Across our three ascending-dose Phase 1 trials, Tocagen has treated 127 patients with recurrent high-grade glioma, or HGG, with Toca 511 & Toca FC. In these trials, potential benefits were observed, including durable objective responses, extended overall survival and a favorable safety profile. The recommended dose for future trials was also identified. Based on these Phase 1 clinical trial results, Tocagen is advancing a pivotal Phase 3 clinical trial for patients with first or second recurrent HGG undergoing resection.
The median overall survival of patients in the Phase 1 resection injection study, where Toca 511 was injected into the wall of the resection cavity after removal of the tumor, exceeds historical controls across a variety of previously reported clinical trials. Within the subset of 23 patients that were in the higher dose cohorts and would qualify for the Toca 5 trial, patients had a median survival of 14.4 months and 43.5% (10/23) of patients had clinical benefit (5 complete responses and 5 stable disease patients) . All five responders had a durable complete response, bringing the durable response rate (objective responses lasting at least 24 weeks) to 21.7%. Median duration of response had not been reached after a median follow up of 35.7 months (range: 14.1 to 44.9 months). Landmark overall survival rates at two and three years (OS24, OS36) were 34.8% and 26.1% respectively.
The U.S. Food and Drug Administration (FDA) granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG and the European Medicines Agency (EMA) has granted Toca 511 PRIME (PRIority MEdicines) designation for the treatment of HGG. These designations are granted to new products that treat serious diseases or conditions and demonstrate the potential to address an unmet medical need.
Tocagen has also obtained a $2 million Orphan-Drug Grant to support the Toca 5 trial and received Orphan-Drug Designation for the treatment of malignant glioma. Orphan-Drug Designation is a designation for a product that treats a rare disease or condition and which, if the product receives the first FDA approval for that disease or condition, may result in a period of regulatory exclusivity, subject to some exceptions.