A very basic note on other telomerase inhibitors
Posted: Fri Apr 19, 2019 3:51 pm
Imet is not the only telomerase inhibitor. As everyone with any familiarity with this field should know, AZT was the first telomerase inhibitor, followed by its other anti-retrotranscriptase cousins (e.g. ddI).
Those who keep saying that "imetelstat is the only telomerase inhibitor tested in humans" need to read a few 1990s papers
https://www.researchgate.net/profile/St ... 000000.pdf
Now, I'm all about combinations... but the FDA, not so much. The fewer drugs in a combo, the better for approval and testing. There might be a theoretical advantage to using imet AND AZT together... but we don't know. And JNJ does know.
Notice that JNJ dropped GERN and immediately picked up ARGX. It's possible that JNJ thinks that they only need one telomerase inhibitor in an anti-cancer cocktail... or at least, they're likely to only be allowed to use one. This in spite of the public data on combinations (see paper linked below).
If GERN's patent on "any telomerase inhibitor" in AML, MDS, or MF holds up, then GERN could prevent the use of AZT in those patients. Personally I don't see that patent as valid (it's well established that you can patent specific chemicals, but not vague concepts), but it's a possible threat to the ARGX patients... hopefully JNJ's lawyers will be able to claim that the AZT MOA is "apoptosis induction" instead of "telomerase inhibition", and keep GERN from shutting down the trial.
Public information indicates that it's generally more effective (and safer) to use smaller doses of more drugs in combination. That said, I don't have the data from Janssen's brute-force screening labs... they can generate data that is far more extensive and statistically significant than any starving postdoc can do with a few thousand dollars in an academic lab.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281941/
Those who keep saying that "imetelstat is the only telomerase inhibitor tested in humans" need to read a few 1990s papers
https://www.researchgate.net/profile/St ... 000000.pdf
Now, I'm all about combinations... but the FDA, not so much. The fewer drugs in a combo, the better for approval and testing. There might be a theoretical advantage to using imet AND AZT together... but we don't know. And JNJ does know.
Notice that JNJ dropped GERN and immediately picked up ARGX. It's possible that JNJ thinks that they only need one telomerase inhibitor in an anti-cancer cocktail... or at least, they're likely to only be allowed to use one. This in spite of the public data on combinations (see paper linked below).
If GERN's patent on "any telomerase inhibitor" in AML, MDS, or MF holds up, then GERN could prevent the use of AZT in those patients. Personally I don't see that patent as valid (it's well established that you can patent specific chemicals, but not vague concepts), but it's a possible threat to the ARGX patients... hopefully JNJ's lawyers will be able to claim that the AZT MOA is "apoptosis induction" instead of "telomerase inhibition", and keep GERN from shutting down the trial.
Public information indicates that it's generally more effective (and safer) to use smaller doses of more drugs in combination. That said, I don't have the data from Janssen's brute-force screening labs... they can generate data that is far more extensive and statistically significant than any starving postdoc can do with a few thousand dollars in an academic lab.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281941/