Pill with dienogest progestin under review
Research is eyeing an oral contraceptive (OC) formulation with a new progestin: dienogest. Results of an efficacy trial, presented at the 2008 Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG), indicate the formulation is effective, safe, and well tolerated.1
The new pill, under development by Bayer HealthCare Pharmaceuticals in Wayne, NJ, is a four-phasic OC composed of estradiol (E2) valerate and dienogest. Bayer's parent company, Bayer Schering Pharma AG in Berlin, filed for registration of the OC with European regulatory authorities in December 2007. Phase III studies are being conducted for U.S. regulatory authorities, reports Gerard Nahum, MD, senior director of medical affairs — women's healthcare, at Bayer HealthCare Pharmaceuticals.
No pills in the United States contain dienogest, one of several new progestins that have been synthesized in the last two decades. Bayer introduced an OC containing dienogest, trademarked as Valette, in Australia in 2007. Valette contains 2 mg dienogest and 30 mcg ethinyl estradiol.
Organon is conducting two pivotal Phase IIIa trials in the United States for a monophasic oral contraceptive containing E2 and another new progestin, nomegestrol acetate (NOMAC).
Dienogest and NOMAC have been designed to bind specifically to the progesterone receptor and not to other steroid receptors in an effort to avoid androgenic, estrogenic, or glucocorticoid side effects.
Check the results
To conduct the analysis of the E2/dienogest pill, scientists developed a multicenter, open-label study of women ages 18-50 years, using 20 28-day cycles. The four-phase formulation included two days of 3 mg E2 valerate, five days of 2 mg E2 valerate and 2 mg dienogest, 17 days of 2 mg E2 valerate and 3 mg dienogest, two days of 1 mg E2 valerate, and two days of placebo pills. A total of 1,377 women received the study medication.
In women ages 18-35 (998), 12 pregnancies occurred over an exposure of 16,608 cycles, yielding a Pearl Index of 0.94 [upper limit of two-sided 95% confidence interval (CI) 1.65]. Five of the pregnancies were attributed to method failure, yielding an adjusted Pearl Index of 0.40 (upper limit of the 95% CI 0.92). In the entire study population, 13 pregnancies occurred over an exposure time of 23,368 cycles for a Pearl Index of 0.73 (upper limit of 95% CI 1.24). Six of those pregnancies were attributed to method failure for an adjusted Pearl Index of 0.34 (upper limit of 95% CI 0.73).
The discontinuation rate due to adverse effects was 10.2%, report researchers. Nearly 80% of women were satisfied or very satisfied with treatment; emotional and physical well-being remained the same or improved in 89.7% and 86.4% of women, respectively.1
What is its impact?
Researchers also presented information on the pill's metabolic effects at ACOG's 2008 Clinical Meeting. To analyze the drug, researchers designed an open-label randomized study in which women ages 18-50 received a four-phasic regimen containing E2 valerate and dienogest or a sequential regimen of ethinyl E2 and levonorgestrel for seven cycles. The regimen was six days of 0.03 mg ethinyl E2/0.05 mg levonorgestrel, five days of 0.04 mg ethinyl E2/0.075 mg levonorgestrel, 10 days of 0.03 mg ethinyl E2/0.125 mg levonorgestrel, and seven days placebo pills. Scientists recorded individual-specific relative change in high-density lipoprotein and low-density lipoprotein cholesterol from baseline to Cycle 7. Hemostatic characteristics, carbohydrate metabolism characteristics, and hormone levels also were assessed.
Findings indicate the formulation with E2 valerate and dienogest showed a more favorable effect on lipid profiles and had a lesser effect on hemostatic characteristics than ethinyl E2 and levonorgestrel. No clinically relevant changes in metabolic characteristics were observed in either treatment group, researchers report.2
Bayer also is eyeing use of the E2 valerate/ dienogest formulation for the treatment of the prolonged, frequent, and excessive bleeding noted in dysfunctional uterine bleeding; however, the company says it is only seeking approval for the oral contraception indication at this time.3
References
- Nahum GG, Parke S, Wildt L, et al. Efficacy and tolerability of a new oral contraceptive containing estradiol and dienogest. Presented at the 56th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists. New Orleans; May 2008.
- Parke S, Nahum GG, Mellinger U, et al. Metabolic effects of a new four-phasic oral contraceptive containing estradiol valerate and dienogest. Presented at the 56th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists. New Orleans; May 2008.
- Bayer HealthCare. Bayer Schering Pharma paves the way to the next important oral contraceptive milestone. Press release. Berlin; Dec. 3, 2007.
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