7,500 postmenopausal women. Bazedoxifene was effective in lowering the risk of spine fractures (37% for the 20 mg dose) but not nonspine fractures, which is similar to Evista. In contrast to Evista, bazedoxifene did not decrease risk of breast cancer. Similar to Evista, bazedoxifene was generally safe and well tolerated, but offered no distinct advantage over Evista.
Duavee in the Marketplace
Pfizer who acquired Wyeth Research in 2009 will market Duavee starting in February 2014 in the US. Duavee will most likely be positioned as an alternative to combined hormone estrogen with progestin therapy. Duavee also provides another option for prevention of osteoporosis, particularly for women in the early postmenopausal years who are suffering moderate-to-severe menopausal symptoms. You may find more information online at Pfizer’s sponsored site: www.duavee.com.