Yesterday’s positive phase II trial result for Reata’s bardoxolone methyl – the latest of several – should give Abbvie pause for thought. The big pharma had pumped $1bn into Reata to license bardoxolone for a broad use that failed, but has no involvement in the rare kidney disease indications now being pursued.
Since that 2012 setback, when bardoxolone bombed in a phase III trial in chronic kidney disease, Reata has gone from strength to strength. Unless Abbvie chooses to pay it yet more cash Reata, now boasting a $2.6bn valuation, looks set to commercialise bardoxolone itself for five types of kidney disease.
The disease where bardoxolone read out positively yesterday – focal segmental glomerulosclerosis – is one of four studied in the phase II Phoenix trial. The fact that Reata’s stock barely moved shows how predictable this outcome was, coming as it did on the heels of success in Phoenix’s three other cohorts.
Those three cohorts are IgA nephropathy, type 1 diabetic chronic kidney disease and autosomal-dominant polycystic kidney disease; the last of these is the only one in which Reata has revealed a path forward, planning to start a pivotal study, Falcon, in mid-2019.
But it is a fifth potential use that is the most advanced. Chronic kidney disease caused by Alport syndrome gave bardoxolone its first major win, last July (Reata gets full marks for perseverance and biz dev nous, July 24, 2018).
It is this indication that represents Reata’s most important catalyst, readout of the phase III portion of the Cardinal trial, due in the second half of this year.
|Bardoxolone's current potential uses|
|Cardinal phase II||CKD caused by Alport syndrome||25||Positive|
|Phoenix cohort 1||Autosomal-dominant polycystic kidney disease||31||Positive|
|Phoenix cohort 2||IgA nephropathy||26||Positive|
|Phoenix cohort 3||Type 1 diabetic chronic kidney disease||28||Positive|
|Phoenix cohort 4||Focal segmental glomerulosclerosis||18||Positive|
|Cardinal phase III||CKD caused by Alport syndrome||187||Due H2 2019|
|Falcon phase III||Autosomal-dominant polycystic kidney disease||~300||Trial starts mid-2019|
In the latest Phoenix success, meanwhile, bardoxolone demonstrated an increase in estimated glomerular filtration rate from baseline after 12 weeks, and this also compared favourably with 17 of the 18 patients’ historical data, which showed a worsening filtration rate before they received the drug.
Thus the Phoenix study has been deemed a success overall, showing a filtration rate improvement from baseline in the total 103 enrollees across all cohorts, with a similar backing from historical data, which were collected from 91 of the subjects.
Perhaps most importantly, Reata said no treatment-related serious adverse events were reported, and 89% of the Phoenix subjects completed 12 weeks’ treatment. Investors will no doubt recall the project’s 2012 blow-up as having been the result of a safety imbalance between the active and placebo arms in the broad chronic kidney disease study population.
According to Reata’s deal with Abbvie, which was never rescinded, the big pharma company is not participating in bardoxolone’s development for rare kidney diseases, but it has the right to opt in at any time in return for an undisclosed fee.
Whether it does so will depend as much on bardoxlone’s implied valuation as on Abbvie’s appetite for rare diseases.