RG6496 / Roche, Ionis - LARVOL DELTA

POINT-HD: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease (clinicaltrials.gov) - P1 | N=3 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=40 ➔ 3

Enrollment change • Enrollment closed • First-in-human • CNS Disorders • Huntington's Disease • Movement Disorders

POINT-HD: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting | Trial completion date: May 2029 ➔ Dec 2026 | Trial primary completion date: Feb 2028 ➔ Dec 2026

Enrollment open • First-in-human • Trial completion date • Trial primary completion date • CNS Disorders • Huntington's Disease • Movement Disorders

POINT-HD: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • CNS Disorders • Huntington's Disease • Movement Disorders

Next Steps (Roche Press Release) - "Communications to Study Participants: Our immediate focus is supporting participants and sites regarding these announcements. Earlier this week, sites were notified so they could contact participants and discuss transition plans and support...Sharing Data & Learnings: Data will continue to be analysed and presented at future medical meetings. We are committed to sharing learnings with the research and family communities to advance the understanding of drug development for HD; Further Research: Roche’s Phase I/II study of investigational gene therapy RG6662 (formerly from Spark Therapeutics; study SPK-101, NCT06826612) is ongoing as planned. Additionally our interest in exploring multiple HD therapeutic approaches remains, and we will continue to follow promising science."

P1 data • P2 data • Trial status • CNS Disorders • Huntington's Disease

Update on Two Clinical Studies: GENERATION HD2 (tominersen) and POINT-HD (RG6496) (Roche Press Release) - "Consequently, we have made the difficult decision to discontinue both clinical development programmes based on: Phase II GENERATION HD2 top-line results...While the study met its safety and biomarker objectives, it did not meet its efficacy objective; Phase I POINT-HD (evaluating investigational drug RG6496) study discontinuation based on new data from a separate non-clinical (animal) study....Initial results of the primary analysis show...Biomarkers: Tominersen significantly lowered mutant huntingtin protein and Neurofilament Light Chain (NfL) (a protein linked to neuronal damage that is elevated in people with HD)...Efficacy: There was no meaningful impact on clinical efficacy for the study participants receiving tominersen, compared to those on placebo...While there is no safety concern for people to receive one dose, we have chosen to stop the POINT-HD study early, because we can no longer offer participants the possibility of long-term treatment."

Discontinued • P1 data • P2 data • Preclinical • Trial termination • CNS Disorders • Huntington's Disease

BP45378: A Study to Assess the Safety of RG6496 in Huntingtons Disease Gene Expansion Carriers with the Selected Genetic Variant (POINT-HD) (clinicaltrialsregister.eu) - P1 | N=25 | Not yet recruiting | Sponsor: F. Hoffmann-La Roche AG

New P1 trial • CNS Disorders • Huntington's Disease • Movement Disorders

POINT-HD: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Hoffmann-La Roche

New P1 trial • Huntington's Disease • Movement Disorders