Repros Therapeutics Inc. said the FDA has accepted its investigational new drug application to conduct a Phase III study of Proellex as a treatment for anemia associated with uterine fibroids.

Current data suggest that the drug would have a "dramatic impact on bleeding" in these patients, obviating the need for blood transfusion, Matthew Kaplan, an analyst with Punk, Ziegel & Co, told BioWorld Today. Although iron supplements often are used to correct anemia (low blood count) in women with heavy bleeding from fibroids, these supplements don't impact the level of bleeding, Kaplan said.

Most women with fibroids do not have symptoms, but heavy bleeding and bulk-size fibroids are two of the biggest reasons why women end up in the clinic for the condition, said Kaplan.

Although surgical procedures - hysterectomy, myomectomy and uterine artery embolization - are available, Kaplan said there really is no drug to treat fibroid symptoms like bleeding and to shrink the fibroid as well. "There is no drug that can really treat that. So it's a wide open space," he added.

Repros President and Chief Executive Officer Joseph Podolski agreed, saying, "There is no drug a woman can take to replace [fibroid] surgery." But Proellex appears to work "handsomely" in that role, he told BioWorld Today.

Lupron (leuprolide), made by Lake Forest, Ill.-based TAP Pharmaceutical Products Inc., is approved for uterine fibroids, but it can't be used for long periods of time due to the potential risk of bone loss, Kaplan and Podolski noted.

One dosing regimen that is being explored for chronic use of Proellex is to temporarily take patients off the drug until they have a menstrual cycle, which could occur within 30 days, then put them back on treatment, Kaplan said.

Women who participated in the anemia trials have become symptom-free, Podolski said. Al Poindexter, a study investigator at Baylor College of Medicine in Houston, has asked the company to seek compassionate use of the drug to allow patients to continue on the drug under a year extension, Podolski said.

Proellex, which is Repros' lead drug, is a selective blocker of the progesterone receptor and is targeted for the treatment of uterine fibroids, endometriosis as well as fibroid induced anemia. The company expects to initiate registration Phase III trials in the first quarter of 2008 with Proellex for the short-term treatment of uterine fibroid induced anemia and for the chronic treatment of uterine fibroids.

The larger market for Proellex would be for uterine fibroids, which affects an estimated 12 million Americans, and endometriosis, which affects 6 million, Kaplan said. He added that the market for fibroid-induced anemia would be smaller, but he still sees the drug filling a void in this indication.

According to The Woodlands, Texas-based Repros, the new clinical trials will open with two identical registration quality Phase III studies, enrolling 65 patients each. The goal of the study is to improve hemoglobin levels. The IND is based on positive findings in a Phase IIb trial of the drug, in which the hemoglobin improvement was found to be statistically and clinically significant.

One of the soon-to-start Phase III studies will be conducted in 15-20 sites in the U.S. and the second study in several sites abroad. The trials will consist of three parallel arms each consisting of placebo, 25mg and 50mg of Proellex, the company said. Each study will enroll 65 patients unevenly distributed between placebo (15 patients) and 25 and 50 mg Proellex (25 patients each). Patients will be treated with Proellex or placebo for three months. The work has been awarded to a contract research organization.

In addition, Repros management has awarded contracts for the pivotal registration studies of Proellex for the indication of chronic treatment of symptomatic uterine fibroids, as well as the large open label safety studies necessary to support chronic use of the drug. These protocols will be submitted to the FDA for comment before initiation, the company said. Repros' other drug, Androxal, a single isomer of clomiphene citrate, is designed to restore normal pituitary response in men resulting in normalization of testosterone and luteinizing hormone levels. Androxal is entering two Phase IIb clinical trials in the second quarter of 2008. It is estimated that 13 million men in the U.S. are testosterone deficient, the company said.