Antisense Pharma’s Trabedersen in Malignant Brain Tumors: Phase IIb Data Published in Neuro-Oncology
Antisense Pharma announced that their international, randomized and active-controlled Phase IIb study G004-AP 12009 is published in the official journal of the American Society for Neuro-oncology (SNO). The investigated drug trabedersen (AP 12009) is a gene silencing antisense compound – a phosphorothioate oligodeoxynucleotide – designed to selectively downregulate the production of transforming growth factor-beta 2 (TGF-beta2) at the translational level. The trial revealed encouraging efficacy results. Based on these data, a pivotal Phase III study in recurrent or refractory AA patients (SAPPHIRE) has already started.
The completed randomized, active controlled Phase IIb clinical study evaluated efficacy and safety of two doses of trabedersen (10 µM; 80 µM) in comparison to currently approved standard chemotherapy (TMZ or PCV) in high-grade glioma patients. Very good safety and tolerability of trabedersen had been demonstrated in three prior clinical Phase I/II studies with 24 patients with recurrent high-grade glioma. In the subsequent Phase IIb study 134 out of 145 randomized patients with either recurrent or refractory anaplastic astrocytoma (AA, N=39) or glioblastoma multiforme (GBM, N=95) received treatment. Trabedersen was locally administered using an intratumoral catheter and a portable pump allowing outpatient treatment. GBM patients had a comparable overall survival rate among the three treatment groups (10 µM trabedersen, 80 µM trabedersen, standard chemotherapy). In the pre-specified GBM subgroup with the two prognostic factors age = 55 years and Karnofsky Performance Status > 80% (about 40% of the GBM patients in this study), treatment with 10 µM trabedersen resulted in long-term survival rates at two and three years that were three times higher than those of patients who had received standard chemotherapy. In AA patients, the efficacy of 10 µM trabedersen was even more pronounced. A significantly higher tumor control rate of trabedersen treated patients was observed at 14 months when compared to patients who had received standard chemotherapy (58% vs. 0%; p=0.0032). Similarly the overall response rate at 14 months was significantly higher (p=0.0337). The duration of this response exceeded the 6-month treatment period impressively with 29.1 vs. 8.0 months (p=0.10) and the two-year survival rate were clearly improved under trabedersen (83.3% vs. 41.7%). Importantly, these trabedersen effects were associated with a median overall survival benefit of 17.4 months vs. standard chemotherapy (39.1 months vs. 21.7 months, non-significant).
Original publication: Bogdahn U. et al, "Targeted Therapy for High-Grade Glioma with the TGF-β2 Inhibitor Trabedersen: Results of a Randomized and Controlled Phase IIb Study." Neuro-Oncology 2010.
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