Early results from a Phase 2 clinical trial that tested the ability of the sex hormone estriol (TrimestaTM, Synthetic Biologics), in combination with Copaxone® (glatiramer acetate, Teva Neuroscience), in women with relapsing-remitting MS offer valuable insights which invite further study of this hormone as a potential approach for treating women with multiple sclerosis. Lead investigator Rhonda Voskuhl, MD (University of California, Los Angeles) and colleagues reported these findings today at the Annual Meeting of the American Academy of Neurology. This study was funded by the National MS Society, additional private donors, and the National Institute of Neurological Disorders and Stroke. Synthetic Biologics, a Maryland pharmaceutical company, provided the estriol for the trial at no charge.
Background: MS affects women two to three times as often as men. This demographic observation along with a series of other gender differences prompted the National MS Society to launch a special five-year, $10 million research initiative to explore the importance of the meaning behind these observations as they apply to the MS disease process. Among the findings from the 50 projects supported through this initiative was the possibility that the female hormone estriol may help protect against the immune attacks that underlie MS. Read more about this success.
Estriol levels naturally rise significantly during later pregnancy, a time when many women’s MS disease activity declines. This led some to suspect that estriol may be responsible for this easing of symptoms during pregnancy. Dr. Voskuhl and others explored this lead in mice with an MS-like disease. Later, with National MS Society support, Dr. Voskuhl conducted a small, early-phase trial of estriol in 12 women with relapsing-remitting MS. Results suggested that estriol might decrease disease activity.
The phase 2 study of estriol combined with Copaxone that was reported today was a direct result of this initiative. Phase 2 trials such as this one are designed to provide information about a therapy’s safety and potential effectiveness, but longer, larger Phase 3 studies are needed to confirm potential benefits and risks and to gain approval from drug regulators such as the U.S. Food and Drug Administration.
About Estriol: Estriol is one of several estrogen sex hormones in the body. Some forms of estrogen are available for prescription as methods of birth control and for the treatment of symptoms associated with menopause. Estriol has been used in Europe and Asia as a treatment for symptoms of menopause. The oral form of estriol used in this trial is not available in the United States.
The Study: Investigators recruited 164 women with relapsing-remitting MS between the ages of 18-50 at 16 sites across the U.S. All participants were on standard Copaxone therapy (injected daily under the skin) and were randomly assigned to also take estriol in pill form, or inactive placebo, for two years.
The primary outcome measured was the effects of the treatment combination on relapse rates. Secondary outcomes included several clinical and MRI (magnetic resonance imaging), measures of disability progression and cognitive function. There were also laboratory and gynecological tests built into the study to monitor for potential safety issues associated with the use of estriol and other estrogen hormones, including breast and endometrial (uterine) cancers.
Results: The preliminary results showed that the combination of Copaxone and estriol appeared safe over the two-year trial period, and there were no severe adverse events experienced by those in either treatment group.
After the first year of the study, those on the combined therapy had a significant reduction in relapse rates compared to those on Copaxone plus placebo, and secondary cognitive testing suggested possible benefit for those on the combined treatment. However, after the second year of the study, there was no statistical difference in relapse rates between those on Copaxone combined with estriol versus those on Copaxone combined with placebo.
Since these are preliminary results that were presented at a medical meeting, without peer review as of yet, we are likely to learn more about the significance and implications of the study’s results when the full findings are published in a peer-reviewed medical journal.
What’s Next?: “These preliminary results are intriguing and invite further research,” noted Timothy Coetzee, PhD, Chief Advocacy, Services, and Research Officer of the National MS Society. “We look forward to seeing the full data when it is published in a medical journal, which should help determine next best steps for the possible development of estriol as a potential therapy for women with MS.”