The suspension of a small trial of the antisense Huntington’s project RG6042 (IONIS-HTT-Rx) being developed by Ionis and Roche knocked 3% of the former’s share price yesterday, despite Ionis’s protests that the halt did not affect any of the other ongoing RG6042 trials. The 20-patient Gen-Peak trial saw two cases of infection related to the use of intrathecal catheters to sample cerebrospinal fluid after drug administration. Roche is moving to shorten the CSF monitoring period – currently 48 hours – to avoid any more infections. Those seen so far were not related to the project, Ionis told analysts, saying that though RG6042 is dosed intrathecally this is done by injection. None of the other ongoing trials, including the pivotal Generation-HD1 and an open-label extension study intended to contribute to an accelerated approval application, use catheters, and remain unaffected by the halting of Gen-Peak. 15-month data from the extension study, released last month, suggest that RG6042 is engaging with mutant Huntingtin protein, and data on adverse events prompted Roche and Ionis to alter the dosing schedule in Generation-HD1 from every four or eight weeks to every eight or 16, since the latter regimen was safer.
|Trials of RG6042/IONIS-HTT-Rx|
|Gen-Peak: pharmacokinetic study (NCT04000594)||20||Dosing halted; data expected 2021|
|Placebo-controlled phase I/II trial (NCT02519036), to be used for accelerated approval||46||Post-hoc analysis reported April 2018|
|Open-label extension trial (NCT03342053), to be used for accelerated approval||46||Expected by end Q1 2020|
|Generation-HD1: pivotal, placebo-controlled phase III trial (NCT03761849)||909||Expected H2 2022|