Trimesta (oral estriol) is an investigational oral drug being developed for the treatment of relapses in multiple sclerosis (MS) and cognitive dysfunction in MS. Estriol has been approved and marketed for over 40 years throughout Europe and Asia for the treatment of post-menopausal symptoms. It has never been approved by the Food & Drug Administration for any indication. Estriol is a hormone that is produced by the placenta during pregnancy. Maternal levels of estriol increase in a linear fashion throughout the third trimester of pregnancy until birth, whereupon they abruptly fall to near zero.
It has been scientifically documented that pregnant women with certain autoimmune diseases experience a spontaneous reduction of disease symptoms during pregnancy, especially in the third trimester. The list of autoimmune diseases that have been seen to improve during pregnancy includes MS, rheumatoid arthritis, thyroiditis, uveitis, juvenile rheumatoid arthritis, ankylosing spondylitis with peripheral arthritis, and psoriatic arthritis. It has further been scientifically documented that these same pregnant women have high rates of disease relapse post-partum, particularly in the immediate three-month post-partum period.
The PRIMS study (Pregnancy In Multiple Sclerosis), a landmark clinical study published in the New England Journal of Medicine, followed 254 women with MS during 269 pregnancies and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy from pre-baseline levels and relapse rates then increased by 120 percent (p < 0.001) during the first three months post-partum before returning to pre-pregnancy rates.
Rhonda Voskuhl, MD, Professor, UCLA Department of Neurology, and Trimesta key opinion leader and principal investigator, has conducted scientific research on the role that estriol plays in creating immunologic privilege to the fetus in order to prevent its rejection by the mother. She believes that estriol’s immunomodulatory and anti-inflammatory properties may explain the remissions seen in certain Th1-mediated autoimmune diseases during pregnancy. Based upon these insights, this scientist has conducted clinical trials of Trimesta in female patients with relapsing-remitting MS.
Trimesta clinical trial funding
The ongoing Phase II clinical trial for relapsing-remitting MS in women is funded to completion with over $8 million in grant funding awarded to date.
The majority of the ongoing Phase II clinical trial for cognitive dysfunction in female MS patients is funded by private foundations.
Trimesta market opportunity
MS is a progressive neurological disease in which the body loses the ability to transmit messages along central nervous system nerve cells, leading to a loss of muscle control, paralysis, and, in some cases, death. According to the National Multiple Sclerosis Society, currently, more than 2.1 million people worldwide (approximately 400,000 patients in the U.S.), mainly young adults aged 20-50, are afflicted with MS and approximately 70% of MS patients are women.
Relapsing-remitting MS is the most common disease course at the time of diagnosis according to the National Multiple Sclerosis Society. Approximately, 85% of people with MS are initially diagnosed with the relapsing-remitting form, compared to 10-15% with progressive forms. Annual worldwide sales of current MS therapies are estimated at $14.1 million.
Cognitive dysfunction affects approximately 50% of MS patients according to the National Multiple Sclerosis Society.
There are currently nine Food and Drug Administration-approved therapies for the treatment of relapsing-remitting MS: Betaseron®, Rebif®, Avonex®, Copaxone®, Tysabri®, Gilenya®, Extavia®, Aubagio® and TecfideraTM. Many of these therapies provide only a modest benefit for patients with relapsing-remitting MS. All of these drugs except Gilenya®, Aubagio® and TecfideraTM require frequent (daily, weekly & monthly) injections (or infusions) on an ongoing basis and can be associated with unpleasant side effects (such as flu-like symptoms), high rates of non-compliance among users. Despite the availability of multiple FDA-approved therapies for the treatment of relapsing-remitting MS, the disease is highly underserved and exacts a heavy economic toll.