Date: 2012-05-09
Type of information:
phase: 2
Announcement: results
Company: Transgene (France)
Product: TG4001
Action mechanism: TG4001 is a therapeutic vaccine based on a non-propagative, highly attenuated vaccinia vector (MVA) which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). It has been designed to have a two-pronged antiviral approach: to alert the immune system specifically to HPV16-infected cells that have started to undergo precancerous transformation (cells presenting the HPV16 E6 and E7 antigens) and to further stimulate the infection-clearing activity of the immune system through interleukin-2.
Disease: CIN2/3 intra-epithelial neoplasia of the cervix due to infection with high-risk human papillomavirus
Therapeutic area: Cancer - Oncology
Country:
Trial details: This ongoing study enrolled 206 patients and aims at demonstrating the safety and activity of TG4001 in terms of histological resolution (complete disappearance of CIN lesions) and viral clearance (disappearance of the high-risk HPV genotypes present at baseline). The primary endpoint of the study is the histological resolution rate at 6 months in the sub-group of women with HPV16 mono-infection.
Latest
news: Transgene has announced that it has received from Roche, the former exclusive licensee of the product, 6-month headline results of the placebo-controlled study of TG4001 (RG3484) in women with CIN2/3 intra-epithelial neoplasia of the cervix due to infection with high-risk human papillomavirus (HPV). HPV16 mono-infected Viral 20/52 2/23 0.009 All genotypes Given the short dosing schedule (only three administrations of the therapeutic vaccine) and the fact that TG4001 was, unlike other clinical trials conducted by Transgene with its other MVA products, only injected in monotherapy, such data represent a strong proof-of-concept for the activity of the therapeutic vaccine, and are therefore encouraging for TG4001 and the MVA platform. The product has shown a similarly good safety profile as in the previous trials, with non-serious injection site reactions being the most frequent adverse events associated with the product. To move the product into phase 3 clinical trials and toward registration in CIN 2/3, it was expected, in addition to at least a doubling of the resolution rate compared to placebo (which was attained), a 60 % resolution rate in the HPV16 mono-infected population. This latter objective has not been reached and was set in light of the well-established high efficiency of conization, the existing surgical option for CIN2/3 patients. As a consequence, Transgene does not expect to further develop TG4001 in this indication and would rather address higher unmet medical needs, such as certain head and neck cancers and cervical cancer related to infection by HPV. For these latter indications, the market potential is far greater than for CIN2/3 and the product could efficiently be combined with chemotherapy. Further analysis of the care is necessary and will be conducted. Transgene expects to receive follow up data (notably on safety and viral clearance) on this trial within the next two years.
The main efficacy results at 6 months (6 months after treatment) are the following ones:
TG4001 Placebo P value
Histological 11/55 1/27 0.0498
resolution (20%) (4%)
clearance (38%) (9%)
TG4001 Placebo P value
Histological 32/129 6/63 0.0126
resolution (25%) (10%)
Viral 45/121 8/58 0.0013
clearance (37%) (14%)
Histological resolution and viral clearance in both groups are significantly higher in the experimental arm than in the placebo arm, with notably a fourfold difference between the arms in the HPV16 mono-infected patients group, all this with high significant statistic value.
