July 18, 2012 -- As a reminder, Advaxis initiated the multicenter, randomized, single blind, placebo-controlled, Phase II clinical trial of ADXS-HPV for the treatment of cervical intraepithelial neoplasia (:CIN) in April 2010. The study is designed to assess the safety and ef? cacy of ADXS-HPV for the treatment of CIN grade 2/3, which is late stage cervical dysplasia that requires surgery to prevent invasive cancer. Numoda Corporation is Advaxis’ strategic partner in the conduction and execution of this trial.
The study has three cohorts consisting of 40 patients each: 30 patients receive 3 doses of ADXS-HPV at 50 million, 330 million or 1 billion cfu and 10 patients receive 3 doses of placebo. The primary objective of this study is to determine a safe dose of ADXS-HPV for the treatment of CIN 2/3. Ef? cacy is determined by an adjudicated panel of pathologists who are blinded to treatment and conduct microscopic assessments of the tissue removed at pretreatment biopsies and during their treatment surgery to determine if the lesions have regressed or returned to normal. Immunogenicity and HPV DNA data will be collected, as well.
Dosing of patients began in late May 2010, and total of 120 patients will be enrolled in this trial. Following is the summary of the Cohort 1 results:
• In the ADXS-HPV arm, 52% of CIN 2/3 lesions regressed from CIN 2/3 to CIN 1 or normal. This means surgery is longer be required. The dose in cohort 1 is about 1/20th of the dose being used in trials of ADXS-HPV in cervical cancer.
• This 52% regression rate of ADXS-HPV with the lowest dose tested is very encouraging. According to the American Academy of Clinical Research’s Task Force on the Treatment and Prevention of Intraepithelial Neoplasia, 50% objective regression rate with a new treatment agent is considered clinically meaningful.
• Further, according to O’Shaughnessy, et al 2002, CCR, 8:314, “An improvement in CIN 2/3 to either pathologically normal cervix or of CIN 3 to CIN 1, with no new CIN 2/3 lesions appearing in at least 50% of the treated patients, is evidence of clinical bene? t of the new agent.”
• In the cohort 1 trial, 40% of CIN 2/3 lesions spontaneously regressed in the placebo arm. This is within the range reported in the scienti? c literature of 35%-43% (Wright, et. al. 2003. Am J Obstet Gynecol, Am. J. Obstet. Gynecol. 289:295).
• ADXS-HPV is safe. Less than 1/3 (29%) of the patients treated reported any side effects associated with treatment. Those that occurred were mild and self-resolved or responded quickly to treatment.
• No SAEs (serious adverse events) were reported.
This study is enrolling at several sites in the U.S. with a target enrollment of 120 patients across the 3 dose cohorts. Enrollment in cohort 2 (the mid dose) is 75% complete and is expected to report in early Q4 2012.
We are encouraged by the positive preliminary results of this Phase II trial especially at this low dose. ADXS-HPV at low dose meets 50% ef? cacy target. With cohort 2 dosage 6 times higher and cohort 3 dosage 20 times higher, higher response rates with continued safe administration are expected to achieve.
CIN 2/3 is the precursor to cervical cancer. CIN is diagnosed in 450,000 American women annually. Progressive CIN is currently treated with surgery to prevent cancer from occurring. However, this treatment is associated with a number of problems, which include the development of an “incompetent cervix” i.e., a condition that prevents women from carrying a baby to full term. The typical CIN patient is a woman between 25 and 45 years of age. Although surgery is a viable short-term solution for the condition, it does not address the cause of the disease, which is a human papilloma virus (:HPV) infection. Women who require surgery once may need it again. Current HPV vaccination products have not demonstrated effectiveness against active HPV infections.
The goal of this treatment is to prevent progression to cervical cancer and to eliminate the need for surgery and subsequent obstetric risks. With these positive preliminary results, ADXS-HPV seems on track to achieve this goal.