AC Immune reports ACI-35.030 advances into Phase 2b trial

AC Immune (ACIU) announced that its development partner has programmed the launch of a Phase 2b clinical study to evaluate ACI-35.030 in patients with preclinical Alzheimer’s disease, those individuals not yet showing symptoms. ACI-35.030 is an investigational targeted active immunotherapy, selective for pathological phosphorylated Tau. Studies have shown that pTau correlates with AD progression and the trial aims to show that ACI-35.030 can prevent or slow down the progression of tau pathology and onset of clinical symptoms. Under the terms of the licensing agreement with Janssen Pharmaceuticals, a Johnson & Johnson company (JNJ), AC Immune will now receive a milestone payment of CHF 15M and will receive another milestone payment of CHF 25M related to achieving a non-disclosed enrollment target. The partnership with Janssen aims to develop and commercialize therapeutic anti-Tau active immunotherapies for the treatment of AD and potentially other Tauopathies. The Phase 2b ReTain trial is a potentially registration-enabling trial and is a randomized, multicenter, double-blind, placebo-controlled clinical study in participants with preclinical AD to assess the clinical effect of active immunization with ACI-35.030. It is designed to test the hypothesis that ACI-35.030 has a disease-modifying effect that can delay or prevent the onset of cognitive impairment or other clinical symptoms in individuals with preclinical AD through inhibition of seeding and spreading of pathological Tau. Approximately 500 participants with preclinical AD will be randomized in a 1:1 ratio to a single dose level of ACI-35.030 or placebo and administered as intramuscular injections for a maximum of 4 years. The primary endpoint will measure cognitive decline as assessed by the Preclinical AD Cognitive Composite 5 score, which combines tests that evaluate episodic memory, timed executive function, and global cognition. It is sensitive enough to detect early changes in cognitive function, even before the first clinical signs of mild cognitive impairment are apparent. The key secondary efficacy endpoint will assess the effect of ACI-35.030 on the propagation and/or accumulation of Tau pathology compared with placebo, as measured by Tau PET imaging in the Tau Naive Composite region of interest. PET imaging for pathological Tau will be performed at baseline and annually for 4 years. This endpoint may be sufficient for a Biologics License Application filing seeking accelerated approval from the U.S. Food & Drug Administration, with the primary endpoint serving as the basis for a traditional approval.