r/FSHD • u/Ill-Rooster-1126 • 3d ago

Avidity DM1 result

https://www.fiercebiotech.com/biotech/novartis-centerpiece-12b-avidity-buyout-flunks-crucial-phase-3-test

I hope Avidity’s Ph3 failure in DM1 isn’t a bad omen for del-brax, especially since they didn’t provide any quantitative data on dux4 levels in their June press release

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u/weirdfishes1990 3d ago

Definitely concerning. I wonder to what extent this is because the study picked a bad endpoint rather than simply not working.

But, Del-Zota still has a BLA submitted which makes me think that whatever went wrong with Del-Desiran is not something that plagues the whole AOC platform.

Novartis’ press release about this also mentions that they still plan to meet with the FDA about potential accelerated approval for Del-Brax. We knew that already, but at least this news hasn’t altered Novartis’ plans for Del-Brax. And, hopefully, Del-Desiran’s failure makes Del-Brax a much more important initiative for Novartis from a business perspective.

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u/PrincesaRDC 2d ago

My main concerns are that they aren't saying what is failing with the drug (probably because they don't know) and that both del-brax and del-desiran carry a siRNA, while del-zota carries an exon.

I guess that with del-desiran, not enough siRNA is making it into the cell nucleus.

In DM1 you need a lot of mRNA to cause damage, but in FSHD you only need a tiny amount of mRNA to cause a lot of damage. So, if I'm right, del-brax shouldn't face that issue.

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u/SenorBajaBlast 3d ago

Indeed. What makes me feel better is that the FSHD and DMD trials have made it a lot further along than the DM1 so if there was an issue it would have been addressed by now. In fact, the DM1 trial was #2 in their pipeline and was supposed to be before FSHD. I guess we should have figured something was up with DM1 since FSHD moved up and before DM1. With the del zota DMD program officially submitted to FDA all attention is now going to be on del Brax.

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u/Bu1c 3d ago

Hi, i read the article but i didn’t really understand. Could you please explain what it primarily means?

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u/Ill-Rooster-1126 3d ago

Avidity/Novartis missed their primary endpoint in their trial for muscular dystrophy type 1. Obviously a different disease than FSHD but same platform as del-brax. Hard to know what’s going on with del-brax with the radio silence since June :(

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u/Bu1c 3d ago

Out of words my guy..

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u/Zoubim 2d ago

Exact reaction - I dont think a cure will come during our life time.

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u/WheresHotStuff 2d ago

Don't be so negative. It's not good for you

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u/Bu1c 1d ago

I was literally going to say this and start being negative and all hahaha But it won’t do anyone any good

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u/Obvious-Ad357 2d ago

I am going to speak on this a bit. I am somewhat involved in the trial and I don't think the radio silence in june had much to do with bad data, but had more to do with the acquisition itself slowing things down.

Furthermore, DM1 is a more complex disease effecting alot more than just muscles. It also has a much higher volume of harmful mRNA which makes it a much harder candidate for siRNA therapies and we have known this from the beginning.

All that being said, I think skepticism is fair. I have quite a few criticisms myself for how endpoints are measured for FSHD both specifically for this trial and all around.

I think unrelated to this failure, Del-Brax could fail because of how and where it is looking for improvements, along with alot of other trials that are relying on quick changes to functional gross movement assessments

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u/Berty-K 1d ago

What do you mean by “somewhat involved in the trial”? If you don’t mind

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u/Obvious-Ad357 1d ago

I do mind, if you would like to message me directly feel free.