Roche Suspends Phase 1 Trial Testing Tominersen (RG6042) for Huntington’s

A Phase 1 clinical trial testing Roche’s investigational therapy tominersen for Huntington’s disease has been placed on hold after two cases of infection were found during the study.

The infections were linked to the device used to take samples of patients’ cerebrospinal fluid (CSF, the liquid surrounding the brain and spinal cord), and the suspension does not seem related to the investigational compound itself (previously known as IONIS-HTTRx and RG6042). No other trials of tominersen will be impacted.

Huntington’s is caused by a mutation in the huntingtin (HTT) gene which leads to the production of abnormal RNA molecules — the genetic blueprints for making protein — and, ultimately, an abnormal HTT protein.

Tominersen was first developed by Ionis Pharmaceuticals and later acquired by Roche. It is an antisense oligonucleotide, or antisense therapy, designed to target and destroy all forms of mutated HTT protein. The candidate has the potential to treat all Huntington’s patients, regardless of their individual HTT mutation.

The open-label Phase 1 trial (NCT04000594) is investigating the pharmacokinetics and pharmacodynamics of tominersen when injected directly into the spinal canal (intrathecal administration). Of note, pharmacokinetics refers essentially to how the body affects a medicine while pharmacodynamics assesses the interactions between the body and the compound.

Additionally, the trial will assess the therapy’s safety and tolerability following intrathecal administration.

The trial in planning to enroll 20 patients and divide them into three groups to receive three different doses of tominersen, administered in two intrathecal injections of the same dose level 28 days apart.

Patients’ blood and CSF samples are collected to measure the trial’s parameters over time (up to six months after last tominersen administration). For CSF collection, an intrathecal catheter is used. Infections related to this procedure were the cause of the trial’s suspension.

The suspension will likely allow Roche to modify the protocol to reduce the length of time intrathecal catheters are placed, or to find a different solution for collecting the CSF samples, according to a news story.

Other trials testing tominersen, including the ongoing Phase 3 GENERATION HD1 study (NCT03761849) assessing the potential of tominersen to delay disease progression, are expected to continue as planned.