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skyblue008 发表于 2020-9-15 15:29 
你说的没错。其实不是纠结primary endpoint，而是这是临床试验最核心的东西。然后即使抛开这个，它们的结 ...
下面是HC 一个大神发表的 DXB和另外一个FDA已经批准的药物对比。当然这个大神已经被骂的不敢见人了。
药物研发怎么可能一帆风顺，各种稀奇古怪的问题多了去了。只要这个公司能够提出科学依据，妥善解决遇到的问题就是了。
FDA批准的药物也不会是十全十美。看看下面的大神的说明就知道了。
至于DXB 最终会怎么样，只有GOD knows。
The Legacy effect will be interesting - patients were thier own placebo, so they should be able to work this out, if this is the case from patients’ baseline ACR in the first treatment group.
So to put things into perspective, it might be a good idea to reflect on Canafliglozin results from their CREDENCE trial, which granted it the only drug to be approved for the prevention of decline of renal function in the last 20 years, both by the FDA & EMA.
There are significant side effects with this class of drugs, which have included deaths & side effects are multiple, tables in the link below.
It’s important to note that the primary endpoints in this trial were for e/GFR, what we are looking at is a % reduction in albuminuria. Professor Hiddo Heerspink (Chair of Dimerix Medical Advisory Board) was also a co-author on this trial paper.
The CREEDENCE trial enrolled ~4400patients, which 1201 dropped out from the trial before completion, which had a median timeframe for follow up of 2.6 years (0.02-4.53 years).
The ACR at baseline was >300-5000mg/g, with a median baseline of 913.5mg/g. The patients were also on ARBs, so not mono therapy. Results were a geometric mean lowering of ACR of 31%. If you look at Figure 3 in results section, the decline in ACR was over 6 months, before stabilising. DMX-200 patients were on randomised treatment for 12 weeks.
https://www.nejm.org/doi/full/10.1056/nejmoa1811744
If you take into consideration that a mean 31% lowering of ACR over such a large cohort of patients, the 6 month period of downtrend of albuminuria on canafliglozin before stabilisation, and some patients with very high albuminuria levels on this trial with a mean of 913.5mg (up to 5000mg/g), our numbers are not looking so bad after all with 25% of patients having a reduction of >30% and 64% having a reduction over SOC, now that we know the patients with higher levels of proteinuria were responding to treatment.
Also taking into consideration that anything above 15% reduction on top of SOC is clinically significant, particularly in an unmet clinical need (for many patients who are contraindicated for, or can’t tolerate SGLT2s).
I think the reaction of the market was panic stations yesterday, but I agree the ANN was difficult to understand & without reading it all, could look like a failure, even though the heading stated positive results. I haven’t sold any shares & still well above my average & glad I didn’t get time to look yesterday because it would have been very upsetting.
Waiting on the post hoc for the responder group >500mg/g baseline albuminuria, and breakdown of trial participants, just like we did in Ph2A. We know DMX-200 is efficacious above 500mg/g & not below this treatment point, so it will be interesting to see the breakdown of this group in correlation to baseline ACR.
Certainly not giving up hope on DMX-200 in this indication for DKD.
If I remember correctly there was a bit of concern over FSGS results as well until it was pointed out that we had in fact pipped Retrophin’s primary endpoint of 40% reduction in ACR (including the ARB factor with Spartensan). Chemocentryx fell off the radar with a Ph2 failure in FSGS & DKD has never been developed with Vifor after their Ph2, probably due to breach of DXB patents. Retrophin are not conducting trials in DKD, from what I can see on their website.
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楼主:Victor2020
发表于 2020-9-15 06:11
