Tocagen is moving straight into a phase 3 trial of its gene therapy in cancer and thus needs more patients, but it has also been given a $2 million orphan drug grant for its efforts.
In an update, the San Diego biotech said it has changed its so-called Toca 5 study of its combo therapy Toca 511 and Toca FC, which is testing against patients with recurrent high-grade glioma (HGG), an aggressive type of brain tumor.
The biotech says that, after talks with the FDA, it will “immediately accelerate” development of its therapy by cutting out its midstage test and instead move into a pivotal late-stage trial, known as the Toca 5 trial. It had been in a phase 2, but this will now be amended and molded into a phase 3.
But this means more patients will be needed: 187 are already enrolled, but 193 more with HGG are needed to bring the total up to the 380 required. The primary endpoint will be the gold standard of overall survival (OS), which has proved difficult for previous treatments to hit in this form of brain cancer.
The company says that its primary endpoint assumes a median OS of 9.8 months for the control arm versus 14.3 months for the Toca 511 and Toca FC arm. Secondary endpoints include durable response rate, defined as complete or partial responses lasting at least 24 weeks, which is being assessed as a novel endpoint in the postsurgical setting of recurrent HGG.
Interim peeks at the data are slated for the second half of 2018 and first half of 2019. More patients will require more cash, but it’s had some help from the FDA, which has handed it a $2 million orphan drug grant, payable over four years, to support the Toca 5 trial.
This year, Toca 511 was given the EMA’s PRIME designation and FDA Breakthrough Tag for its phase 1 work.
“We are pleased with the outcome of our discussions with FDA under Breakthrough Therapy Designation, resulting in a pivotal phase 3 trial,” said Marty Duvall, CEO of Tocagen. “This advance allows us to expedite development of Toca 511 & Toca FC in support of our mission to bring clinicians and patients a new treatment option for this aggressive form of brain cancer.”
The company got off an IPO in April worth $85 million toward its gene therapy tests, although it has lost value, going from $12.45 a share in mid-April to $9.23 yesterday, where it also closed down by more than 3%, and with a market cap of just over $180 million. The biotech’s shares jumped 14% this morning, up $1.33 by 9:30 a.m. ET, but quickly went into the red by 4%.
A chunk of IPO haul had been earmarked for manufacturing scale-up and validation of Toca 511 and Toca FC.
Back before its IPO, the biotech released data showing that, among the 24 patients who received the higher Toca 511 doses in a phase 1 and met the inclusion criteria for the phase 2/3, Tocagen saw three complete responses and two partial responses.
At the time of the last data update, the responders were still alive 24 to 43 months after entering the study. The median overall survival for the 24 patients was 14.3 months; further updates are pencilled in over the coming days.
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 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.
Together, the biotech says that the Toca 511 and Toca FC combo “directly kills cancer cells and immune-suppressive myeloid cells resulting in activation of the immune system against the cancer.”