Sm04554

[lacazette]

Agreed Xyz, it makes sense.

And the fact that Samumed is a small company, nor a hair company, but still is the third biggest sponsor of the hair congress makes me optimistic.

the VPA human trial confirmed that Bcatenin pathway activation give results

the question is how far they can go with that bcatenin pathway upregulation without playing with cancer risks

little activation will help to slow the AGA processus
medium activation could rstrongly slow the process for years, (or even stop further hairloss) and rescued the follicles that are in the beginning process of miniaturization
high activation lead to ectopic HF formation from existing ones (and then even a nw7 could come back on the Norwood scale after years of application ^^)

fingers crossed

[xyz123]

the question is how far they can go with that bcatenin pathway upregulation without playing with cancer risks

little activation will help to slow the AGA processus
medium activation could rstrongly slow the process for years, (or even stop further hairloss) and rescued the follicles that are in the beginning process of miniaturization
high activation lead to ectopic HF formation from existing ones (and then even a nw7 could come back on the Norwood scale after years of application ^^)

fingers crossed

Lacazette - I think it's got to be the last one. Their inclusion criteria were NW 4-6 - so maintenance is not a reasonable goal (no one is going to pay for and apply a topical cream daily to remain a NW6). And the endpoints in their trials (particularly the new one) is change in hair counts - this is not geared towards maintenance - especially with a 3 month follow-up - you wouldn't see anything. And I really think the scalp biopsies are being done to look for follicular neogenesis - you can't prove that with visual inspection, but you can with pre-/post-scalp biopsies.

And their new trial only has a target enrollment of 50 people. When you have a weak treatment for regrowth, you need to enroll a large number in order to show statistical significance (i.e. 1000 patients for the Propecia trials) - and for maintenance, you need to follow for years. When you have a dramatic treatment that works quickly (i.e. lots of regrowth), you only need a handful of people for a short period of time to show benefit.

This second phase 2 trial - driven by the results of the first Phase 2 trial - is definitely going to be positive (they know exactly what's going to happen based on the identical protocol that they ran in the first trial). So with 50 people split into 3 treatment arms, they are going to show an increase in terminal hairs in just 3 months.

This really may be the answer for many of us. If the results are great, I have to believe they'll be presented in Miami. And if they are, Samumed deserves to turn into a multi-billion dollar company. Here's to California Biotech - you stay classy San Diego

[maver1ck]

Hey all. First time caller long time listener. Been following this thread very closely and I appreciate all the insight being given here. I also have high hopes for SM04554 but what I really want to know is how quickly this would be taken to market given the supposed efficacy and the emergence of the 21st century cares act. Are we looking at 1-2 years max? Or something more along the lines of 4-5?

[xyz123]

Hey all. First time caller long time listener. Been following this thread very closely and I appreciate all the insight being given here. I also have high hopes for SM04554 but what I really want to know is how quickly this would be taken to market given the supposed efficacy and the emergence of the 21st century cares act. Are we looking at 1-2 years max? Or something more along the lines of 4-5?

Pure speculation - but I would guess 1-3 year range.

If the 21st century cures act passes and applies to this drug, I think it could come to market in late 2016.

If the FDA still requires a Phase 3 trial, I think it will be 2018. The Phase 3 trial will start in mid to late 2016 (there won't be delays - assuming the drug works, everyone and their grandmother will want to invest in this company), will last ~ 1 year, and then the FDA review will take 3-9 months.

That's my guess. No way it takes 5 years if the drug truly works like we hope/think it will.

[Dimoxynil]

Pure speculation - but I would guess 1-3 year range.

If the 21st century cures act passes and applies to this drug, I think it could come to market in late 2016.

If the FDA still requires a Phase 3 trial, I think it will be 2018. The Phase 3 trial will start in mid to late 2016 (there won't be delays - assuming the drug works, everyone and their grandmother will want to invest in this company), will last ~ 1 year, and then the FDA review will take 3-9 months.

That's my guess. No way it takes 5 years if the drug truly works like we hope/think it will.

Just one question ,

Is the only reason were getting excited because they're testing on higher end NW scale men?

If I was a cynic I would suspect that they would use higher NWs as false proof of maintainance. For example, most people loose hair more rapidly between NW 2-3 than say between 4-5. So would it not aid your results to use subjects whose hair loss is already progressed but no longer aggressive ? This would give you better looking results.

[xyz123]

Just one question ,

Is the only reason were getting excited because they're testing on higher end NW scale men?

If I was a cynic I would suspect that they would use higher NWs as false proof of maintainance. For example, most people loose hair more rapidly between NW 2-3 than say between 4-5. So would it not aid your results to use subjects whose hair loss is already progressed but no longer aggressive ? This would give you better looking results.

No. Both Phase 2 trials are randomized, double-blind, placebo controlled trials. The efficacy of both doses of SM are compared to placebo (ie. the vehicle alone). In the event that all study participants had completely stopped losing their hair, the drug would appear no better than vehicle alone - and hence the studies would be negative.

If the studies are positive, it means that the study participants receiving the real SM grew more hair than participants receiving placebo (vehicle alone) in just 3 months.

[Dimoxynil]

^
Cheers mate, excellent response

[nameless]

Agreed - though I don't think the battle is over after new hair follicles are created - the new follicles are unlikely to be 100% consistent with regular follicles - and there will be years of working on making them cosmetically acceptable, ensuring they regenerate after they fall out, and then there's the issue that they might be androgen sensitive and maintenance drugs will still be required...

That said - and to keep this thread on topic - after some more thought, I am 99% positive that the SM trial was positive - and believe it or not, this isn't just mental mast.rbation

I'm involved in clinical trials in another area of medicine (that actually gets NIH funding...) and just realized - you canNOT conduct a clinical trial in humans when you know that the result is going to be negative - i.e. the notion of FUTILITY.

When you do a study in humans with an experimental drug and the result is negative - you can't go back to the FDA and say - "yeah, the drug doesn't work - but we'd like to gather some more information to find out why. So would you mind if we ran another trial - it will just be another 50 people and this time we'll take scalp biopsies".

It doesn't work like that - with animals, there's no problem with giving an ineffective drug to another 50 mice to gather more data to try and understand why. But you can't do that with humans - to conduct another trial, you would have to change something about the protocol and provide justification why you think it will work this time (which usually means going back to the lab and generating additional data). And that's not the case here - the protocol for both of the SM Phase 2 trials are COMPLETELY IDENTICAL.

And from a common sense perspective - this also makes sense. Can you imagine getting informed consent for a patient when you know the drug doesn't work? "Yeah - we're running a study for hair loss. We just ran the same study and we know that the drug doesn't work. But we want to try and understand why, so this time we're going to take a piece of your scalp at the start and end of the study - that will hurt, but not that much. Oh - and by the way, although we know that the drug doesn't work, there's a small chance it could cause cancer. So... wanna sign up?". No way this happens.

The fact that they got permission from the FDA to run a second study means that the Data Safety Monitoring Board (DSMB) did an interim analysis of the study and found that the results were positive. They communicated this to the FDA (they're required to) and based on these results - either the FDA or the company or both - decided that they wanted to better understand the mechanism through which this drug worked, which triggered the second study.

The first trial has to be positive. SM works - believe it. The question now is to what extent...

I also do not believe that the FDA would allow a company to go on a fishing expedition on human beings to find out why a drug did not work. I could be wrong but I don't think so. And I do believe that the FDA would have been involved in setting up the additional phase 2 study and I think that the additional phase 2 study is probably set-up to get the company the necessary bio-markers to avoid a phase 3 trial.

[nameless]

Pure speculation - but I would guess 1-3 year range.

If the 21st century cures act passes and applies to this drug, I think it could come to market in late 2016.

If the FDA still requires a Phase 3 trial, I think it will be 2018. The Phase 3 trial will start in mid to late 2016 (there won't be delays - assuming the drug works, everyone and their grandmother will want to invest in this company), will last ~ 1 year, and then the FDA review will take 3-9 months.

That's my guess. No way it takes 5 years if the drug truly works like we hope/think it will.

How can we invest in this company?

I think there will be a minimum amount that you have to invest. For example, a person might have to invest at least $25,000 or $50,000 or something like that. I don't happen to have that kind of money sitting around.

Perhaps we could form a group of us to each put in a certain amount of money so that we can collectively reach the minimum amount needed to invest.

[nameless]

Just one question ,

Is the only reason were getting excited because they're testing on higher end NW scale men?

If I was a cynic I would suspect that they would use higher NWs as false proof of maintainance. For example, most people loose hair more rapidly between NW 2-3 than say between 4-5. So would it not aid your results to use subjects whose hair loss is already progressed but no longer aggressive ? This would give you better looking results.

I really don't think so.

[joel203]

would SM work for maintenance as well as regrowth?

[nameless]

would SM work for maintenance as well as regrowth?

How are we supposed to know the answer to this question with certainty? We are not company spokespersons.

[JayM]

If it works, yes.

[nameless]

Damn! you are right my friend, it's a clear possibility

I wasn't aware of that! I was believing that elimination of phase 3 would be ONLY for rare and serious diseases but I was wrong! thank you dude you made my day

its also said here :

http://www.collective-evolution.com/2015/07/07/the-21st-century-cures-act-is-on-its-way-heres-why-you-havent-heard-about-it/

"The 21st Century Cures Act allows drugs to be rushed to the market, removes phase 3 testing as a requirement for drug approval, bases drug approval on biomarkers rather than actual health outcomes"

And here:

http://www.raps.org/Regulatory-Focus/News/2015/04/30/21192/Regulatory-Explainer-The-Updated-21st-Century-Cures-Act/

Subtitle B of Title II is slightly modified from the original draft of the legislation. It remains focused on the "qualification and use of drug development Tools
"The development of biomarkers and other drug development tools can benefit the availability of new medical therapies by helping translate scientific discoveries into clinical applications," the bill explains

Section 2022 of the draft legislation would amend federal law to facilitate accelerated approvals—approvals based on surrogate (e.g. intermediate) endpoints intended to serve as evidence that a drug would be effective in a population. FDA has long relied on surrogate endpoints to support accelerated approvals, but only for drugs intended to treat patients with life-threatening illnesses and unmet needs.The legislation would require FDA and a sponsor to enter into an "accelerated approval development plan" (AADP) similar in concept to a special protocol assessment (SPA). The AADP would establish the minimum data parameters which, if met, would support the approval of a drug using surrogate endpoints.


And from your link:

"This part of the bill allows drugs to get to the consumer quicker. This is because Phase 3 testing has been eliminated
The new method replacing Phase 3 testing bases drug approvals on biomarkers, the way living cells react to specific things introduced to those cells


The real world effects of this Act are still unknown but the central point of contention is singularly rooted in the increased freedom and lack of oversight of pharmaceutical companies."


Sounds too good to be true x)
Im not aware of us, when do this bill will defenitly be adopted? Is there obstacles to come or can we say that it's just a matter of time?

On second thought I doubt if the FDA would allow a human study (putting
humans at risk) that would satisfy the requirements of a pending legal bill
that is not yet law.

[xyz123]

On second thought I doubt if the FDA would allow a human study (putting
humans at risk) that would satisfy the requirements of a pending legal bill
that is not yet law.

I'm sure neither side explicitly stated that was the reason for the second trial - but Samumed undoubtedly knows it's likely to be passed (industry/biotech is one of the major drivers for this act). So, in the event that it does get passed, why not run a relatively small and quick trial to acquire the necessary biomarker data that would lead to earlier approval. They're not really losing any time and the additional cost could be well worth it.

Given that the drug appears safe - and presumably effective - the FDA won't say no to this. More data in terms of patient outcomes and the drug's mechanism of action is never a bad thing. I'm sure the FDA would happily approve the trial on that basis (while at the same time, knowing in the back of their minds that the major reason Samumed probably wants the trial - although not explicitly stating it - is to potentially avoid a Phase 3 trial and pursue earlier approval in the event that the act is approved).