Sm04554

[Occulus]

Dude - this is the first hair loss drug that is poised to move into a Phase 3 trial in almost 20 years. Not a bad thing.

Agreed - this is very promising. Also, the study cohorts were all NW 4s or higher, so those with less severe loss could see even better results. This is very exciting, and seems to be the closest to commercialization of all the current crop of pipeline drugs.

[lifelonglearning]

LOL to all of this

...

http://www.prnewswire.com/news-releases/samumed-announces-increases-in-both-hair-count-and-hair-density-observed-in-its-phase-ii-study-for-a-potential-treatment-of-androgenetic-alopecia-aga-300188222.html

"anotha one"

[trunks]

Samumed patent

There are few formulas of diketones in there. One of them is sm04554.

The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells

Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal development and homeostasis there is reciprocal activation of the androgen receptor (AR) and β-catenin in cells of the HF bulb. AR activation reduced β-catenin-dependent transcription, blocked β-catenin-induced induction of HF growth, and prevented β-catenin-mediated conversion of SGs into HFs. Conversely, AR inhibition enhanced the effects of β-catenin activation, promoting HF proliferation and differentiation, culminating in the formation of benign HF tumors and a complete loss of SG identity. We conclude that AR signaling has a key role in epidermal stem cell fate selection by modulating responses to β-catenin in adult mouse skin

Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia.

BACKGROUND:
Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells.
OBJECTIVES:
To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells.
METHODS:
HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens.
RESULTS:
In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.
CONCLUSIONS:
These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

[trunks]

And Samumed is the only company which tests drugs on >NW4 men.

[xyz123]

And how do you now that? They haven't even presented their phase II results yet...

If you follow the link:

"Samumed, LLC, a leader in tissue regeneration, announced today preliminary analysis of efficacy data from its Phase II AGA trial, in which one of the dosage arms, compared to vehicle, showed statistically significant increases for both objective outcome measures: non-vellus hair count (a primary outcome measures) and hair density (a secondary outcome measures), using the pre-specified statistical model."

“The Phase II safety and efficacy data so far are very promising and support moving this program into pivotal studies. We are analyzing the efficacy data further and plan to present results of both preclinical and clinical studies at upcoming medical conferences,” said Yusuf Yazici, M.D., Chief Medical Officer of Samumed."

[TooMuchHairWontKillYou]

Hope statistically significant means visually significant :d

[burtandernie]

Agreed - this is very promising. Also, the study cohorts were all NW 4s or higher, so those with less severe loss could see even better results. This is very exciting, and seems to be the closest to commercialization of all the current crop of pipeline drugs.

If this is closest to coming out how long are we talking? That is really the big issue is the timelines.

[breakbot]

If this is closest to coming out how long are we talking? That is really the big issue is the timelines.

Two years.

[ShookOnes]

If this is closest to coming out how long are we talking? That is really the big issue is the timelines.

Phase 3 to commercialization? 5 years

[Follisket]

And most importantly, how the hell do we figure out what they're using so we can get some black market production going and actually benefit from this?

[champpy]

Hope statistically significant means visually significant :d

Imagine if they had said 'dramatically significant', we would all be popping a cork right now

[Occulus]

Two years.

Two - three years to finish and report stage III results, so we'd know if it works (and how well) by then.

Phase 3 to commercialization? 5 years

Yeah, I'd guess four to five before it was available. Of course, if the stage III results were good, people would buy it counterfeit as soon as the Chinese started knocking it off.

[xyz123]

Imagine if they had said 'dramatically significant', we would all be popping a cork right now

Agreed - tough to know the relevance of statistically significant. A gain in 10 hairs versus a loss of 4 hairs could be statistically significant, though would be cosmetically irrelevant.

I also worry that they indicate that "one of the dosage arms" showed benefit - does this mean that the other dose of SM compared to placebo showed no benefit? If this is truly going to be an effective therapy - it's hard to believe that a difference of 0.1% (they were comparing 0.15% vs 0.25% vs placebo) would be a game changer.

Tough to know what it all means. It's also interesting that the treatment durations for these studies is so short. Phase 1 was 2 weeks and now Phase 2 was 3 months with an additional 45 day follow-up after treatment had stopped. Maybe they've been concerned about safety and are gradually giving increasing exposures? If it does regenerate new follicles, maybe 1 year (or indefinite) would provide greater regrowth (maybe that will be the approach in Phase 3?).

Regardless - this is all just worthless speculation...

That said - it certainly is nice that Samumed appears to be releasing information as it becomes available, in contrast to Allergan and bimatoprost.

Samumed aren't idiots - so if they're going to move forward with Phase 3, they'll presumably have reason to believe that it will provide satisfactory cosmetic regrowth. No one is going to go to their doctor and pay good money to go from a diffuse Norwood 4 to a mildly less diffuse Norwood 4.

[Joker]

Just replying to the above (in the unlikely event any SM reps or other companies ever stumble upon this comment) -- I think A LOT of people would pay A LOT of money to use a topical treatment with no systemic side effects in order to merely maintain their hair (with no regrowth whatsoever). So even modest regrowth on a NW6 translates to excellent maintenance for all other hair loss sufferers.

Also, I agree w/ respect to the "one dosage arm" language. However, it is possible that there is a threshold quantity of the drug that needs to be applied (somewhere between .15 and .25) in order to see efficacy. Of course, this logic goes out the window if only the lowest dose arm saw efficacy (which would be very odd and interesting).

[Tenma]

They are talking about "promising results" and "consistent with preclinical models".

Restoration of B-catenin signaling leads to regrowth on mice. That means they are growing new hair on humans.

I think they have something of value, it make no sense to spend millions in long and tedious phase 3 trial just to offer yet another maintenance treatment or something like minox, which only cuts for 1/3 people.