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The purpose of the Phase 1 trial was to determine the safety, tolerabilityand immunogenicity of HspE7 plus escalating doses of adjuvant (50, 500, 1,000and 2,000 mcg of Poly-ICLC). All dose regimens were found to be safe and welltolerated. Immunogenicity analysis demonstrated that the adjuvant potentlyenhanced HPV16 E7-specific T-cell responses in subjects who demonstrated no orlow responses at baseline.
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"This Phase 1 trial has not only demonstrated HspE7's excellent safetyprofile, it has also provided compelling data to support the immunologicactivity of the compound and identified the appropriate dose regimen for ourfuture trials," said Gregory M. McKee, president and chief executive officerat Nventa. "We are very encouraged by these results and believe that HspE7may offer an important therapeutic benefit for the millions of women withCIN."
In the first cohort (500 mcg of HspE7 and 50 mcg of Poly-ICLC), which wasdesigned to establish a baseline for the study, there was limited HPV16E7-specific T-cell responses. In cohort 2 (500 mcg of HspE7 and 500 mcg ofPoly-ICLC), three out of four patients showed HPV16 E7-specific T-cellresponses. In the third cohort (500 mcg of HspE7 and 1,000 mcg of Poly-ICLC),HPV16 E7-specific T-cell responses were elicited in all four subjects and allof these T-cell responses represented significant changes from baseline,indicating that the responses were a direct result of treatment with HspE7.In the trial's fourth and final cohort (500 mcg of HspE7 and 2,000 mcg ofPoly-ICLC), two of five patients had significant increases in HPV16E7-specific T-cells from baseline while the remaining three patientsmaintained high levels of HPV16 E7-specific T-cells that were already presentat baseline. The absolute levels of HPV16 E7-specific T-cells in patients inthe fourth cohort were similar to levels observed in the third cohort. Thedata, therefore, support doses of 500 mcg of HspE7 and 1,000-2,000 mcg ofPoly-ICLC as appropriate for advancing into Phase 2 studies.
Findings from this trial verify the company's predicted mechanism ofaction for HspE7 as demonstrated by early preclinical models and support thecompound's potential to treat HPV16- induced CIN. HPV16 is the most commonsubtype of the HPV virus and is responsible for a significant percentage ofcases of CIN.
Phase 2 Development Plan Update:
Following discussions with, and input from, the U.S. Food and DrugAdministration (FDA), Nventa has finalized its protocol for a multi-center,randomized, double-blind, placebo-controlled Phase 2 trial of HspE7 inpatients with high-grade cervical dysplasia (CIN 2/3). Preparations have beenmade at approximately 40 clinical investigational sites in the U.S., Canadaand Latin America. The company has also designed a Phase 2 trial of HspE7 inpatients with low-grade cervical dysplasia (CIN 1). Evaluation of clinicalinvestigational sites in Europe and Latin America are underway. The companyintends to initiate one or both of these Phase 2 trials once it has securednecessary financing.
About Cervical Intraepithelial Neoplasia (CIN): <
