Very encouraging news! Thank you for sharing.
I recently read that this drug is fast tracked. Did I also read that one of them is already approved for other uses? What do you think that means for general availability? This seems like a pretty big deal to me but there seems to be very little buzz about it. Am I missing something?
Toca FC is just a special formulation of the drug 5-fluorocytosine, which is indeed approved for other uses.https://en.wikipedia.org/wiki/FlucytosineHowever, the Toca FC is no good without the Toca 511. The Toca 511 is a viral vector that delivers a gene (called CD) to tumor cells. This gene is a "suicide gene" that allows the conversion of 5-flucytosine to the chemotherapy drug 5-fluorouracil. Without the Toca 511 gene therapy, 5-flucytosine by itself would likely have little to no efficacy.
Stephen or others, I'm curious for thoughts on both why it possibly works so much better for IDH1mut and also why the phase 2 trial excludes oligo's, anyone with 1p-19q codel and mixed oligo-astro patients which are far more likely to be IDH1mut.That seems like an odd combination. Or is it simply that the excluded group has a better prognosis and slower disease progression and as such would not be as useful for the investigators to include in a fast track trial?
This is a good question. Although I've never seen any studies on IDH1mutant tumors and response to 5-fluorouracil (the active agent that 5-flucytosine/TocaFC is converted to), it could just be part of the general heightened chemosensitivity for IDHmutant tumors.The Tocagen trials were originally going to be only for GBM, until the Musella Foundation pushed to get grade 3 astrocytomas included. As you say, from a trial perspective it takes much longer to get results from lower grade and oligodendroglioma trials because of the better prognosis, but I have no idea what the reasoning was in this case (why anaplastic astrocytoma was included but not oligodendroglioma).
Thank you! What about fast track status? What does that actually mean? I hadn't read that, about Oligos.
Fast track status just means the process of getting the drug to approval will be expedited."The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need, with the goal of getting important new drugs to patients earlier. Fast Track designation allows for more frequent interactions with the FDA review team, including meetings to discuss the drug’s development plan to support potential drug approval and the opportunity to submit sections of an NDA on a rolling basis as data become available."http://tocagen.com/fda-grants-fast-track-designation-to-tocagens-toca-511-toca-fc-for-treatment-of-recurrent-high-grade-glioma/It was given this status 2 years ago. More recently it was given "breakthrough" status:"Breakthrough Therapy Designation from the FDA indicates preliminary clinical evidence demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapy. Breakthrough Therapy Designation intensifies FDA involvement to ensure an efficient drug development program and is an organizational commitment from the FDA to involve their senior managers."http://ir.tocagen.com/phoenix.zhtml?c=254300&p=irol-newsArticle&ID=2253987
FastTrack status cuts down on the FDA's processing time from maybe 1.5 years of review after submittal to maybe 6 months. The clinical trial time though is generally the biggest time chunk and Fast Track also allows changing the trial requirements to do combo phase2/3 or phase 2 only with a method of evaluating endpoints. So skipping a standalone phase 3 trial is really the major time saver.Tocagen is listing Sept 2019 as target completion of the trial, with Nov 2017 as the end of data collection. So its probably still a few years till non-trial patients can get it. Also since the delivery mechanism is a virus, seems likely that it might not work for lower grade patients due to intact BBB. Delivery into a resection cavity would partly circumvent that. So not only might it not work, it might also not get covered by insurance for lower grade patients.