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New Alzheimer Drugs: 2 from AAN '15 You Shouldn't Miss

These two new drugs for Alzheimer disease, presented at AAN 2015, are too good not to review. Here, a 6-slide summary of aducanumab and encenicline studies.

Outside of the cholinesterase inhibitors, the main class of drugs available to slow the cognitive decline of Alzheimer disease, patients and physicians have little choice of treatment.On stage at the 2015 American Academy of Neurology Annual conference in April, however, were results of 2 early-phase trials, one with a monoclonal antibody (phase 1B) found to reduce beta-amyloid plaque and the other with a nicotinic agonist (phase 2b) that improved both memory and cognitive function. Both posters generated cautious optimism about the future for AD patients.Click through the 6-slide summary above for study highlights.

New drugs for Alzheimer disease

Two early-phase trials presented at the 2015 American Academy of Neurology Annual Conference were received with cautious optimism: Aducanumab (phase 1b), a monoclonal antibody, was found to reduce beta-amyloid plaque and the nicotinic agonist encenicline (phase 2b) improved both memory and global function.

Aducanumab shows promise in phase 1b trial

Investigators performed a randomized, double-blind, placebo-controlled, multi-dose phase 1b trial. Dosed patients (n=165) were aged 50-90 years and had positive florbetapir PET scan and clinical signs of prodromal (41%) or mild Alzheimer’s disease (59%). Based on ApoE4 status (65% carriers, 35% non-carriers), patients were randomized to: placebo (n=40) or 1 mg (n=31), 3 mg (n=33), 6 mg (n=30) or 10 mg (n=32) per kg aducanumab

Aducanumab decreases beta amyloid plaques

PET studies looking at standardized uptake value ratio (SUVR, which measures amyloid burden), showed treatment-related reductions in beta amyloid plaque at weeks 26 and 54. These reductions were time-and dose-dependent, and consistent for mild and prodromal subgroups, as well as for ApoE4 carriers and noncarriers. MRI studies showed the most common adverse events depended on dose- and ApoeE4 status. CONCLUSIONS: Aducanumab decreased beta amyloid plaque in mild and prodromal AD, and in ApoE4 carriers and noncarriers. The main safety and tolerability findings were related to ARIA, which depended on dose and ApoE4 status.

Encenicline improves cognition, function in phase 2b trial

Encenicline (EVP-6124)* is being develop to treat cognitive impairment in AD, schizophrenia. Agent partially agonizes nicotinic receptors, increasing response to acetylcholine and ultimately helping to improve cognition. Mild-to-moderate AD patients (N=409) were randomized to placebo, or to encenicline 0.27, 0.9, or 1.8 mg. Patients were divided into 2 groups: de-novo (not receiving an acetylcholintesterase inhibitor),or add-on (receiving donepezil or rivastigmine); ognitive (ADAS-Cog-13), clinical function (CDR-SB), and QOL evaluations performed every 4 weeks for 6 months.

High dose, de novo encenicline treatment saw better results

The 1.8 mg group experienced the most significant cognitive improvement, compared to placebo (p<.05) De novo patients experienced greater cognitive improvement than add-on patients (p<.05) Treatment-emergent adverse events were common (46% of patients): with higher dosage (0.27 mg, 42.3%, 0.9 mg, 48.5%, 1.8 mg, 53.0%; placebo, 40.4%); in the add-on group vs. de novo (56.7% vs 36.3%, respectively). Conclusion: Treatment with encenicline resulted in significant improvement in cognition and global functioning, especially among the 1.8 mg group and among de novo patients. The drug was “generally well tolerated,” and a phase 3 study has begun.

Aducanumab, encenicline show promise for Alzheimer treatment

Aducanumab take-home: Aducanumab decreased beta amyloid plaque in mild and prodromal AD, and in ApoE4 carriers and noncarriers. The main safety and tolerability findings were related to ARIA, which depended on dose and ApoE4 status. Encenicline take-home: Treatment with encenicline resulted in significant improvement in cognition and global functioning, especially among the 1.8 mg group and among de novo patients. The drug was “generally well tolerated,” and a phase 3 study has begun.

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