Abstract Details

Throughout the gantenerumab clinical development program, subcutaneous administration was continuously evaluated and optimized. A summary of findings supporting the value and feasibility of subcutaneous administration is presented.

Gantenerumab is a subcutaneously-administered fully human anti-amyloid monoclonal antibody with highest affinity for aggregated amyloid-beta. Subcutaneous administration allows a flexible administration setting, with the potential to accommodate lifestyle differences and treatment access across different healthcare systems.

A summary of evidence from the gantenerumab clinical development program is reported including: a) a randomized, placebo-controlled crossover study in healthy participants to evaluate injection pain following subcutaneous administration of gantenerumab versus placebo (NCT02882009); b) assessment of feasibility of care partner-assisted at-home administration in a Phase II study in participants with early AD (NCT04592341); c) plasma concentrations and pharmacokinetic characteristics from a population pharmacokinetic model analysis.

Subcutaneous gantenerumab was locally well tolerated with predominantly mild, reversible, and self-limited injection-site reactions. Minimal to slight pain was reported (verbal-rating scale) after needle insertion with minor differences recorded for gantenerumab versus placebo. Visual analogue scale (VAS; from 0 [no pain] to 100 [worst pain possible]) least square means were 15.006 vs 9.526, respectively (mean difference 5.48; 95% CI –1.971 to 12.931). Pain was reported directly after injection and subsided within 5 minutes (VAS < 5 mm). Pharmacokinetics of subcutaneous gantenerumab was comparable across clinical studies.

The Phase II study included a home-administration questionnaire to assess confidence of care partners as drug administrators, ease of use, and convenience.

Subcutaneous gantenerumab administration was well tolerated locally, providing reliable drug exposure with minimal pain experience. These findings provide a greater understanding of subcutaneous administration with an anti-amyloid therapy in Alzheimer’s disease and may further enhance the value of this route of administration.