Hi All,
I agree, while we did not meet the primary endpoint & patients with almost 1/2 proteinuria levels as on the previous trial 2A were included in Ph2b, the results showed benefit in the subgroup >500mg/g albuminuria baseline.
While it’s disappointing for us all (the SP tank) I think it needed to be done, (the lower threshold of proteinuria <500mg/g).
From the ANN “Topline data of all patients on the study suggests that 25% demonstrated a >30% reduction in albuminuria on treatment with DMX-200 vs placebo. 64% had a reduction in albuminuria, 56% had a clinically significant >25% reduction above SOC.”
And yes, I found the way the ANN was written a bit bamboozling especially only having a couple of minutes to read it, the good stuff should have been at the top in regards to the sub analysis, but I guess it had to be written in such a way that reflected the statistical analysis for the primary endpoint, to satisfy the ASX.
Its a bit like history repeating itself, I think we need to wait for the post-hoc analysis & unfortunately I couldn’t get to listen in on the investor call yesterday, but thanks to all who posted some key points.
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/nejmoa1811744If 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.
GLTAH, see what today brings.
(20min delay)