nivegacetor (RG6289) / Roche - LARVOL DELTA

A Study of Donanemab, RG6289, or the Combination of Donanemab and RG6289 in Presenilin 1 (PSEN1) E280A Mutation Carriers for the Treatment of Autosomal-Dominant Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=240 | Not yet recruiting | Sponsor: Banner Health

New P2/3 trial • Alzheimer's Disease • CNS Disorders

A Study Investigating [14C]-Labeled RO7269162 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Hoffmann-La Roche | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Safety and Biomarker Effects of RO7269162 in Participants at Risk for or at the Prodromal Stage of Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2027 ➔ Oct 2026 | Trial primary completion date: May 2027 ➔ Oct 2026

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

A Study Investigating [14C]-Labeled RO7269162 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open

Drug Development. (PubMed, Alzheimers Dement) - "Our novel orally available GSM RG6289 has completed the Phase 1 study in healthy young and elderly volunteers...The Phase 2 study in individuals with AD is expected to start this year. Challenges of developing in clinic a new mechanism of action, as well as considerations regarding how to best position this molecule for AD will be discussed in this presentation."

Journal • Inflammation • APP • Aβ42

Developing Topics. (PubMed, Alzheimers Dement) - "In humans, RG6289 produced a dose-dependent shift in the production of longer (Aβ40 and Aβ42) and shorter (Aβ37 and Aβ38) Aβ monomers in CSF. The results from this study support the further clinical development of RG6289 for the treatment of AD with the goal to reduce production of Aβ42, increase the levels of smaller Aβ species and slow-down or halt Aβ aggregation and accumulation as an approach to altering AD progression."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Aβ42

A Study Investigating [14C]-Labeled RO7269162 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1 trial

Pharmacodynamic effect of a new γ-secretase modulator, RG6289, on CSF amyloid-β peptides in a randomized Phase I study (AAIC 2024) - "In humans, RG6289 produced a dose-dependent shift in the production of longer (Aβ40 and Aβ42) and shorter (Aβ37 and Aβ38) Aβ monomers in CSF. The results from this study support the further clinical development of RG6289 for the treatment of AD with the goal to reduce production of Aβ42, increase the levels of smaller Aβ species and slow-down or halt Aβ aggregation and accumulation as an approach to altering AD progression."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Aβ42

Gamma-secretase modulation: from bench to clinic (AAIC 2024) - "Our novel orally available GSM RG6289 has completed the Phase 1 study in healthy young and elderly volunteers...The Phase 2 study in individuals with AD is expected to start this year. Challenges of developing in clinic a new mechanism of action, as well as considerations regarding how to best position this molecule for AD will be discussed in this presentation."

Inflammation • APP • Aβ42

A PHASE IIA STUDY INVESTIGATING A GAMMA-SECRETASE MODULATOR IN INDIVIDUALS AT RISK FOR OR AT THE PRODROMAL STAGE OF ALZHEIMER'S DISEASE (ADPD 2024) - "GABriella is the first clinical trial exploring the effect of a brain-penetrant, potent and selective GSM on amyloid positive individuals, who are cognitively unimpaired or have MCI due to AD."

Clinical • P2a data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Aβ42

RG6289, a new γ-secretase modulator for the treatment of Alzheimer's disease: Results from a phase I healthy volunteer study (CTAD 2023) - "RG6289 showed a favorable safety and tolerability profile across all single and multiple doses in young and elderly healthy volunteers in this study. Proof of mechanism was demonstrated based on the observed enzyme modulation increasing levels of Aβ38 and Aβ37, whilst reducing Aβ42 and Aβ40. Results from this study support the further clinical development of RG6289 for the treatment of AD."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • APP • Aβ42

RG6289, a new γ-secretase modulator for the treatment of Alzheimer's disease: Dose selection for a phase II trial based on population PK/PD modeling (CTAD 2023) - "Based on the final population PK/PD model, food did not have any relevant effect on the PD of RG6289. Age effects on PK were taken into account when selecting the final doses for the upcoming Phase IIa study. The three selected doses are covering a broad range of Aβ42 lowering expected to be therapeutically relevant in the very early stages of AD."

Clinical • P2 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Aβ42