The Woodlands, Texas, based Repros Therapeutics Inc., a development stage biopharmaceutical company focused on the development of oral small molecule drugs for major unmet medical needs in male and female health, has announced that it is optimistic that topline results from three clinical trials currently underway of its proprietary drug candidate Proellex can be reported by the end of the third quarter in 2016. Repros describes Proellex as a new chemical entity being developed for the treatment of symptoms associated with endometriosis and uterine fibroids. Proellex acts as a selective blocker of the progesterone receptor .
Repros notes that there are currently no FDA-approved orally administered drug treatments for long-term treatment of either endometriosis or uterine fibroids, and that the FDA has accepted an Investigational New Drug Application (NDA) for vaginally delivered Proellex.
Endometriosis is a common, complex, and sometimes debilitating condition of unknown cause in which cells of the tissue that normally forms the lining of the uterus — the endometrium — migrate to grow in a location outside the uterus, most commonly in the abdomen other pelvic organs: ovaries, vagina, cervix, bladder, bowels, rectum or the tissue lining the pelvis. This misplaced tissue responds to the woman’s menstrual cycle in the same way the tissue lining the uterus does: building up, breaking down, and shedding. Pelvic pain is the primary symptom of endometriosis, which is typically is experienced by women of reproductive age and sometimes associated with infertility.
Uterine fibroids are non-cancerous growths in the uterus that can range in size from microscopic to large masses. Most women with fibroids have no or mild symptoms, but those with larger growths can experience excessive, prolonged menstrual bleeding, bloating and pelvic pain. The usual treatment has been a hysterectomy, which completely removes the uterus. Repros cites a National Uterine Fibroids Foundation estimate that 80 percent of all women in the U.S. have uterine fibroids, and that one in four of these women will have symptoms severe enough to require treatment.
Current standards of care for both endometriosis and uterine fibroids consist of surgery or short-term treatment with gonadotropin-releasing hormone (GnRH) agonists — which are according to Endometriosis.org a group of drugs that have been used to treat women with endometriosis for more than 20 years — modified versions of a naturally occurring hormone known as gonadotropin releasing hormone, which helps to control the menstrual cycle. GnRH agonists induce a low estrogen, menopausal-like state, promote bone loss and are not recommended for use longer than six months.
Each of Repros Therapeutics’ three placebo controlled, double-blind Proellex studies has enrolled or will enroll approximately 45 subjects. Each study has a placebo arm and two drug arms administering 6 and 12 mg of Proellex respectively. Repros says the first reported component of the three studies will be after four months of continuous treatment followed by an off-drug interval to allow for return of menses.
For the purposes of this study, an effective dose of Proellex results in cessation of menses (amenorrhea) without any negative effects on bone mineral density, a criterion based on data obtained from several earlier studies in both endometriosis and uterine fibroids. Repros reports that to date, both low dose oral and vaginal Proellex have been generally well tolerated by trial participants.
Proellex To Move To Phase 3 Study For Endometriosis
Addressing endometriosis, Repros says previous studies administering Proellex at 25 and 50 mg dose in women with severe cases of the disorder showed substantial reductions in both associated pain and analgesic usage, noting that to date, the company has enrolled 41 subjects in a low dose trial of 6 and 12 mg Proellex in women with severe endometriosis (Biberoglu Berman Symptom Survey Score > 7 — for more detail on this evaluation scale see a discussion in this Open Source study: http://humrep.oxfordjournals.org/content/19/1/160.full) and who require analgesics to help control the associated pelvic abdominal pain.
Drawing on results from an interim analysis of the study data, Repros reports that women treated with placebo exhibited pain scores at the end of treatment that were 83% of baseline but showed no reduction in analgesic usage (100% of baseline), while women in the two groups receiving active Proellex treatment experienced clinically relevant reductions in both pain scores and analgesic usage. In the latter group, pain scores were 39% of baseline and analgesic usage was reduced to 23% of baseline.
Based on that assessment, the company says it has decided to end enrollment of the endometriosis study, convinced that the study data derived to date will be sufficient data to design a Phase 3 study based on the 40-45 subjects expected to be randomized, and projecting that topline results from this study should be available by the end of the 3rd quarter of 2016.
Proellex and Uterine Fibroids
Regarding uterine fibroids, Repros cites results from previous low dose oral and vaginally administered Proellex studies in which statistically significant outcomes for reduction in menstrual bleeding and general symptoms associated with uterine fibroids have been observed, as well as clinically meaningful reduction in fibroid volume. The company says two ongoing studies for uterine fibroids include a blood loss assessment via an alkaline hematin extraction from used sanitary products, noting that women effectively treated with Proellex do not menstruate and have no used sanitary products to analyze. Women receiving a placebo, on the other hand, will continue to menstruate. Consequently, the two Repros fibroid studies are designed to achieve statistical significance for key endpoints with a relatively small subject count.
Repros Therapeutics Inc. says it plans to request timely meetings with the FDA in order to determine what Phase 3 programs will be required for NDAs for these two indications.
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