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20-F
AC IMMUNE SA filed this Form 20-F on 03/21/2019
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ACI-24

 

ACI-24 is a vaccine candidate that is currently in a Phase 2 clinical study for AD after completing a Phase 1/2 clinical study in 2018. ACI-24 was developed utilizing our SupraAntigen platform, and is designed to stimulate a patient’s immune system to produce antibodies that specifically target the misfolded Abeta conformer to prevent plaque accumulation and to enhance plaque clearance. Pre-clinical data demonstrated significant activity in plaque reduction and memory restoration. ACI-24 has a favorable safety profile, characterized by a lack of observed local inflammation and a mechanism of action independent of inflammatory T-cells. ACI-24 is fully owned by AC Immune and has been developed in-house.

 

Phase 1/2 Study

 

Phase 1/2 Study Design

 

To be considered a Phase 1/2 study, a study or part of it must include as a primary goal the assessment of efficacy in a patient population, assessed using either clinical endpoints or biomarkers. This is in contrast to a Phase 1 study where the primary goal typically includes only safety and pharmacokinetic or pharmacodynamic measures.

 

The Phase 1 part of the combined Phase 1/2 study is completed and the clinical study report will be finalized in 2019. The efficacy, tolerability and immunogenicity of ACI-24 were tested in mild to moderate AD patients with four different doses in a randomized, placebo controlled, double blind study. The different doses were tested via an ascending dose design in four consecutive cohorts with 12 patients each (9 on active, 3 on placebo treatment). ACI-24 was administered by subcutaneous injection with multiple injections per cohort. The initial safety follow-up period for two years has been shortened to one year mainly for the patients of the last cohort.

 

Phase 1 Study Data

 

Safety and tolerability

 

Due to the observed favorable safety profile, the treatment free safety follow-up period of the Phase 1 part of the study was shortened to one year. Fourteen serious adverse events were observed in the phase 1/2 study. All events were considered to be unrelated to study treatment and included one malignant colon polyp; one wound infection associated with a planned hip replacement; one radius fracture; an intra-abdominal cancer of unknown origin followed by death of the patient; one fall complicated by vertebral compression fracture; one case of acute chest pain; one death due to AD; one death considered to be due to complications from coronary artery disease; one case of pneumonia; one case of breast cancer; three successive episodes of pancreatitis in addition to gallstones in one patient; and an inguinal hernia in one patient. One additional serious adverse event unrelated to study treatment (urinary retention leading to a hospitalization) has been reported in the phase 2 study which is currently ongoing. Until now, the ACI-24 vaccine is considered as safe and well tolerated.

 

Antibody response

 

Antibody responses were only observed in the two higher dose groups of cohort 3 and 4 indicating a dose dependent effect of the vaccine. No IgG antibody response was observed in placebo treated patients of those cohorts.

 

PET Imaging and cognitive measures

 

While the study was not powered to examine efficacy, a dose-dependent trend of reduction in accumulation in brain amyloid measured by PET imaging was observed in cohorts 3 and 4.

 

Due to the safety profile and potential dose dependent reduction of amyloid plaques as measured by PET imaging, we have moved this program forward into a Phase 2 clinical trial which is currently ongoing. In order to optimize the immune response, the route of administration has been switched to intramuscular, since this route was associated with better antibody responses in a preclinical study.

 

Phase 2

 

Phase 2 Study Design

 

The aim of the Phase 2 double-blind, randomized, placebo-controlled adaptive design study is to assess the safety, tolerability, immunogenicity and target engagement of ACI-24 formulations in patients with mild AD. The trial will seek to confirm the positive trends on Abeta PET imaging observed in the previous Phase 1/2 study. The Phase 2 trial is being conducted in several European countries and the first dosing occurred in October 2018 via the intramuscular route of administration.

 

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