The neurodegeneration program lead at Genentech offered his perspective on the phase 3 SKYLINE trial and the historical data on gantenerumab ahead of this new clinical assessment.
Greg Rippon, MD, MS
Last week, Roche, announced that it was initiating a new trial of its investigational antiamyloid antibody, gantenerumab, a phase 3 clinical trial in those with early signs of Alzheimer disease (AD) dubbed SKYLINE (NCT05256134).1 The trial design is expected to be presented on March 18, 2022, at the 2022 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD), in Barcelona, Spain.
SKYLINE’s initiation follows another pair of ongoing phase 3 trials of the therapy, GRADUATE 1 (NCT03444870) and GRADUATE 2 (NCT03443973), which are expected to read out data in Q4 2022. Gantenerumab was also previously granted a breakthrough therapy designation in fall 2021 by the FDA. The therapy is an IgG1 antibody that binds to ß-amyloid aggregates to remove amyloid plaques, delivered subcutaneously.
To find out more about the SKYLINE trial and gantenerumab to this point, NeurologyLive® inquired with Gregory A. Rippon, MD, MS, neurodegeneration program lead, Genentech (a member of the Roche Group), who offered his perspective on the trial’s goals and design and context on what is known to this point about Roche’s investigational therapy.
Gregory A. Rippon, MD, MS: SKYLINE aims to evaluate the potential of gantenerumab to slow the progression of Alzheimer in people with the earliest biological signs of the disease.
The trial has been uniquely designed to address some of the perceived barriers to participation in clinical research for the clinically asymptomatic Alzheimer population. This includes optional blood-based biomarker (BBBM) prescreening for participants and providing the choice to participants of dosing every 1 or every 2 weeks, with the flexibility of administration at home following a titration period. Also, for participants who are randomized to placebo and progress to mild cognitive impairment or dementia due to Alzheimer within the 4-year study period, we will offer gantenerumab investigational treatment, unless the ongoing phase 3 studies of gantenerumab in early AD (GRADUATE 1 and 2) do not demonstrate efficacy.
We have been studying and developing gantenerumab for 2 decades. Over the years, we have faced setbacks in this program and in Alzheimer disease therapy development more broadly, but we have gleaned significant scientific insights on ß-amyloid lowering—as well as on biomarkers, dosing approaches and clinical trial design—that have contributed to the body of science and understanding of AD.
Notably, we have built on our experience and these learnings from our clinical development program to inform the design of our ongoing phase 3 GRADUATE clinical trials, for which data is expected in the fourth quarter of 2022. Regardless of the outcome, we expect this to be one of the most important datasets to emerge from the AD field. And if positive, the findings will enable us to seek full regulatory approval for gantenerumab from the FDA.
Screening of potential participants was initiated in late January 2022. The study will enroll 1200 participants, who will be randomized to receive gantenerumab or placebo for 4 years.
Transcript edited for clarity.