SM04554 Phase 2 results

[buckthorn]

What is this graph??? So, the placebo increased initially? Apparently, minoxidil completely loses effectiveness after two years?? The untreated group gained hair after two years? Am I reading this wrong?

 

[youngkidwithhairloss]

This would be gene therapy... years and years away. Way too much ethical concern as well, especially for a "cosmetic issue"... We need something like RU on steroids, haha... that will just bind with immense affinity and not let go.

Yeah RU on steroids would be great in the meantime, RU maintaining on dutasteride and RU? lol I know i'm lame

 

[Follisket]

Why can't anyone just do a modern take on Minoxidil without the sides and with it working on most people?
It seems that anyone just doesn't understand the mechanics behind it.

Why can't anyone just do a modern take on Propecia without the sides for that matter? Half of us wouldn't even have to waste a single thought on regrowth if we had that. I mean, it's ridiculous; I bet once a solid maintenance drug is out, the science behind it will seem laughably simple and people will wonder how it even took this long - though it'll be too late for us by then. Like, we literally already know how to freaking stop this hellspawn of a deformity, it's just that no one can be bothered to develop a drug that would do it safely, without wrecking our balls and sexuality. Partly because they're too busy wanking off to their cute, edgy little theories.

when this comes to market, you are in camp a too

Yeah, that's exactly it. My hair loss is recent enough that any one of these treatments would probably regrow enough hair - right now -
yet I still consider myself beyond saving simply because by the time they come out, I fear I will be.

follisket, because of your avatar, I read all your posts in an Eeyore voice in my mind...
is this accurate?

Hahah, well, as long as it's not Pooh! But yeah, guess I might as well own up to my melancholy.

 

[Swoop]

What is this graph??? So, the placebo increased initially? Apparently, minoxidil completely loses effectiveness after two years?? The untreated group gained hair after two years? Am I reading this wrong?

Well hypothetically it could be that a placebo treatment group gets increased hair growth. I have seen this before for instance in the AAPE treatment study vs placebo, where placebo got like 4% increase. As mentioned telogen hair follicles are sensitive to environmental stimuli so in pure sense even a placebo vehicle could possibly shift your hair cycle. And minoxidil was dropped after two years in that one graph by the way. But I agree with you that the placebo seems way too far fetched and the untreated group is weird, thus I account for error and possible bias in the studies and would personally tone these numbers (significantly) down. But even then SM has much work to do. I highly doubt that SM is going to perform much better on a longer time frame, but we'll see.

Price VH. Treatment of hair loss. N Engl J Med 1999;341:964-973

See also Price VH, Menefee E, Strauss PC. Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment. J Am Acad Dermatol 1999;41:717-721.

The treatments appear to induce a consistent increased growth offset (above placebo or untreated groups) of roughly 25% for the 2% minoxidil treatment and 35% for the 5% minoxidil treatment, an average increase of about 30%, maintained during the 96 weeks of treatment

 

[SriHanuman]

Swoop, only trials I found have data after 6 months of usage and results are somewhere around +21 and +18; bimatoprost and cb-03-01. If you have other clinical data, then please share.

 

[nameless]

Well hypothetically it could be that a placebo treatment group gets increased hair growth. I have seen this before for instance in the AAPE treatment study vs placebo, where placebo got like 4% increase. As mentioned telogen hair follicles are sensitive to environmental stimuli so in pure sense even a placebo vehicle could possibly shift your hair cycle. And minoxidil was dropped after two years in that one graph by the way. But I agree with you that the placebo seems way too far fetched and the untreated group is weird, thus I account for error and possible bias in the studies and would personally tone these numbers (significantly) down. But even then SM has much work to do. I highly doubt that SM is going to perform much better on a longer time frame, but we'll see.

Swoop, have you given much thoughy into Kerastem? This looks potentially groundbreaking.

Check this out Swoop, when doctors inject ADSCs by themselves those cells migrate out of the injected area rapidly so Kerastem uses ADSCs but it puts them
inside of their own new fat tissue called "puregraft" which purportedly has a high degree of long term retention.

AAPE and Histogen both only treat your follicles to the appropriate growth factors at the time of injection but it looks like Kerastem might get the same growth
factors to your follicles on a more regular basis since the actual fat that is laid down produces the growth factors (inside of AAPE and Histogen) and emits them
to your follicles on a more regular basis, just like before your hair loss started when your scalp's fat layer was thicker.

What do you think about this?

- - - Updated - - -

I guess that Kerastem is this stuff http://www.puregraft.com/ combined with ADSCs.

 

[Swoop]

@Sri, what the trials of minoxidil you mean?

@Buckthorn to underscore this even more I remembered this study to have the same, check at latanoprost vs placebo;

At 24 weeks at the latanoprost-treated site, the density (22% in the entire study population) was significantly higher compared with baseline and placebo. As vellus hairs increased on both investigational sites, the vehicle may also have stimulated hair growth. This has also been reported in topical minoxidil studies. Still, the increase on the placebo-treated site was nonsignificant (1.2%, P = .3) compared with the latanoprosttreated site (3.5%, P = .05).

Bottom line is from this, modulation of the hair follicle cycle is pretty easy. Many things can do this ranging from growth factors, trauma (hair transplant temporary shock loss), to immunosuppresive drugs (cyclosporine, tacromilus). The art is not in doing that, the art is to completely revive these really (unhealthy) miniaturized hair follicles that are arrested (for instance on a completely bald temple area).. A very hard job as we all know.

@Nameless, some more evidence, pictures or studies would be great.

 

[thinning44]

People are speculating that SM needs to go back to Phase I, but I haven't seen anything from the data in the Forbes article or their own previous statements that would indicate they plan to start over.

Also, if you were in charge of figuring out how best to structure and budget the Phase 2 trial for this drug, would you have gone for the longest Phase 2 possible or the shortest? The longer a trial runs, the more it costs per patient and the more money the company burns keeping its doors open and paying employees in the interim. Obviously there are trade-offs - a longer trial might show better cumulative results for hair growth which might make getting the funds to run the trials easier. That said, if you think the drug works wouldn't you go for a Phase 2 trial that you believe would be just long enough to show positive results and interest investors, but not so long as to waste time and money? Seems to me it'd be stupid to run a Phase 2 with 1 year of treatment if you didn't need to, and it looks like they didn't need to. They saw about 10% growth in 90 days, with good safety. Now they can move on to Phase 3 without having wasted millions of dollars and an extra 9 months of time. Seems clever to me.

My guess would be for Phase 3 FDA will probably demand a longer trial as they probably assume people will want to use the drug for longer than 90 days and they need to see the safety data to match.

 

[nameless]

I think that this Kerastem (if they do it as Washniek said in his interview) might be the cure. I suspect that so far
the company has probably only laid down a VERY thin layer of new fat because they're probably antsy about doing
a new treatment on people. But I think they could probably be talked into doing a slightly thicker layer of their new
fat + ADSCs and I think this would have a lot more potential than anything else we're talking about. It should blow
Histogen out of the water because it would get the same growth factors Histogen does into the scalp but it would do
so on a more regular basis.

 

[SriHanuman]

Swoop I meant these two results from trials:
https://clinicaltrials.gov/ct2/show...0156&term=minoxidil&rslt=With&rank=3#outcome1
http://www.cassiopea.com/~/media/Files/C/Cassiopea/presentations/2015-financial-results-v2.pdf

Which show that minoxidil produces around +20/cm2 in 6 months. Now, I am interested at minoxidil results after 3 months, are there any numbers from clinical trials? Not some graph, from somewhere, but proper clinical trials. I can not find any, you said something along the lines "google it" there are.

 

[buckthorn]

I think that this Kerastem (if they do it as Washniek said in his interview) might be the cure. I suspect that so far
the company has probably only laid down a VERY thin layer of new fat because they're probably antsy about doing
a new treatment on people. But I think they could probably be talked into doing a slightly thicker layer of their new
fat + ADSCs and I think this would have a lot more potential than anything else we're talking about. It should blow
Histogen out of the water because it would get the same growth factors Histogen does into the scalp but it would do
so on a more regular basis.

After researching this more thoroughly, i agree, it does sound very promising. The question is... how do we do it ourselves? haha :banned:

 

[Swoop]

Swoop I meant these two results from trials:
https://clinicaltrials.gov/ct2/show...0156&term=minoxidil&rslt=With&rank=3#outcome1
http://www.cassiopea.com/~/media/Files/C/Cassiopea/presentations/2015-financial-results-v2.pdf

Which show that minoxidil produces around +20/cm2 in 6 months. Now, I am interested at minoxidil results after 3 months, are there any numbers from clinical trials? Not some graph, from somewhere, but proper clinical trials. I can not find any, you said something along the lines "google it" there are.

They are two different graphs the 96 weeks graph is from a low N=; http://vipadenievolos.ru/files/rese..._application_of_5_and_2_topical_minoxidil.pdf.

The other one is from Olsen who has done different minoxidil studies including a 5 year follow-up somewhere in the 90's. But the 48 week one is from this study from Olsen

2002 clinical trial; https://www.researchgate.net/public...the_treatment_of_androgenetic_alopecia_in_men

Next time google please .

 

[nameless]

After researching this more thoroughly, i agree, it does sound very promising. The question is... how do we do it ourselves? haha :banned:

We can't do it ourselves. We have to move past that idea. The best we might be able to do is form a group of customers and ask for a group-rate discount.

 

[SriHanuman]

They are two different graphs the 96 weeks graph is from a low N=; http://vipadenievolos.ru/files/rese..._application_of_5_and_2_topical_minoxidil.pdf.

The other one is from Olsen who has done different minoxidil studies including a 5 year follow-up somewhere in the 90's. But the 48 week one is from this study from Olsen;

2002 clinical trial; https://www.researchgate.net/public...the_treatment_of_androgenetic_alopecia_in_men

Next time google please .

I still see 12 weeks results only from the first link, where untreated group also had around +10, which is peculiar to say the least. So it is impossible to compare it with SM04554, that was my point. Your comparison was rash and emotional, but hey, I give up

 

[Swoop]

Graph link just clipped hair, put them on the grid and counted them. So not only terminal hair?
Last link has results after 12 months not 3, so let say next time read please; we are talking about 12 weeks. So it is impossible to compare it with SM04554, that was my point. So your comparison was rash and emotional, but hey, I give up

I had troubles understanding you, thought you meant a longer period than 3 months. Indeed 3 months and 16 weeks is not the same but the 8 week data is also present. I even said I account for study error and bias and correction of other studies and would put minoxidil more at around the 20% mark. Also 1 month of a difference shouldn't do much really. What is important that SM doesn't match minoxidil and if it won't match minoxidil it will never reach the market as much as we would like it to do. It actually needs to perform better, not only be the same. Or do you think otherwise?

We can only wait, time will tell .

 

[nameless]

I had troubles understanding you, thought you meant a longer period than 3 months. Indeed 3 months and 16 weeks is not the same but the 8 week data is also present. I even said I account for study error and bias and correction of other studies and would put minoxidil more at around the 20% mark. Also 1 month of a difference shouldn't do much really. What is important that SM doesn't match minoxidil and if it won't match minoxidil it will never reach the market as much as we would like it to do. It actually needs to perform better, not only be the same. Or do you think otherwise?

We can only wait, time will tell .

I wasn't going to get involved in this debate because so far I'm disappointed in the numbers put out by Samumed. However, you guys are comparing medicines that work by different modes of action and that makes it hard to draw conclusions about which one is better since the test subjects only used the treatment for 3 months in the last study. It would be possible for one treatment to start out slower and then overtake the other treatment as time goes on since they work by different modes of action. One treatment might cause regrowth of just 10% every 3 months but continue on that path compounding another 10% every 3 months for 2 years so ultimately the person would get full reversal whereas the other treatment might have a limited ceiling as far as how much hair the patient could recover. Also, one treatment might work on everyone whereas the other treatment might only work on a comparatively small % of patients. We need more information about this last study and we need to see patients apply SM04554 for longer periods of time.

That having been said, Kerastem looks more promising anyway.

 

[SriHanuman]

I had troubles understanding you, thought you meant a longer period than 3 months. Indeed 3 months and 16 weeks is not the same but the 8 week data is also present. I even said I account for study error and bias and correction of other studies and would put minoxidil more at around the 20% mark. Also 1 month of a difference shouldn't do much really. What is important that SM doesn't match minoxidil and if it won't match minoxidil it will never reach the market as much as we would like it to do. It actually needs to perform better, not only be the same. Or do you think otherwise?

We can only wait, time will tell .

Finally we agree, time will tell. Lots of known unknowns, like does it work on temple region, in what % of people does it work, what happens after 4-5-6 months, etc. etc.. So, lets wait and hope for the best.

And yes, I think otherwise. If after 6 months it matches minoxidil, and it works on slick bald, high norwoods, even on temple regions, on lets say 80% of people, great safety profile... People would buy it over minoxidil even with a higher price involved. This is just speculation. Let's wait and not be rash as we do not have all the data; I would really like to see a picture of the best and the worst performer in these trials.

 

[TheShining]

10 new hairs on a patch of 100 hairs = 10% regrowth.

I know I am beeing naive, but I try to stay positive. We dont know the time frame for this 10% increase or if the hair count keap increasing after this time.
But if it lets say increases by 10% every 3 months, you will double your number of hairs in less than 8 repetitoins of 3 months (1,1 ^ 8)

 

[Dench57]

The only thing important to me is whether this increased hair count can be maintained in the presence of DHT basically. Minoxidil is a band aid, buying yourself time, fighting against the tide of androgens, that will eventually lose. If it's "just another" growth stimulant then it needs to be significantly outperforming, or at the very least matching Minoxidil, which it doesn't seem to be doing. So why would it go to Phase 3? What use is there in this product?

3 months is obviously too short of a time to conclude much but I was under the impression that WNT signalling, in laymans terms, was basically to kick start growth i.e nothing to shield against DHT/PGD2 and miniaturizing follicles. So a growth stimulant, rather than a protective treatment.

 

[nameless]

The only thing important to me is whether this increased hair count can be maintained in the presence of DHT basically. Minoxidil is a band aid, buying yourself time, fighting against the tide of androgens, that will eventually lose. If it's "just another" growth stimulant then it needs to be significantly outperforming, or at the very least matching Minoxidil, which it doesn't seem to be doing. So why would it go to Phase 3? What use is there in this product?

3 months is obviously too short of a time to conclude much but I was under the impression that WNT signalling, in laymans terms, was basically to kick start growth i.e nothing to shield against DHT/PGD2 and miniaturizing follicles. So a growth stimulant, rather than a protective treatment.

Yea but Dench what if WNT somehow protects follicles by fighting off DHT? And what if the amount of WNT your body naturally produces declines over time? If that is the case then
stimulating WNT could solve the problem by bringing your WNT back up to a level that it could fight off DHT right? And then it wouldn't matter if your body still produced DHT right?