15. Toca 511/Toca FC

purple brain
Tocagen is continuing a phase 2/3 trial of the Toca 511/Toca FC gene therapy in newly diagnosed glioblastoma. (Raman Oza/Pixabay)

Toca 511/Toca FC
recurrent high-grade glioma
Sponsor: Tocagen

The third failed cancer drug for high-grade glioma (HGG) on our list provides further evidence should it be needed that the disease seems able to shrug off just about anything pitted against it.

After AbbVie’s Depatux-M and Bristol-Myers Squibb’s Opdivo failed to make the grade, Tocagen was left as one of the last companies with a late-stage program in the cancer, but in September, it revealed that its Toca 511/Toca FC gene therapy was also a bust. It missed the primary endpoint of overall survival compared to standard-of-care treatment in the Toca 5 trial and flunked all its secondary outcome measures as well.

With the combination drug making up effectively all of Tocagen’s pipeline, the outcome forced the biotech to take drastic measures. It axed two-thirds of its workforce, around 55 employees, and started a review of its future options.

Toca 511 is an injectable retroviral replicating vector that is delivered to cancer cells and encodes a prodrug activator enzyme called cytosine deaminase (CD). Toca FC, meanwhile, is an investigational chemotherapy prodrug, 5-fluorocytosine (5-FC), that is inactive until catalyzed by CD. The rationale for the therapy is that only cancer cells express CD and so activate the chemo component of the treatment, sparing healthy tissues.

Tocagen is continuing a phase 2/3 trial of the therapy in newly diagnosed glioblastoma and a phase 1 trial in non-muscle invasive bladder cancer, but also had some more encouraging news to report from Toca 5 at the Society for Neuro-Oncology Annual Meeting in San Diego last month that could throw the program a lifeline.

With all the usual caveats about digging for gold in subgroup analyses from failed trials, Tocagen says that in a group of 60 patients who had a second recurrence of HGG there was a 57% risk reduction for death compared to standard of care, a doubling of survival, with the greatest benefit in patients with an IDH1 mutation.

If Toca 511/Toca FC does turn out to be terminal, it would leave Celgene’s proteasome inhibitor marizomib as one of the few drugs with the potential to generate positive late-stage results in glioblastoma within the next couple of years.

15. Toca 511/Toca FC