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Genticel unveils initial results of phase 2 trial of GTL001 HPV immunotherapeutic candidate

Genticel has announced initial results from the ongoing randomized, double-blind, placebo controlled phase 2 clinical study of its immunotherapeutic candidate, GTL001, designed to clear HPV 16 and/or 18 infection.

While there was no statistical difference in viral clearance between treatment and placebo in the overall study population at 12 months, there was a clear separation in 2 predefined subgroups, namely patients with normal cytology and patients less than 30 years old at baseline.

Statistically significant viral clearance data at 18 months in the overall population will be determinant to trigger phase 3 preparation. These data will be reported in Q3 2016. The independent DSMB (Data Safety and Monitoring Board) recommended on January 26, 2016, the continuation of the study per protocol.

"The clinical goal of an HPV immunotherapy is to induce a long-lasting immune response in order to clear infection and prevent the progression to high-grade intraepithelial cervical lesions and cancer," said Margaret Stanley, Professor at the University of Cambridge, UK, renowned HPV immunology expert and advisor to Genticel.

"It has been noted with both other experimental and licensed onco-immune therapies, including the autologous cellular immunotherapy, Sipuleucel, that clinical activity is observed following a significant lag period. Therefore, I look forward to the availability of the 18-month clearance data."

The 24-month trial enrolled 239 patients (of which 232 were evaluable for the primary endpoint) and is evaluating the efficacy of GTL001, plus imiquimod, to clear HPV 16 and 18 infections, as compared to placebo in infected women 25 to 50 years old with normal (NILM), LSIL or ASCUS1 cytology and exclusion of CIN2+1 by colposcopy/histology. Previous studies indicate a natural viral clearance of 40 to 50% at 12 months in HPV 16/18 positive women.

An interim analysis at 12 months following the last injection shows no statistical difference in viral clearance rates between placebo and treatment. However, there is a statistically significant separation between the treated group compared to the placebo group in 2 prospectively defined subpopulations: women with normal cytology and women younger than 30.

These results strongly suggest that Genticel’s antigen delivery technology is effective in these 2 subgroups of patients.

While HPV positive women with normal cytology represent only 25% of the study population, they account for over 70% of the women infected with HPV 16/18 in the general population2. The results are also consistent with those of the phase 1 study of GTL001, in which the study population comprised exclusively women with normal cytology (NILM).

In addition, it has been observed that it takes longer to clear infection in women with abnormal cervical cytology than in women with normal cytology.

It has also been shown that higher viral loads at baseline are associated with longer time to complete clearance5. Because abnormal cytology, which represents over 70% of this phase 2 study population, is usually associated with higher viral load, it can be expected that viral clearance will take longer.

GTL001 viral clearance data collected at 18 months may therefore demonstrate a statistically significant therapeutic effect in the overall population at a later time point than 12 months. The phase 2 study continues to collect additional data that will be reported at 18 and 24 months.

Genticel CEO Benedikt Timmerman said: "The analysis to date shows clear separation in the viral clearance rates in two key subgroups and support our expectations to see superiority in viral clearance in the treated group at 18 months.

"We are excited to see how the trial develops and look forward to further analyzing these additional data."

"With € 21.7 million in cash & equivalents at year’s end, Genticel has enough financial resources to complete this 24-month duration study," concluded Mr. Timmerman.

In this phase 2 study, GTL001 appears to be generally safe and well-tolerated with the expected transient local reactions at injection site identified as the most common adverse events. No unexpected safety signal has been observed in the study.