AC Immune: Phase 2 substudy to increase understanding of familial Alzheimer’s

AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, today announced that Genentech, a member of the Roche Group, has initiated a substudy in the ongoing Phase 2 Alzheimer’s Prevention Initiative (API) trial of AC Immune’s investigational candidate, crenezumab. The substudy, which measures Tau burden using Positron Emission Tomography (PET), aims to increase the understanding of disease progression in the preclinical stage of autosomal dominantly inherited Alzheimer’s disease (familial AD).

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: “Learning more about the early distribution and severity of Abeta- and Tau-related pathology in AD is imperative in developing successful Alzheimer’s treatments. This new substudy will provide further evidence on the progression of familial AD by monitoring for changes in Tau burden and help examine the potential role of crenezumab as a disease-modifying agent that may prevent the onset or slow progression in people at risk of developing familial AD.”

The substudy will evaluate the effect of crenezumab, an anti-Abeta antibody, on the longitudinal Tau burden in a subgroup of presymptomatic Presenilin1 (PSEN1) E280A mutation carriers and non-carriers enrolled in API, a landmark study in Colombia to slow or prevent the decline of cognitive and functional abilities in people at risk of developing familial AD. The PSEN1 E280A mutation (or Paisa mutation) is by far the most common cause of familial early onset Alzheimer’s disease. Tau proteins are abundant in neurons and Tau pathology, or Tauopathy, spreads with a characteristic spatiotemporal pattern throughout the brain, coinciding with both clinical symptoms and disease progression in AD.

The API trial in Colombia, which began in 2013 and for which data are expected in the first quarter of 2022, is in cognitively healthy individuals with an autosomal dominant PSEN1 E280A mutation, which puts them at high risk of developing familial AD. This study will determine whether treating people carrying this mutation with crenezumab prior to the onset of AD symptoms, will slow or prevent the decline of cognitive and functional abilities. The new substudy will further improve the understanding of how Tauopathy may be used to track disease progression, including potential efficacy in people who may respond to treatment.

Participants in the new substudy will receive up to three intravenous injections of Genentech Tau Probe 1 and will undergo a Tau PET scan after each injection. The primary outcome measure will be change over time in Tau distribution, measured at week 130 up to week 260 of the main study.

“Treating earlier and testing in homogeneous populations are two important elements in AC Immune’s Roadmap to success and, both strategies are being applied in the API trial. Testing therapeutics in a homogeneous group in people carrying the PSEN1 E280A mutation earlier in the preclinical development phase, may make it possible to identify successful treatment strategies for treating this debilitating disease,” added Prof. Pfeifer.

It has been reported that many leaders in the field remain convinced that beta amyloid plays an important role in the initiation of AD. It is widely believed to be possible that studies to date have not intervened early enough or during the period before patients become symptomatic. As such, there may be an opportunity for early intervention with an investigational therapy such as crenezumab.