On October 8, Roche announced that its anti-amyloid beta antibody, gantenerumab, had been awarded breakthrough therapy designation (BTD) from the FDA for the treatment of Alzheimer’s disease (AD). The BTD was granted based on data from the ongoing Phase III SCarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) open-label extension (OLE) trials, which showed that gantenerumab significantly reduced brain amyloid plaque.

The AD market is currently dominated by symptomatic treatments. However, there are a number of promising disease-modifying therapies (DMT) in late-stage development. These therapies are vying to become the next breakthrough therapy after Biogen’s Aduhelm (aducanumab) became the first DMT to reach the AD market in early June 2021. The BTD for gantenerumab follows the FDA granting BTDs in late June for Eisai and Biogen’s lecanemab (BAN2401) and Eli Lilly’s donanemab, both of which also aim to reduce the formation of amyloid plaques in the brain of AD patients.

Like Aduhelm, lecanemab and donanemab are intravenously administered monoclonal antibodies (mAbs), whereas gantenerumab would become the first subcutaneously administered mAb for AD. This alternative route of administration provides a point of difference, and a potential competitive edge for gantenerumab, as subcutaneous administration could allow for at-home administration.

However, there are still challenges for gantenerumab if it is to succeed as an AD treatment. In general, with amyloid-base therapies, there are concerns regarding the development of amyloid-related imaging abnormalities (ARIAs), and although gantenerumab has been reported to be generally safe and well-tolerated, ARIAs were observed in some participants in early Phase I trials. Therefore, long-term safety results from ongoing Phase III trials will be important for gantenerumab’s success. Additionally, previous clinical trial failures, including the DIAN-TU trial (NCT01760005) and the blinded part of the SCarlet RoAD trial, which failed to show significant results, have cast some doubt over the efficacy of gantenerumab. However, this does not mean that gantenerumab will fail to reach the market. Biogen and Eisai initially announced that they would be discontinuing Aduhelm for futility, before reanalyzing data from the pivotal Phase III trials (Engage [NCT02477800] and Emerge [NCT02484547]) used to support its approval. Despite the controversy surrounding its approval, Aduhelm has a huge advantage over the pipeline products as the first DMT to enter the market. GlobalData forecasts that Aduhelm will generate close to $3bn across the 7MM and China by 2030.

In addition to the SCarlet RoAD and Marguerite RoAD OLE studies, there are also two ongoing global, parallel, placebo-controlled, randomized Phase III trials for gantenerumab, GRADUATE 1 and 2 (NCT03443973 and NCT03444870), which are expected to finish in H2 2022. GlobalData forecasts that gantenerumab will launch in the US in 2024 and will generate global sales of around $2.2B across the 7MM and China by 2030. Gantenerumab’s competitors, lecanemab and donanemab, are both expected to launch in the US in 2024 and generate global sales of close to $2.2bn and $3bn, respectively, by 2026.