Roche ducks out of AC Immune Alzheimer's antibody alliance

After almost 18 years of collaboration, Roche’s Genentech unit has ended a collaboration with AC Immune on Alzheimer’s disease therapies, handing back rights to two antibody-based drugs.

The end of the alliance doesn’t come as a huge surprise, given that both antibodies – anti-amyloid drug crenezumab and anti-tau candidate semorinemab – have both chalked up failed clinical trials as treatment for early-stage Alzheimer’s in the last few years.

Lausanne, Switzerland-based AC Immune said it would take a look at data from both programmes before deciding on the future of the drugs, including open-label extension results from the LAURIET trial of semorinemab, which showed an improvement in cognitive decline, but no effect on functional decline, in mild-to-moderate Alzheimer’s patients at its main readout in 2021.

Genentech licensed rights to crenezumab in 2006, and in 2012 broadened the partnership to include semorinemab, gaining drugs that target the two main histological hallmarks of Alzheimer’s disease – amyloid plaques and tau tangles. The two deals had a combined value of more than $700 million.

Crenezumab failed a pair of phase 3 studies in people with prodromal to mild sporadic Alzheimer’s in 2019, and Genentech continued to test the drug’s promise as a treatment for a rare, inherited form of the disease in the phase 2 API-ADAD trial, which was also a bust.

In 2022, AC Immune said it had found some positive efficacy signals after sifting through the API-ADAD data. However, that was clearly not enough to keep Genentech interested in the programme, particularly with one approved anti-amyloid drug on the market – Eisai/Biogen’s Leqembi (lecanemab) – and another from Eli Lilly (donanemab) under regulatory review.

Semorinemab, meanwhile, missed the mark in the phase 2 TAURIEL study in 2020, and the glimmers of efficacy in LAURIET were not enough to sway Genentech, which has had a bad run of luck with Alzheimer’s candidates in the last few years. In 2022, another of its amyloid-targeting drugs, gantenerumab, failed two phase 3 trials and was also abandoned.

AC Immune’s share price barely quivered upon the announcement, suggesting it was anticipated by investors, and the company said in a statement that it was focused on progressing its three active immunotherapy candidates through clinical testing.

That includes its wholly-owned amyloid vaccine ACI-24.060 and tau vaccine ACI-35.030, partnered with Johnson & Johnson, which are both in phase 2 studies that chief executive Dr Andrea Pfeifer said are “potentially registrational”.

It also has a Parkinson’s disease candidate, ACI-7104.056, which targets alpha-synuclein and is also in mid-stage testing.

Pfeifer said that regaining rights to crenezumab and semorinemab raises the prospect of combining them with its active immunotherapies. She also noted that the company remains well-financed after a $50 million fundraising round last month and a recent milestone payment from J&J that will extend its cash runway into 2026.

Roche remains committed to Alzheimer’s despite the return of the two antibodies, though its lead candidate now is bepranemab, an anti-tau candidate licensed from UCB that is in phase 2 testing.

Following directly after are trontinemab, a tweaked version of gantenerumab designed to improve its ability to penetrate the central nervous system, and a new-generation small-molecule gamma-secretase inhibitor RG6289 designed to block the formation of amyloid – both in phase 2.