FDA Lifts Full Clinical Hold On Proellex: Repros

Repros is expected to be allowed to run a single study under the new partial clinical hold status. The new low dose study is designed to explore both safety and signals of efficacy in an escalating dose fashion.

In the study, the company is expected to asses 5 different doses of Proellex (1, 3, 6, 9 and 12mg) with 1 mg being the first dose tested. Each dose will be compared to placebo with weekly assessments of liver function during both the placebo and drug period.

Repros said that the higher doses will not be studied until the company is confident that it is safe to proceed to the next dose and has reported the safety findings to the FDA.

In the trial, the subjects will be dosed with the active drug for 10 weeks, which will allow for adequate time to determine the impact of a given dose on trends in liver function.

Each dose will be tested in 12 different subjects and assessment of pharmacokinetic parameters will be obtained at start of dosing and end of the dosing period to determine overall and maximum drug exposure for a given dose.

Additionally, Repros will also monitor changes in menstrual bleeding patterns and ovulation as well as changes in endometrial thickness.

The FDA requires that an independent Drug Safety Monitoring Board be established and that the ‘Informed Consent’ clearly state the liver toxicity previously experienced with Proellex.

In a 120 patient study of Proellex as a treatment of uterine fibroids conducted in the US (roughly 40 subjects per arm) both a 12.5 and 25mg dose of Proellex were compared to placebo.

In this study both the 12.5 and 25mg doses achieved positive results when compared to placebo when menstrual bleeding was assessed.

The two doses also achieved improvement in quality of life measures using the Uterine Fibroid Symptom Quality of Life questionnaire developed and validated by Georgetown University and used in the development of device like treatments of uterine fibroids such as uterine artery embolization.

The study results demonstrated that there was no statistical difference in efficacy measures between the two doses. Importantly in the Phase II US trial a good percentage of women stopped menstruating. Over 80% of women on both the 12.5 and 25mg doses exhibited no menses during the three month trial whereas all women on placebo exhibited at least one menses.

Repros believes that the evaluation of ovulation and menstrual bleeding patterns in the low dose trial will provide strong evidence for efficacy warranting further development.

Further, Repros plans to proceed with the manufacture of the lower doses of Proellex capsules and hopes to begin dosing subjects this summer. Though the new study is more complex than that originally submitted to the FDA, the company believes it can complete the trial within roughly 18 months after first dose.

Presuming a safe and effective dose is identified and the FDA is in agreement, Repros anticipates that it will be able to proceed with large efficacy trials for both uterine fibroids and endometriosis, subject to available funds, or outlicense of the product to a major pharmaceutical company.