In the preclinical studies, PTC299 was administered to mice harboring established human breast tumor xenografts. In these studies, PTC299 monotherapy significantly decreased human tumor and plasma VEGF levels, impeded tumor growth, and prolonged time to tumor progression in hormone- sensitive and -insensitive xenograft models. As assessed by dynamic contrast- enhanced magnetic resonance imaging (DCE-MRI), PTC299 also significantly reduced xenograft tumor volume and tumor perfusion, with effects beginning within one day of treatment initiation.
In the Phase I clinical studies, healthy volunteers received single doses or multiple doses through seven days of drug administration. PTC299 induced no serious, dose-limiting, or definitively drug-related adverse events.
Together, these preclinical and Phase Ia clinical data have supported the recent initiation of a randomized, dose-ranging Phase Ib/II clinical trial in patients with advanced breast cancer at New York University Medical Center. In addition to assessing longer-term safety and anti-tumor activity, the trial will evaluate tumor perfusion and metabolism and assess circulating VEGF and tumor markers.
Stuart Peltz, president and CEO of PTC Therapeutics, said: “The initiation of trials with PTC299 in patients with breast cancer provides further clinical validation of our proprietary GEMS technology.”