RE:RE:Thyroid cancerI remember a conversation with THTX management, some time ago so the details of my memory may not be accurate, but what I believe they said at that time was Thyroid cancer was included because it had very high sortilin expression in their lab tests. It was a very small market size but if they could prove out their concept with it, thay might just run with it and seeif they could get that indccation over the FDA approval finish line first.
qwerty22 wrote: 1) Why would you trust a random 3rd party website like this? Go to the source. The clinicaltrials website doesn't mention anaplastic thyroid cancer.
2) Read a bit deeper. Metastatic thyroid cancer has a Sortilin hit rate of 40%. Still not very higher but much better than the headline numbers. This cancer is in the basket arm. That means lower priority. It means sharing 20 recruitments with other cancers. Let's say they recruit 5 metastatic TC patients. There a good chance they hit 1 or 2 Sortilin expressors. At this stage that might be all they need to get a very early indication.
3) You have to understand IHC is not a quantitative method. It's fine within the boundaries of these experiments to set arbitrary numbers for the levels of Sortilin expression to compare between samples but it doesn't transfer over to other experiments all that well. Nobody has any idea what th1902 needs in terms of Sortilin expression to work. Taking one researcher's definition of over-expression and trying to paste it onto what th1902 needs is just bad science. JFM doesn't seem to understand this.
4) We don't know how thyroid made it into the trial. THTX may have done their own straining of samples and got better numbers. It might be the fda that pushed for this. It might be that metastatic thyroid cancer is completely untreatable and the unmet medical need is what makes this an attractive target. If we go on what JFM has found about Sortilin then yes thyroid cancer looks a bad choice. But why assume all these guys (remember the fda ok'd this) are 1diots making bad choices? Why not look for other reasons why thyroid cancer is included?
5) We can't keep going over this. There is a right time to introduce Sortilin testing. For several reasons it's not at the start of the program. If you think not testing for Sortilin is a killer blow to the program then you probably shouldn't be investing because they've clearly stated they aren't doing it yet. I don't think it matters all that much. If Sortilin was a well understood cancer target, with a massive history THTX could draw on to inform themselves then I could understand. If they were chasing HER2 then testing would be obligatory. Sortilin is not well understood, THTX has to do almost all the learning for itself. It might not seem to make sense but NOT screening for Sortilin in the first instance actually allows them to do that learning better. This is the first ever use of a Sortilin targeting drug in humans. EVER! We are in phase 1. That by it's very nature is exploratory and all about learning. JFM has it all worked out already through assumption.
JFM's big problem is he takes one scientific idea and looks at it in isolation. He can't actually locate it within the real-world, practical process of working your way through a clinical program. To me THTX are doing exactly that. We can't expect to have all the answers to all the questions now. Sortilin is just not well understood enough to allow that. THTX have to DISCOVER the answers. That's both the challenge and where the value lies.
jfm1330 wrote: It is so boring to follow Thera, no news, nothing, that I found a link saying that Thera was recruiting patients with thyroid cancer and also anaplastic thyroid cancer.
https://www.medifind.com/articles/clinical-trial/239307806
I was surpised by this distinction, so I made a little bit of research on anaplastic thyroid cancer (ATC) and sortilin expression. I ended up with a relatively recent article from 2172 stating that sortilin is not overexpressed at all in anaplastic thyroid cancer and that there was low to very low overexpression in two other types of thyroid cancers, follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). Baseline expression in non cancerous thyroid tissues is around 15, ATC 24, FTC 29.7, and PTC 40.8. Important to note that the article defines high sortilin overexpression at 100 or higher. So all these thyroid cancers types seems to be nowhere near high overexpression.
Again. I don't see how they can enroll patients in phase Ib without histological determination of real sortilin overexpression. Based on what the released publicly, this is the enormous weakness of this trial. How would you convince a patient with thyroid cancer to enroll in this trial if he would be aware of those numbers? Only out of total despair.
https://ajp.amjpathol.org/article/S0002-9440(17)30492-3/fulltext