I think it’s important to remember that a lot of CKD/DKD patients can’t tolerate SGLT2 (side effects) and is contraindicated in patients with a history of DKA.
This has been a problem in COVID-19 infection & I read a recent article advising to suspend these drugs in hospitalised patients, although AZ are trialling Dapa in COVID19.
So for these patients, they need to be treated with an alternative, which at the moment is ARB or ACEi plus glycaemic control for diabetes & DMX-200 a candidate for this scenario as well.
I think the idea of a combo with SGLT2 is fantastic & potentially a clinically significant further reduction in UACR could give a very significant market advantage in SGLT2i market (from memory $USD 6 billion and growing).
In regards to Orphan status for FSGS, you are correct, it can’t be granted if you are pursuing a market application for a more common drug. However, it is anticipated FSGS will be first cab off the rank, the benefit of Orphan Status will be in R&D, single smaller Ph3, priority approval and financial benefit in drug development. Of course down the track when DMX-200 is marketed for DKD, then the FSGS patients will not be paying orphan drug prices.
This is what Big Pharma do (whether that is ethical or not) & DKD will take longer with much larger trials in Ph3.
In the case of Dimerix, we had Orphan status prior to the discovery in Ph2A that the diabetics on the trial had an excellent response, which prompted Ph2b in DKD.
The number of patients with FSGS are growing in the USA & 2.7 per 100000 new diagnoses estimated per year. With COVID now it could be higher with viral induced FSGS, we already know HIV can cause it & it’s higher risk in patients of African descent who carry APOL1 gene. Insurance companies will pay for orphan status drugs when there is no alternative & the cost of treating ESRD is much higher. Transplantation is often rejected in FSGS, so dialysis the only option once it gets to that stage.
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