This study assess the efficacy and safety of a new formulation of DMF (LAS41008) compared with placebo and Fumaderm in adults with psoriasis.

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Background:
Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.

Objectives:
To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm®, in adults with moderate-to-severe chronic plaque psoriasis.

Methods:
In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of ‘clear’ or ‘almost clear’ in the Physician's Global Assessment (PGA) at week 16.

Results:
In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm®; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm®: P < 0·001). Overall, 33% of patients treated with LAS41008 were ‘clear’ or ‘almost clear’ in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm®. Most treatment-related adverse events were classed as ‘mild’ in severity.

Conclusions:
LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.

Source: onlinelibrary.wiley.com

*Funding: Almirall

Its great to know there's a new formulation of DMF at a phase 3 trial stage and it is performing well ( but not quite as well as Fumaderm) there is a big market out there in America and the rest of the world that up to now haven't got a DMF drug available....hopefully when this drug gets approval,  DMF will get more press and get widely used ....instead of the current first line treatment

Ah, this is the one from Almirall.
Advantage of this version is that no MEF is involved. This gives the possibility to go higher that 720 mg, just like Bill can do.
It's indeed good that there is a new player. I wonder what the effect will be on spreading and prices.

The fact that it seems to be better in the period of 16 weeks is because of MEF, it slightly enhances the responsiveness to DMF.
But on the longer term, in DMF terms 16 weeks is short, that difference will vanish. And than LAS41008 will have the advantage of being non toxic.
Nowhere is however being spoken about slow release.
It remains very obvious that a slow release version will be very less irritating for your intestines.

(Fri-17-03-2017, 17:29 PM)Caroline Wrote: The fact that it seems to be better in the period of 16 weeks is because of MEF, it slightly enhances the responsiveness to DMF.
But on the longer term, in DMF terms 16 weeks is short, that difference will vanish. And than LAS41008 will have the advantage of being non toxic.
Nowhere is however being spoken about slow release.
It remains very obvious that a slow release version will be very less irritating for your intestines.

I was surprised to see the clearance after 16 weeks and that Fumaderm at 37.4% outperformed LAS41008 at 33% if I'm reading it correctly
I hope they have got the slow release aspect covered ....it would make good sense

(Fri-17-03-2017, 17:42 PM)jiml Wrote:

(Fri-17-03-2017, 17:29 PM)Caroline Wrote: The fact that it seems to be better in the period of 16 weeks is because of MEF, it slightly enhances the responsiveness to DMF.
But on the longer term, in DMF terms 16 weeks is short, that difference will vanish. And than LAS41008 will have the advantage of being non toxic.
Nowhere is however being spoken about slow release.
It remains very obvious that a slow release version will be very less irritating for your intestines.

I was surprised to see the clearance after 16 weeks and that Fumaderm at 37.4% outperformed LAS41008 at 33% if I'm reading it correctly
I hope they have got the slow release aspect covered ....it would make good sense

Well Jim, that is a known effect of MEF. Nicolle Litjens mentioned it also in her promotion research.

It is a very small difference in efficacy.

Caroline, I know how much you like the slow release formulation, but I have had very good success reducing my GI upset with a few l-cysteine doses, and I have taken doses of up to five times the maximum DMF dose for Fumaderm. There is more than one way to skin a cat.

Cheers,

Bill

(Fri-17-03-2017, 20:42 PM)Bill Wrote: It is a very small difference in efficacy.

Caroline, I know how much you like the slow release formulation, but I have had very good success reducing my GI upset with a few l-cysteine doses, and I have taken doses of up to five times the maximum DMF dose for Fumaderm. There is more than one way to skin a cat.

Cheers,

Bill

Absolutely true Bill
I admire your approach, which is Very excellent. I mentioned your results to my doc, and he is very amazed by it.
You must admit that you are of a special kind, not many will follow your footsteps, but you are the living example of the possibilities of DMF.
Still i think that most other people will have to find a more conventional way. Fumaderm and Tecf*dera are mainstream, Netherlands Psorinovo is already quite off-stream even here in the Netherlands.
But your are way outside of the mainstream, unsellable to most of us.

Cheers,

Caroline

Thanks, Caroline. Given the variety of responses, I think that dmf needs to be tailored to the patient. L-cysteine has made a very substantial difference with dmf gut irritation for me, and I dont think it my imagination. Yes, I am stubborn and persistent, but I think my current approach to be very simple, safe and effective. I would like to see the regime tested, but not by d-i-yers. I suspect that twice weekly or thrice weekly dosing isn't more effective only for me.

Cheers,

Bill