AAN 2015: conference highlight

Good news for Alzheimer’s Disease underscores the principle of treating early in neurodegeneration. #AAN2015 #MSBlog #MSResearch

“Many people have asked me what was my highlight of the AAN 2015 meeting. To be honest it was not MS-related data, but early data from a phase 1b/2a study of a new monoclonal antibody, aducanumab, that targets the so called A-beta protein in early Alzheimer’s Disease (AD). The study was a safety and dose finding study of an antibody that targets a specific protein aggregate that is found in AD and is hypothesised to cause the disease. The study showed a dose response (see figure below) and, despite its small size, had an effect on cognition. Other studies using this approach have failed. Why? This study was in ADers with very early or asymptomatic disease; targeting the pathology before you have frank dementia may be the secret to why this study was positive. Another reason may be that aducanumab is simply better at neutralising toxic species of the A-beta protein, the so called oligomers, than the other similar antibodies studied to date.”

“Why is this study important to MSers? It reinforces the therapeutic principle in neurodegenerative diseases, MS included, that if want to target the neurodegenerative diseases you need to do so in the so called presymptomatic phase. In other words we should be targeting progressive MS before it becomes clinically apparent. The other reason it is important to MSers is that if we do our jobs properly and look after you brain you may be susceptible to the development of AD in the future. It is estimated  that 1 in 3 of us who live long enough will get AD. Therefore you may need to be treated for AD in  the future. I have scoured the literature and I am not sure if anyone has described AD pathology in MS. I suspect it is because nobody has done a systematic look.”

“It is early days and it is clear that this data will now form the basis of a large clinical development programme in AD.”

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Objective: Aducanumab (BIIB037) is a human monoclonal antibody selective for aggregated forms of beta‐amyloid peptide being investigated as a disease‐modifying treatment for AD.

Background: This Phase 1b study is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of aducanumab in patients with prodromal or mild AD.

Design/Methods: Patients included in this multicenter, randomized, double‐blind, placebo‐controlled, multiple‐dose study (PRIME; NCT01677572) were aged 50‐90 years, had a positive florbetapir (18F‐AV‐45) PET scan, and met clinical criteria for prodromal or mild AD. During the double‐blind, placebo‐controlled phase, patients received aducanumab or placebo once every 4 weeks for 52 weeks. In a staggered, ascending‐dose design, patients were randomized to 1 of 7 treatment arms stratified by ApoE4 status (carrier/non‐carrier). We present results from an interim analysis (after subjects in all arms completed at least the Week 26 visit) on safety and change in florbetapir PET signal by disease stage and ApoE4 status.

Results: Patients (N=166) were randomized to placebo (n=40), 1 (n=31), 3 (n=33), 6 (n=30) or 10 (n=32) mg/kg aducanumab. Of 165 patients dosed, 65% were ApoE4 carriers (35% non‐carriers) and 41% had prodromal AD (59% mild). The incidence (based on MRI) of the most common AE (amyloid‐related imaging abnormalities [ARIA]) was dose‐ and ApoE4‐status?dependent (for ARIA‐edema or ‐microhemorrhage or ‐hemosiderosis: ApoE4 carriers, 11%, 14%, 43% and 65% for 1, 3, 6 and 10 mg/kg aducanumab, respectively, versus 8% for placebo; ApoE4 non‐carriers, 8%, 18%, 11%, and 17% versus 0%). Treatment‐related dose‐ and time‐dependent reductions in brain beta‐amyloid plaque (shown by SUVR reduction) at Weeks 26 and 54 were consistent across mild and prodromal subgroups and across ApoE4 carriers and non‐carriers within the doses tested.

Conclusions: ARIA was the main safety and tolerability finding and was dose‐and ApoE4‐dependent. Aducanumab reduced beta‐amyloid plaque across mild and prodromal stages, and ApoE4 carriers and non‐carriers. 

 Study Supported By: Biogen Idec Inc and Neurimmune Holding AG

2 thoughts on “AAN 2015: conference highlight”

  1. I would imagine that because many of us get regular MRIs, our neuros will see AD in us earlier than in most. It would be the equivalent of RIS in MS. So we would have the advantage of getting some of the earliest treatment if it were available.

  2. I think that if MS is relabelled as dementia then it will add greater momentum too our cause and further industrial incentive. It will be regarded as Young Person's Dementia and will get the public's attention.We need a sea change.

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