‘Trojan horse’ drug treated British patients with six different forms of cancer | Hacker News Reader

‘Trojan horse’ drug treated British patients with six different forms of cancer

thelondoneconomic.com

87 pointssdan33 comments

I'm hoping here that HN isn't going to be too taken in by a good PR strategy from the biotechs who are supporting the clinical trials here (Seattle Genetics and Genmab - see here: https://www.clinicaltrials.gov/ct2/show/NCT03485209)

I mean, it's interesting data, and any step forwards in treating cancers (especially solid tumours) is great... but this isn't especially novel. Toxin-bearing antibodies like this have been worked on now for years; indeed, there are examples which have successfully made it all the way through large phase III trials and onto the market, which takes many years.

e.g. https://www.medicines.org.uk/emc/product/2859 and https://www.medicines.org.uk/emc/product/9537/smpc

Not novel isn't the same thing as not news. As a tech site, we read lots of articles about new JavaScript libraries reimplementing techniques discovered in the 60s.

Can we not have one breathless article about an incremental improvement in cancer drugs without everyone in the know scoffing about how it is not revolutionary?

> Can we not have one breathless article about an incremental improvement in cancer drugs without everyone in the know scoffing about how it is not revolutionary?

this will probably happen about the same time that the headlines stop presenting incremental things as revolutionary..

The price has not yet been set. This will be worked out based on the success of the drug, the number of cancers it treats and what individual markets can bear.

Why is it not based on the cost of the treatment?

I think they're trying to estimate how long it's going to take to break even on the cost of research.

Because we are supposed to pay for results?

Well, that depends on your personal economic philosophy.

Yeah this is tax/charity funded research. It’s not a risky private investment as far as I can tell.

The trials are being run by Seattle Genetics and Genmab.

https://www.clinicaltrials.gov/ct2/show/NCT03485209

Because it's not yet been approved for sale, and in fact isn't even close - it's still at a very early stage of development.

From https://en.m.wikipedia.org/wiki/Prescription_costs

“A study has placed the amount spent on drug marketing at 2-19 times that on drug research”

Wow drug research must be really cheap! To judge by the cretinous late-night ads for junk medicine. They can't have cost much to throw together...

I’ve always assumed the vast amount of marketing is the armies of incredibly high paid door to door salesmen who always seem to be visiting your doctor with some new pitch to reward them for prescribing their pet drug.

Its an interesting article.. I have questions!

This antibody binds to 'tissue factor' which are present at high levels on the surface of many cancer cells. Are these tissue factor present in significant proportions on other types of cell? (Reading later it suggests that side effects can include nose bleeds which I wonder if that means that nasal tissue also contains this)

The figures that they show; obviously it is a small cohort anyway and these people were otherwise considered untreatable but do we know what percentage of (eg) ovarian cancer would otherwise find that their tumors were either shrinking or had stopped growing? It would be important to compare that against the 14% they saw..

The mechanism of action is good, I am not able to say if it is novel (the name they use for the technique relates to an incident ~4000 years ago); do we have leads on other particular circumstances which may be useful to do this? (eg prostate cancer was not affected.. presumably because it has no tissue factor on its surface? could it identifiable by any other means?)

> This antibody binds to 'tissue factor' which are present at high levels on the surface of many cancer cells. Are these tissue factor present in significant proportions on other types of cell?

Tissue factor is expressed on the surface of the cells adjacent to blood vessels, so it's all over the body.

Tissue factor's normal role is to trigger blood coagulation - it reacts with factors in the blood to trigger a coagulation cascade. There is a waterproof layer of endothelial cells between the adjacent TF-bearing cells and the blood itself, so this only happens when a blood vessel is breached by mechanical damage, letting blood come into contact with TF - the resulting coagulation seals the breach. It's a cool system! Although a bit complicated:

https://diapharma.com/coagulation/

I had no idea there was a connection between coagulation and cancer, but apparently there is - specifically, it's involved in metastasis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151023/

The title ("‘Trojan horse’ drug treated British patients with six different forms of cancer") mislead me into imaging a cocktail of cancer cells as a treatment.

I thought they had 6 different cancers and thought that’s Super unlucky.

It's interesting that they mention specifically cervical cancer and head/neck cancers as some of the more successfully treated tumors, given that HPV is now thought to be a frequent cause of both.

7 February 2019 Lancet paper on Tisotumab vedotin trial here : https://www.thelancet.com/journals/lanonc/article/PIIS1470-2... (entitled: "Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1–2 trial")

Tisotumab vedotin is a first-in-human antibody–drug conjugate that is directed against tissue factor expressed on the cell surface of tumour cells to deliver a clinically validated toxic payload to tumours. [...] Tisotumab vedotin is comprised of a fully human monoclonal antibody specific for tissue factor conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable valine-citrulline linker. .... The study was funded by Danish and US biotech companies Genmab and Seattle Genetics

This Lancet paper references this 2014 Cancer Research paper: https://www.ncbi.nlm.nih.gov/pubmed/24371232?dopt=Abstract (http://cancerres.aacrjournals.org/content/74/4/1214.long) : "An Antibody–Drug Conjugate That Targets Tissue Factor Exhibits Potent Therapeutic Activity against a Broad Range of Solid Tumors"

Seattle Genetics page on Tisotumab Vedotin : http://www.seattlegenetics.com/pipeline/tisotumab-vedotin

Our [antibody-drug conjugate] technology combines the specificity of monoclonal antibodies, innovative linker systems, and the cell killing power of potent cytotoxic agents to treat cancer.

Interestingly, Seattle Genetics stock is down 12% on Friday: https://finance.yahoo.com/quote/SGEN ("cuz earnings"). Genmab was up 0.69% : https://finance.yahoo.com/quote/GEN.CO

Let's stop using the word "cancer" and split it in technical terms: https://www.lesswrong.com/posts/hwi8JQjspnMWyWs4g/resist-the...

I have no frame of reference, is 25% ish success rate a good thing?

Success rates in cancer are usually broken down by type of response (complete, partial, no growth, no response) and stage. It would have been helpful for the article to say what stage was being treated and compare the response rates in that stage to the best available treatment. For some cancers, 80-100% rate of complete response is currently achievable. Some are at 0%.

>their illness was well advanced and considered untreatable

Seems the 25% is up from a perceived 0% possible success rate.

The site seems deliberately designed to break safari when using a built in iOS content blockers. It’s like it reloads itself until the ads have loaded, making it impossible to scroll. Does anyone else see this? Is this a thing now?

Have the same experience, does anyone have a better source?

Looks like a problem with iOS content blocker, not the site, since I block ads aggressively and have no issue in Firefox on Android.

You can tap the share button and then Create PDF. Or, hold down the reader mode.

Same problem with Brave on Android (Galaxy Tab E).

When you see that it tries to reload, all you have to do is hit the stop button in the url to prevent it from reloading.

Same with Blokada on Android.

Seemingly. It doesn't hurt their SEO (like ajaxing in the content would) and "forces" people to turn off blockers. Or clear out.

This sort of dickery just means we'll see a rise in NoScript users, or that functionality becoming baked in.

Way too many advertising strategies are dangerously short sighted. That‘s what led to the proliferation of ad blockers in the first place.

Brave on Android had the same issue - toggling scripts to off via the brave icon made the site work perfectly.

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