Angion’s kidney transplant dream dies
The group will have to pivot to a heart surgery setting, but the omens here are not good. Meanwhile, Vifor’s run of bad luck continues.
Angion Biomedica’s hepatocyte growth factor mimetic ANG-3777 has failed to improve kidney function in transplant recipients. Can it treat acute kidney injury in people who have undergone a heart and lung bypass?
The group’s investors are sceptical on this question judging by the 54% downturn in Angion’s shares so far today. Vifor Pharma, with whom the asset is partnered, is only down 4%, but following the failure of Akebia’s anaemia project vadadustat, to which Vifor also has rights, this is a loss it can ill afford.
The pivotal US-based phase 3 trial was intended to show that ANG-3777 could treat delayed graft function in kidney transplant recipients. The 253 patients in the trial had been determined to be at risk for delayed graft function as they had had low urine output for more than eight consecutive hours post-procedure.
But the agent made little difference to renal function as measured by estimated glomerular filtration rate at one year. Patients given ANG-3777 showed a slight but not statistically significant improvement over the placebo recipients. A per-protocol analysis, counting only those subjects who completed the trial, found a stronger effect but also missed significance by a whisker.
|Phase 3 data on Angion/Vifor's ANG-3777|
|12mth eGFR in total trial population (mL/min/1.73m2)||53.3||50.4||2.9||0.33|
|12mth eGFR in only those who completed the trial (mL/min/1.73m2)||57.1||52.2||4.9||0.06|
|Source: company release.|
Angion described the long-acting molecule’s performance on the trial’s secondary endpoints as “inconsistent”. Safety, at least, was clean.
The miss being pretty incontrovertible, Angion and its partner Vifor have done the decent thing and canned ANG-3777’s development in this indication.
And with that their efforts turn to ANG-3777’s other indication, acute kidney injury associated with cardiac surgery (CSA-AKI). Top-line data from a “signal-finding” phase 2 study in cardiopulmonary bypass patients are expected this year.
The primary endpoint is a measure of serum creatinine increase, and an important secondary is major adverse kidney events at 90 days (Make 90), which has previously been agreed by the FDA as a suitable primary endpoint for a registrational trial in this indication. Make 90 events are death, initiation of renal replacement therapy or a decline of more than 25% in eGFR.
Stifel analysts write that the reperfusion injury in CSA-AKI is similar to delayed graft function but potentially less severe and more consistent. They suggest that the different trial design – the cardiac trial has an additional day of dosing and a 90-day endpoint – could improve its chances of succeeding.
In search of an encouraging example, the analysts point to Quark Pharma’s small interfering RNA QPI-1002. This also failed in delayed graft function but showed activity in CSA-AKI, in a 341-patient phase 2 study, yielding a 26% relative risk reduction in the proportion of subjects with AKI at day five versus placebo. It failed, however, on Make 90.
This did not stop Quark using Make 90 as the primary endpoint for the phase 3 trial of QPI-1002. According to its record on clinicaltrials.gov, the pivotal, too, failed this test and follow-up has been terminated. It is unclear whether the programme is still active.
The Stifel analysts put ANG-3777’s odds of success in CSA-AKI at a mere 45%, and forecast peak US sales of $209m in 2032.
As for Angion, its third-quarter cash balance is believed to be around $100m, which could see it through the CSA-AKI trial and perhaps beyond. But, since it floated in February, Angion's stock has lost nearly three quarters of its value.