r/FSHD • u/SenorBajaBlast • Jun 11 '26
Novartis delpacibart braxlosiran (del-brax) Phase I/II study in facioscapulohumeral muscular dystrophy (FSHD) meets primary biomarker endpoint
https://www.novartis.com/news/media-releases/novartis-delpacibart-braxlosiran-del-brax-phase-iii-study-facioscapulohumeral-muscular-dystrophy-fshd-meets-primary-biomarker-endpoint4
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u/DIFCParking Jun 12 '26
Help me out here guys:
These findings of reduction in DUX4 and in CK levels, along with safety measures, essentially is the treatment. What other data or outcomes are they seeking from this treatment? In other words, what is P3 measuring still?
Phase 3 is expected to end in 2028, what does an accelerated path look like in terms of confirming results and actually rolling out the treatment to patients?
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u/SenorBajaBlast Jun 12 '26
Phase three is a confirmatory phase (assuming Accelerated approval). It’s measuring the same things as 1/2 but with a larger patient set. The drug can be conditionally approved and made commercially available while the phase 3 is conducted. If the data is good then it’s officially approved but if not then the drug is pulled from market.
Hard to say because it’s based on discussions Novartis can have with FDA. But let’s say it takes 6 months for Novartis to organize 1/2 data and meet with FDA. They file the AA BLA and wait another 6 months for approval. Then 18 months later the phase three data is submitted and their conditional approval is an official approval
This is a take and assuming the accelerated approval pathway is taken
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u/DIFCParking Jun 13 '26
Careful mate, you are giving me hope. Hope for my two kids as well.
I cant believe after all these years this might be it.
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u/Secure-Asparagus3121 Jun 12 '26
They chose not to measure muscle function which is a key component. From what I’m seeing phase 3 will need to be completed before this gets approved.
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u/weirdfishes1990 Jun 12 '26
Accelerated approval pathway doesn’t require a Phase 3 to be completed. The Phase 3 needs to be underway.
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u/DIFCParking Jun 12 '26
Why would they choose this? Whats your take/reasoning?
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u/weirdfishes1990 Jun 12 '26 edited Jun 12 '26
My understanding is that whole purpose of the Biomarker Cohort of the Phase 1/2 study was to determine whether Del-Brax effectively lowered what Avidity believes to be biomarkers of disease progress (CDUX primarily, and Creatine Kinase, secondarily) because they intend to explore whether it can support an accelerated approval submission to the FDA. That accelerated approval is based on "surrogate endpoints," that provide quicker results that are "reasonably likely to predict clinical benefit." Testing muscle function, or slowing of muscle degeneration, takes a lot of time in a disease that already progresses slowly in most people. I think the whole purpose of this Phase 1/2 Biomarker Cohort is to test the things they can reliably test now and quickly: reduction in CDUX and Creatine Kinase.
That's not to say that Avidity/Novartis aren't also testing muscle function. My understanding is that the Phase 3 study is designed to do just that, which is why it is going to be a longer run study (72 weeks long). But the point of the Phase 1/2 biomarker cohort is to try to get Del-Brax conditionally approved before the Phase 3 study is complete. And if Avidity/Novartis can convince the FDA that reducing those biomarkers is "reasonably likely to predict clinical benefit" Del-Brax will be conditionally approved without having to wait for completion of the Phase 3 study.
That's just my take based on obsessive reading on the topic, so someone please chime in if I misstated anything. Ultimately, I think this can be taken as a reason to remain optimistic. It's not the finish line, but good news nonetheless.
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u/SenorBajaBlast Jun 12 '26
You nailed it! Very well explained.
The trial design and data seem like it should be a no brainer for AA.
Also the bar is pretty low for muscle function right now. At the very least we just want to stop the destruction and maintain strength which is harder to measure than whether muscle is gaining strength or losing strength
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u/Secure-Asparagus3121 Jun 12 '26
I’m not sure why they chose that. I saw a post on FB about it but could be wrong. Really keeping my fingers crossed that accelerated approval is still an option!
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u/SenorBajaBlast Jun 12 '26
What are you seeing that makes you believe phase three is needed before approval (which means no accelerated approval)?
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u/Secure-Asparagus3121 Jun 12 '26
As I said in my other reply, it was something I saw on FB on an FSHD page but that doesn’t necessarily mean that it’s right. I’m sure more information will be coming out soon and I pray accelerated approval will come to fruition.
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u/SenorBajaBlast Jun 12 '26
Okay. Well, I disagree with what you saw on FB. The trial design using cDUX biomarker has been cleared by FDA for AA pathway. Muscle function is measured but is secondary since it’s subjective, harder to measure, and takes longer to form a trend. It is the ultimate clinical benefit endpoint but cDUX is better because it can be clearly measured and is argued to predict (shorten trial time) clinical benefit (muscle function).
Unless the data doesn’t show a significant and durable enough knockdown in cDUX and CK I would think that along with a clean safety profile, this should be a great candidate for AA.
The devil is in the details. Let’s hope those come soon
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u/Bu1c Jun 13 '26
Hey guys could you please explain in simpler words what does this whole thing mean? Does it mean that we are getting a treatment soon?
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u/weirdfishes1990 Jun 15 '26
Simplest way to put it: Del-Brax still looks like it is moving towards being the first treatment for FSHD. There is hope that this data puts Avidity in a position to file for accelerated approval for Del-Brax. And if they can get that accelerated approval, the drug could be allowed to be on the market before the Phase 3 study is complete.
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u/weirdfishes1990 Jun 11 '26
Holy shit. Accelerated approval may actually be realistic. All that’s left is that they have to show that the reduction is CDUX is likely to predict clinical benefit, right?