Results from a Phase III program evaluating imiquimod 3.75% and 2.5% creams for the treatment of EGW, applied once daily for up to 8 weeks, demonstrated that both were well-tolerated and more efficacious than placebo, according to data presented at the annual Human Papillomavirus (HPV) Conference in Montreal, July 3 - 8. Investigators found that efficacy was greatest for imiquimod 3.75% with an enhanced safety profile. The data were included in a New Drug Application (NDA) accepted for review by the U.S. Food and Drug Administration for an eight-week treatment regimen of imiquimod 3.75% for the treatment of EGW.
“From a clinical perspective, I'm encouraged that we saw strong efficacy results with the 3.75% formulation along with an enhanced safety profile”
Two Phase III double-blind, placebo-controlled efficacy and safety studies of imiquimod cream evaluated both per-protocol (PP) populations (only participants who completed the study) and intent-to-treat (ITT) populations (all participants who began the study regardless of whether they completed it). Complete clearance of all warts - defined as clearance of baseline and emergent warts across several anatomical locations - in the PP population was achieved in 33.8 percent of patients on imiquimod 3.75% cream, compared to 11.5 percent on placebo cream. Complete clearance of all warts in the ITT population was achieved in 28.3 percent of patients on imiquimod 3.75% cream, compared to 9.4 percent on placebo cream. Additionally, efficacy was greater in females in both the PP and ITT populations than males for all primary and secondary efficacy measurements, and in the PP population 43.1 percent of females on the 3.75% formulation achieved complete clearance compared to 22.7 percent of males.
In subjects with complete clearance, 12-week sustained complete clearance was assessed. Of those who achieved initial complete clearance and entered the 12-week follow-up, complete clearance was sustained in 69.6 percent of subjects on imiquimod 3.75% cream.
"From a clinical perspective, I'm encouraged that we saw strong efficacy results with the 3.75% formulation along with an enhanced safety profile," said Daron Ferris, M.D., Departments of Family Medicine and Obstetrics and Gynecology, Medical College of Georgia at Augusta. "Most notably, there was a low incidence of treatment-related adverse event reports of itching (2.5%), burning (5.8%) or pain (6.8%) at the application site, and no treatment-related reported systemic adverse events of headache or flu-like symptoms."
In the Phase III program, 1.5 percent, 1.6 percent and 0.5 percent of subjects discontinued early due to safety-related reasons for imiquimod 3.75%, 2.5% and placebo, respectively. Rest periods from treatment for adverse reactions were required in 31.5 percent, 27.4 percent and 2.0 percent of subjects on imiquimod 3.75%, 2.5% and placebo, respectively. Severe local skin reactions were experienced by 16.3 percent, 15.0 percent and 1.0 percent of subjects on imiquimod 3.75%, 2.5% and placebo, respectively.
The approved 5% imiquimod formulation, called Aldara®, is indicated for the treatment of EGW, for use three times a week, for up to 16 weeks, a lengthy dosing schedule. The intent of the clinical studies for imiquimod 3.75% and 2.5% was to fill the need for a shorter treatment regimen which may increase patient adherence to treatment. Additionally, the key efficacy endpoint in the imiquimod 3.75% trial was clearance of all warts (those visible at baseline and those that appeared during treatment) in all anatomic locations while the efficacy endpoint of the original Aldara, imiquimod 5%, Phase III program was to clear only baseline/target warts in a defined area.
"One of the goals with imiquimod 3.75% was to develop an EGW product with a more manageable treatment regimen," said James Lee, M.D., Ph.D., Chief Medical Officer, Graceway Pharmaceuticals, LLC. "Patient compliance can be a challenge with treatments that last up to 4 months. With a more intuitive daily dosing schedule over a shorter duration, complemented by an enhanced safety profile, we hope that patients will be more motivated to complete treatment and experience the full benefit of therapy."
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