Tocagen Adopts “Seamless Pivotal Trial” for Brain Cancer Therapy

Xconomy San Diego — 

Three-year survival rates are rarely reported for a deadly form of brain cancer known as recurrent, high-grade glioma (HGG). Under the current standard of care, the median survival rate is seven to nine months.

Yet San Diego-based Tocagen (NASDAQ: TOCA) says five patients in a high-dose cohort of its gene therapy treatment Toca 511 and Toca FC are still alive after nearly 36 months. The results are from an early stage trial and involve a small subset of 23 patients, according to an update the company presented today in Philadelphia at the International Conference on Molecular Targets and Cancer Therapeutics. The Phase 1 trial has enrolled a total of 56 patients across seven sites.

Still, Tocagen says that after consulting with the FDA, it is accelerating and modifying its planned Phase 2 and Phase 3 trials into a single, combined pivotal trial known as Toca 5. In a speech last month, FDA commissioner Scott Gottlieb hailed the concept of a “seamless pivotal trial” as a way to save time and reduce drug development costs.

The two components of Tocagen’s gene therapy (Toca 511and Toca FC) are able to cross the blood-brain barrier and combine in the brain in a way that causes the cancer cells to produce anti-cancer compounds.

The first component is injectable vocimagene amiretrorepvec (Toca 511), which carries the genetic coding that enables cancer cells to produce a cytosine deaminase (CD), protein key to making cancer-fighting compounds. The second component is an antifungal compound 5-fluorocytosine (5-FC). The CD protein delivered to the cancer cells acts on 5-FC in a way that converts the antifungal drug into the cancer-fighting compound 5-fluoracil.

Tocagen says the advantage of its approach is treatment localized to the cancer cells.

Under Tocagen’s modified and accelerated plan for Toca 5, an additional 193 patients with recurrent high-grade glioma will be enrolled and pooled with 187 patients already enrolled.

Approximately 160,000 patients worldwide are expected to be diagnosed with HGG in 2017.