Ann: Quarterly Appendix 4C and Activities Report, page-210

Hi Dyeman & All,

Yes normally you would require a larger cohort to establish safety & efficacy, but rare disease status/orphan status is not classed in the “normal” trial design range. These patients are harder to recruit due to rare disease (and we in fact saw this, opening up a new trial site in WA towards the end of recruitment).

(N=10) is perfectly fine for a rare disease trial:


Not all patients reached the high bar of 50% above SOC (Ibersartan), but the average was 36% above SOC. I think it’s also important to note the responders in light blue in the figure above, their diagnosis was undisclosed as “other” in an a trial of n=27, the subgroup analysis is listed below:

https://www.asx.com.au/asxpdf/20171102/pdf/43nx4g3z7l9zgv.pdf

Iga Nephropathy were excluded from the trial inspite of being responders, when it was first planned to include them, Why?

(n=2) did not complete the trial for reasons otherwise. 1 didn’t complete data requirements. So that equates to 23. It’s wise what the company did when (n=40) for DKD for meaningful statistical analysis & in fact recruited (n=45). It could have been a nightmare especially in the current climate of COVID. Same goes for FSGS.

I think it’s also pretty wise to take on board that all on current 2a & 2b Trials for FSGS & DKD were required to be on a stable dose of 300mg of Irbesartan, whereas the prior trial of Ph2A of all-comers for CKD were not, a stable dose of 75mg & above, so 150mg & 300mg. This could make a difference to efficacy, so it’s really good they randomised their current trials in such a way, as the drugs work in synergy.

https://www.asx.com.au/asxpdf/20171102/pdf/43nx5vslh0d9r7.pdf

Good luck all & HAGWE.