(+) Repros' IND for Proellex-V accepted by the FDA (Repros) - Jan 4, 2012 - Repros Therapeutics announced its IND for Proellex-V, or vaginally delivered Proellex for the purpose of significant fibroid size reduction and symptom elimination with the goal of avoiding surgery, has been accepted by FDA; Repros expects the P2 (N=36) ZPV-200 study to be completed in 2012 and anticipates to initiate P3 study
Anticipated P2 completion • Anticipated P3 trial initiation • IND submission
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Vaginal delivery significantly improves risk:benefit ratio while substantially reducing systemic drug levels
Company set to commence Phase 2 study early in 2012 and expects the trial will be completed in the same year
Institutional Review Board (IRB) grants approval to commence Phase 2 study
Clinical sites selected
Drug supplies manufactured
Animal studies suggest Proellex-V will give greater fibroid size reduction at much lower doses than oral doses tested previously
THE WOODLANDS, Texas - January 4, 2012 - Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced its Investigational New Drug Application (IND) for Proellex-V, or vaginally delivered Proellex, has been accepted by the FDA. The indication identified in the new IND is for the use of Proellex-V for the purpose of significant fibroid size reduction and symptom elimination with the goal of avoiding surgery. Approximately twenty percent of women of reproductive age in the U.S. have symptomatic fibroids with roughly 300,000 hysterectomies performed annually as a consequence. There is no approved chronic drug therapy for treatment of this debilitating condition.
Within the IND, the Company submitted animal model data that suggest vaginally administered doses of Proellex-V will exhibit profoundly greater anti-proliferative effects on tissues that respond to progesterone stimulation than oral Proellex administration. In addition, vaginal administration reduces systemic exposure to a small fraction of that seen with oral administration, and thereby avoids the first pass liver effects that were an issue with the highest dose, 50 mg, of the oral formulation. In animal studies, vaginal administration resulted in maximum exposure levels roughly 1/6th of that achieved with the same oral dose. At the same time, anti-proliferative effects were more than 4 times that of the equivalent oral dose. As part of the IND, the Company submitted data from a completed rabbit vaginal irritation study using the highest dose anticipated in human studies and in the final dosage format in which no irritation was observed.
Both this improved anti-proliferative activity and reduced circulating systemic drug levels should result in increased target organ selectivity with Proellex-V versus oral delivery. The FDA recognized this phenomenon and advised the Company in pre-IND discussions that the dose restrictions imposed on orally administered Proellex would not affect the Proellex-V program.
In efficacy studies using oral Proellex for the treatment of uterine fibroids, women experienced a nearly 50% reduction in mean fibroid size at a 25mg dose. When those women were then escalated to a 50mg oral dose for an additional four months, fibroid size was reduced to approximately 25% of the initial volume. Based on the assessment of fibroid symptoms as scored by Uterine Fibroid Symptom Quality of Life (USFQOL), women on oral Proellex were, in general, symptom free. The highest vaginal dose to be studied in the opening Phase 2 study, 12 mg, is expected to have greater activity than the oral 50 mg dose.
Repros has manufactured the clinical supplies for the upcoming study and has completed the initial one month stability study. The Company had submitted the Phase 2 protocol, also known as ZPV-200, as the initiating study as part of the IND. A central Institutional Review Board (IRB) has approved the protocol, which is necessary to commence the trial. Clinical sites have been engaged.
About ZPV-200
ZPV-200 is a 36 subject, single blind, placebo run-in, 3 month, 3 arm study comparing vaginally delivered Proellex-V doses of 3, 6 and 12 mg in women with confirmed uterine fibroids to baseline conditions. In addition to baseline and 3 month pharmacokinetics, efficacy endpoints will include change in Pictorial Blood Loss Assessment Chart (PBAC) scores, a preferred FDA endpoint, change in Uterine Fibroid Symptom Quality of Life Survey (UFSQOL) and change in fibroid size by MRI. Safety endpoints will include frequent assessment of complete liver panel tests and changes in endometrial conditions. Based on previous studies the Company believes results from both key safety parameters will not present any unexpected or adverse observations. The Company expects the study to be completed in 2012 with the next step being progression to Phase 3.
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Related News:
Repros' IND for Proellex®-V Accepted by the FDA
http://www.marketwatch.com/story/repros-ind-for-proellexr-v-accepted-by-the-fda-2012-01-04
Vaginal delivery significantly improves risk:benefit ratio while substantially reducing systemic drug levels
Company set to commence Phase 2 study early in 2012 and expects the trial will be completed in the same year
Institutional Review Board (IRB) grants approval to commence Phase 2 study
Clinical sites selected
Drug supplies manufactured
Animal studies suggest Proellex-V will give greater fibroid size reduction at much lower doses than oral doses tested previously
THE WOODLANDS, Texas - January 4, 2012 - Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced its Investigational New Drug Application (IND) for Proellex-V, or vaginally delivered Proellex, has been accepted by the FDA. The indication identified in the new IND is for the use of Proellex-V for the purpose of significant fibroid size reduction and symptom elimination with the goal of avoiding surgery. Approximately twenty percent of women of reproductive age in the U.S. have symptomatic fibroids with roughly 300,000 hysterectomies performed annually as a consequence. There is no approved chronic drug therapy for treatment of this debilitating condition.
Within the IND, the Company submitted animal model data that suggest vaginally administered doses of Proellex-V will exhibit profoundly greater anti-proliferative effects on tissues that respond to progesterone stimulation than oral Proellex administration. In addition, vaginal administration reduces systemic exposure to a small fraction of that seen with oral administration, and thereby avoids the first pass liver effects that were an issue with the highest dose, 50 mg, of the oral formulation. In animal studies, vaginal administration resulted in maximum exposure levels roughly 1/6th of that achieved with the same oral dose. At the same time, anti-proliferative effects were more than 4 times that of the equivalent oral dose. As part of the IND, the Company submitted data from a completed rabbit vaginal irritation study using the highest dose anticipated in human studies and in the final dosage format in which no irritation was observed.
Both this improved anti-proliferative activity and reduced circulating systemic drug levels should result in increased target organ selectivity with Proellex-V versus oral delivery. The FDA recognized this phenomenon and advised the Company in pre-IND discussions that the dose restrictions imposed on orally administered Proellex would not affect the Proellex-V program.
In efficacy studies using oral Proellex for the treatment of uterine fibroids, women experienced a nearly 50% reduction in mean fibroid size at a 25mg dose. When those women were then escalated to a 50mg oral dose for an additional four months, fibroid size was reduced to approximately 25% of the initial volume. Based on the assessment of fibroid symptoms as scored by Uterine Fibroid Symptom Quality of Life (USFQOL), women on oral Proellex were, in general, symptom free. The highest vaginal dose to be studied in the opening Phase 2 study, 12 mg, is expected to have greater activity than the oral 50 mg dose.
Repros has manufactured the clinical supplies for the upcoming study and has completed the initial one month stability study. The Company had submitted the Phase 2 protocol, also known as ZPV-200, as the initiating study as part of the IND. A central Institutional Review Board (IRB) has approved the protocol, which is necessary to commence the trial. Clinical sites have been engaged.
About ZPV-200
ZPV-200 is a 36 subject, single blind, placebo run-in, 3 month, 3 arm study comparing vaginally delivered Proellex-V doses of 3, 6 and 12 mg in women with confirmed uterine fibroids to baseline conditions. In addition to baseline and 3 month pharmacokinetics, efficacy endpoints will include change in Pictorial Blood Loss Assessment Chart (PBAC) scores, a preferred FDA endpoint, change in Uterine Fibroid Symptom Quality of Life Survey (UFSQOL) and change in fibroid size by MRI. Safety endpoints will include frequent assessment of complete liver panel tests and changes in endometrial conditions. Based on previous studies the Company believes results from both key safety parameters will not present any unexpected or adverse observations. The Company expects the study to be completed in 2012 with the next step being progression to Phase 3.
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