It was always going to be a long shot, given how tough brain cancer is to treat and the litany of failures left in its wake, but Tocagen, perhaps inevitably, has seen its attempt flop, leading to a review of its operations.
Tocagen had recently moved its gene therapy asset known as Toca 511 and Toca FC into a phase 3, targeting patients with recurrent high-grade glioma (HGG) undergoing resection.
But the so-called Toca 5 test was a failure: It missed the primary endpoint of overall survival compared to standard of care treatment (11.1 months median compared to 12.2 months), with a p-value of more than 0.6.
To add to the woe, all secondary endpoints “showed no meaningful difference between the arms of the trial,” according to the brief update posted this morning.
This could also cause deeper issues within the company, and its chief Marty Duvall said that, in light of these data, “we will be conducting an operational review.”
Toca 511 is a cancer-selective immunotherapy comprised of an investigational biologic and an investigational small molecule, Toca FC, that are designed to be used together.
Toca 511 is an injectable retroviral replicating vector that encodes a prodrug activator enzyme, cytosine deaminase (CD). CD is derived from yeast, and humans do not naturally have this gene. Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD.
Toca FC, meanwhile, is an investigational oral prodrug, 5-fluorocytosine (5-FC), that is inactive as an anticancer drug. In animal models, Tocagen says it has seen 5-FC converted into the anticancer drug 5-FU at high concentrations in Toca 511-infected cancer cells that are producing CD.
Things looked brighter two years ago when the company got off an IPO in April 2017 worth $85 million toward its gene therapy tests.
Six months down the line, and the San Diego biotech said that after talks with the FDA, it would “immediately accelerate” development of its therapy by cutting out its midstage test and instead move into a pivotal late-stage trial: a Toca 5 trial.
It had been in a phase 2, but was amended and molded into a phase 3, although this did nothing to help its outcome. That year, Toca 511 was given the EMA’s PRIME designation and an FDA breakthrough tag for its phase 1 work.
The company is also running a phase 1b exploratory study of the therapy in advanced solid tumors (Toca 6), planning a trial in newly diagnosed HGG (Toca 7), and is also working on a candidate targeting PD-L1 before year end.
The biotech’s shares were eviscerated in early trading this morning, down 81% and into penny stock territory.