A phase 2 trial of Quark Pharmaceuticals’ RNAi candidate QPI-1002 has met its primary endpoint. The p53 gene-targeting siRNA cut the rate of acute kidney injury (AKI) in patients following cardiac surgery, setting Quark up to advance the Novartis-partnered drug.
Investigators enrolled 341 adults at high risk of AKI in the trial and randomized them to receive either QPI-1002 or placebo after undergoing cardiac surgery. Participants received a single dose of the experimental drug and were monitored over the next five days for signs of AKI as defined by the RIFLE classification. Quark predicted QPI-1002 would stop the emergence of AKI by temporarily cutting expression of p53, a stress-response gene that can lead to cell death.
The Fremont, CA-based RNAi specialist now has data to back up its prediction. Incidence of AKI was significantly lower among patients who received QPI-1002, resulting in the trial hitting its primary endpoint. Quark said the data show QPI-1002 affects all its predefined patient subgroups, which include people with chronic kidney disease, diabetes and those who were at particularly high risk owing to the multiple cardiovascular surgical procedures they underwent.
Quark also said the trial met multiple secondary endpoints. The only secondary endpoint listed on ClinicalTrials.gov is the proportion of subjects who died, needed renal replacement therapy or had a 25% or more reduction in serum creatinine based estimated glomerular filtration after 90 days.
The biotech is yet to break out the numbers to show how much better than placebo QPI-1002 performed against any of the endpoints. Those numbers will shape the level of interest in the drug as it heads through development. But, when coupled to a comparable safety profile to placebo, whatever Quark has seen is positive enough for it to talk up advancing the candidate.
That represents a boost for Quark and QPI-1002, the progress of which has stuttered at points. A phase 2 trial of the drug missed its primary endpoint in 2014 after it cut the risk of delayed graft function by 15% compared to placebo. The threshold for success was 30%.
Novartis was due to decide whether to opt-in to the program within 90 days of getting a look at those data. But the Swiss Big Pharma ultimately amended the terms of the $680 million agreement to push back the decision date to the end of a phase 3 trial in delayed graft function. That clinical trial is currently enrolling patients with a view to delivering data in 2019. The primary endpoint is number of dialysis sessions, not incidence of delayed graft function.
Quark is now positioned to push deeper into the clinic in AKI, too. Surgeons currently lack effective ways to prevent AKI following cardiac procedures, resulting in about 30% of patients suffering such complications. AKI increases the risk of death during hospitalization. The risk is particularly acute for the small proportion of patients who require renal replacement therapy.