dirk haussecker, page-7

Time is running out for Benitec

Benitec announced today that almost 1 ½ years after filing an IND for its DNA-directed RNAi HCV candidate, it has now obtained liver biopsy data from first 3 of the 4 patients dosed so far. Needless to say, the analysis was a resounding success confirming that the right AAV vector coding for the shRNAs against HCV was administered to the trial subjects.

Given that no details were provided on the methods, I assume that the evidence is based on PCR analysis which pretty much picks up almost any activity.

TT-034 also shined on safety with ‘no treatment-related serious adverse effects (SAEs) in any of the four patients dosed’.

To wit, the motivation behind the gene therapy ddRNAi HCV trial is to provide a one-shot cure from HCV infection. The company, however, said that ‘the amount of shRNA produced will not result in reduction of hepatitis C viral load’.

So while this statement almost makes it sound like they did not look for antiviral efficacy, but that there might well have been, we can safely assume that they did (standard blood test to look for HCV; plus RNA analysis from biopsies) and failed to see such.

It is also curious that no results from PCR-based target mRNA cleavage assays were disclosed which, while still PCR, requires a certain amount of RNAi robustness to detect with confidence and would have been used to further tout trial success.

At this point, Benitec has almost completed the first 2 of 5 planned dose cohorts. According to my notes, the top dose is about 25x higher than dose group 2. To get from no change in viral titer to undetectable while increasing dose by 25x seems quite optimistic to me. And even if this highly unlikely scenario materialized, at this pace, it will be sometime in 2023-4 when it would even be considered for approval.

So please, Benitec, if you cannot see a knockdown at the next higher dose cohort, give it a rest.