Tocagen Adopts “Seamless Pivotal Trial” for Brain Cancer Therapy

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: [[ticker: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.

Author: Bruce V. Bigelow

In Memoriam: Our dear friend Bruce V. Bigelow passed away on June 29, 2018. He was the editor of Xconomy San Diego from 2008 to 2018. Read more about his life and work here. Bruce Bigelow joined Xconomy from the business desk of the San Diego Union-Tribune. He was a member of the team of reporters who were awarded the 2006 Pulitzer Prize in National Reporting for uncovering bribes paid to San Diego Republican Rep. Randy “Duke” Cunningham in exchange for special legislation earmarks. He also shared a 2006 award for enterprise reporting from the Society of Business Editors and Writers for “In Harm’s Way,” an article about the extraordinary casualty rate among employees working in Iraq for San Diego’s Titan Corp. He has written extensively about the 2002 corporate accounting scandal at software goliath Peregrine Systems. He also was a Gerald Loeb Award finalist and National Headline Award winner for “The Toymaker,” a 14-part chronicle of a San Diego start-up company. He takes special satisfaction, though, that the series was included in the library for nonfiction narrative journalism at the Nieman Foundation for Journalism at Harvard University. Bigelow graduated from U.C. Berkeley in 1977 with a degree in English Literature and from the Columbia University Graduate School of Journalism in 1979. Before joining the Union-Tribune in 1990, he worked for the Associated Press in Los Angeles and The Kansas City Times.