Guard argues new data render primary endpoint miss 'irrelevant,' tripling share price

Guard Therapeutics is mounting a bullish bounce back from the failure of its phase 2 kidney injury clinical trial. A primary endpoint failure brought the study to an early end, but the Swedish biotech branded that setback “irrelevant” Tuesday, arguing that longer-term efficacy assessments show its asset has a future. 

The phase 2 study was primarily designed to show whether RMC-035, a recombinant variant of a protein linked to organ protection, is better than placebo at preventing acute kidney injury (AKI) in the 72 hours after heart surgery. An interim look at the primary endpoint data suggested RMC-035 is not better than placebo on that measure, but Guard continued to track longer-term outcomes in the 177 participants. 

Now, Guard has shared the longer-term secondary endpoint data. The company powered the trial so all p-values below 0.1 are statistically significant and came in below that bar on two of its 90-day secondary endpoints. 

The difference in eGFR change, a measure of kidney function, from baseline on Day 90 favored RMC-035 over placebo, yielding a p-value of 0.06. Guard also tied RMC-035 to a reduction in major adverse kidney events through Day 90, with the difference between the rate in the treatment arm, 6.7%, and placebo group, 15.9%, resulting in a p-value of 0.047.

A potential problem is that the primary endpoint failed comprehensively. The rate of AKI in the RMC-035 group, 50.6%, was higher than in the placebo group, 39.8%. Guard attributed the result, and potentially the primary endpoint flop, to a drug-induced increase in serum creatinine in recipients of RMC-035 and argued against focusing on the AKI data. 

“It is important to note that AKI merely serves as a short-term prognostic indicator of clinically relevant outcomes, including long-term kidney function and major adverse kidney events. The actual efficacy of RMC-035 assessed by these hard clinical outcomes is far above expectations and makes the chosen primary endpoint, AKI, irrelevant in this context,” Guard CEO Tobias Agervald said in a statement.

The message resonated with some investors. Guard’s share price tripled in the wake of the update, rising from 0.16 Swedish kronor ($0.01) to 0.48 Swedish kronor, but still remains below the price it commanded before news of the primary endpoint failure emerged in April.