A New Phase 2 Trial of Tominersen for Early Huntington Disease Designed

A new phase 2 trial is planned to evaluate tominersen (IONIS-HTTRx; Ionis Pharmaceuticals, Carlsbad, CA) to treat early-stage Huntington disease (HD). Although the phase 3 GENERATION HD1 trial of tominersen for HD was halted, post hoc analyses suggest tominersen may benefit younger adults with lower HD disease burden. Ionis' partner Roche is in early stages of designing the trial and more information will be available January 20, 2022.  Tominersen also reduced cerebrospinal fluid (CSF) levels of huntingtin (hTT) protein the GENERATION HD1 study.

Tominersen is an investigational antisense oligonucleotide designed to reduce the production of all forms of the huntingtin protein (HTT), including mHTT, the gain-of-function variant implicated in HD pathogenesis.

"These findings are promising and warrant a new study designed to test tominersen in this specific patient group. We are pleased that Roche has determined that there is a path to advance the tominersen development program," said C. Frank Bennett, PhD, Ionis' executive vice president, chief scientific officer and franchise leader for neurological programs. "This is an encouraging development for the HD community. We and Roche are grateful to the HD community's continued partnership, which has led to these important insights and a new scientific hypothesis."

The generation HD1 study was a double-blind placebo-controlled phase 3 clinical study for tominersen in participants with manifest HD over 25 months. Participants (n=791) were randomly assigned to receive 120 mg every 2 months or 120 mg every 4 months of tominersen or placebo administered as intrathecal injections.