Dimerix (ASX: DXB) Discussion Thread, page-153

Hi @butcherano,

Of course, no probs I knew your username was familiar. All good & I can see you have spent a lot of time DYOR & it’s not like “gimme all you got”…Kidney Disease is a lot to get your head around & DXB history! Some very interesting questions, so I think that the below will help you a lot! I agree with you a not a lot on eGFR but below will help! Other biomarkers more helpful in the shorter term (for FSGS).

A lot has changed in the kidney disease RCT space since we have completed Ph2 trials - a lot of research going on there on trial designs. This may help to answer all your questions mate, & this is what is informing the FDA & EMA on surrogate endpoints. This is particularly about Proteinuria & eGFR slope.

https://www.siditalia.it/images/Levey.pdf

This study cites a major meta-analysis on CKD trials & a simulation study. You can access those papers via the reference list, so I won’t repost. It’s also a very lengthy paper: Cheat tip, the Blue text boxes & summaries will most likely give all you need.

There is more out now also & international guiding bodies like KDIGO & NKF in the USA involved on the work to standardise CKD trials & surrogate endpoints.

Professor Heedo Heerspink was instrumental in DXB’s Ph3 ACTION trial design & we are very fortunate to have such an experienced CKD MAB member on our side, & when you start looking at International papers, he’s very busy, not just on BP trials, but on International Advisory Boards & Academia in the CKD space.

You would have seen some of the earlier work as well going over old posts. You would have seen our trial timeline changed very early on. Questions Answered!

And it does get a bit complicated, because kidney disease trials are not apples & apples. I agree with you that there is not a lot on eGFR data from earlier trials, however once you read the above paper, it becomes a little clearer why…not long enough to be discussing & as I said earlier, there has been some muddiness with clinical trials & measurement of eGFR too early in chronic CKDs, either chronic slope or total slope, what to use?

It’s not like you get a patient into ED in acute renal failure because of severe dehydration or an acute infection & their eGFR improves or normalises the next day after pumping through a few bags of IV fluids +/- IV Abs. It’s the slope, but also a very useful biomarker for acute kidney disease.

We know with FSGS, it can be about 5 years to dialysis without intervention or shorter, patients are individual how they will progress. It’s an unmet clinical need & some of these patients are little kids. The FDA have approved for Paediatric patients to go onto the trial & is the norm, will be 12-18yos initially. Then that age range may drop down with ongoing safety & efficacy data. Some little ones are diagnosed as toddlers. Kidney transplants often fail in these patients as well, so that really sucks!

There is a lot in these articles on treatment affect, that is Evident by 6 months. Something that is now well known is that with eGFR & SGLT2i class of drugs (DKD,CKD,CVD), the eGFR actually worsens in the early stages of treatment before an improvement is seen!

We are not expecting that with DMX-200, but having said that, we are looking at a chronic kidney disease with FSGS, and even following Ph2b in DKD, the consensus was that a longer trial was needed (remembering it was a crossover design as well & far shorter in the treatment period). One of the positive outcomes of these data analyses is shorter timelines for monitoring & our patients can go on OLE (Open Label Extension after week 104 I believe). That’s ethical & I’m happy about that.

I think in regards to the study being blinded & a Ph3 RCT, those questions have been answered already about what will be released in March 2024 after the ICMB review. So I’m not worried, I just thought that people here would understand this about eGFR in particular. It’s still going to be done in all blood tests, it’s just not an Endpoint until week 104 Interim 2.

When you read the article, you will see about Proteinuria & eGFR marrying up well as surrogate endpoints.