Hospital Pharmacy - December 2017 - 738

738

Hospital Pharmacy 52(11)

Table 1. Beta Amyloid Plaque Reduction.
Sponsor

Route

Verubecestat

Merck & Co

Oral

Aducanumab

Biogen Inc

IV infusion

Lanabecestat
(AZD3293)

AstraZeneca and Eli
Lilly & Co

Oral

Crenezumab

F. Hoffmann-La
Roche AG

IV infusion

Gantenerumab

F. Hoffmann-La
Roche AG

Subcutaneous
injection

Elenbecestat

Eisai Co, Ltd, and
Biogen Inc

Oral

Comments
A BACE inhibitor. The Phase II/III trial was terminated in February 2017
in patients with mild-to-moderate AD after an external data review
committee determined the drug had no chance of positive outcomes. A
1500-patient, Phase III trial in patients with early AD is expected to be
completed in 2019.
A monoclonal antibody that binds to beta amyloid. Phase I data have shown
a reduction in amyloid plaque. Two Phase III trials will examine use of the
drug in patients with early disease.
A BACE inhibitor. A Phase I trial demonstrated a reduction in amyloid beta
proteins with lanabecestat. Two Phase III trials are currently active and are
evaluating efficacy in patients with mild AD. Both trials are expected to be
completed in 2019.
A monoclonal antibody that binds to beta amyloid. The drug failed to slow
a decline in cognition in 2 Phase II trials in mild-to-moderate AD patients
with a dose of 15 mg/kg. A Phase Ib trial found no safety issues with doses
up to 120 mg/kg, so 2 Phase III trials are underway in patients with early
AD using a dose of 60 mg/kg. Results from one of the trials are expected
in 2020.
A monoclonal antibody that binds to beta amyloid. A Phase III trial of
presymptomatic AD was stopped early when gantenerumab failed to
improve cognition. Two Phase III trials are underway in patients with early
or mild AD using a higher dose of gantenerumab.
Elenbecestat, a BACE inhibitor, decreased beta amyloid plaque in a Phase II
trial. A 1330-patient Phase III trial began in late 2016 in patients with early
AD and is expected to be completed in 2020.

Source. Information adapted from the Prescribe Right Pharmaceutical Pipeline Tracker database.7
Note. IV = intravenous; AD = Alzheimer's disease; BACE = Beta Secretase.

Table 2. Tau Protein Targeting Drugs.
Sponsor

Comments

LMTX

TauRx Therapeutics
Ltd

AADvac1

Axon Neuroscience
SE

ABBV-8E12

AbbVie, C2N
Diagnostics, LLC

LMTX is a small-molecule Tau aggregation inhibitor. LMTX failed to demonstrate a cognitive
improvement over placebo in 2 Phase III trials. The drug is now being tested in a new trial in
Alzheimer's patients who are not receiving cholinesterase inhibitors or memantine.
AADvac1 is active immunotherapy targeting Tau protein. In a 12-week, Phase I trial, AADvac1
induced an immunological response to pathological Tau proteins. No safety issues occurred
during the trial and cognition remained stable. Axon has completed enrollment in a 24-month,
Phase II trial, that is testing AADvac1 long-term safety and efficacy in patients with mild AD. The
trial is expected to be completed in 2019.
ABBV-8E12 is passive monoclonal antibody targeting Tau protein. In a Phase I trial, ABBV-8E12
was well tolerated with no major safety issues detected. A 180-patient, 96-week, Phase II trial in
400 patients with mild AD diagnosed is currently active with a primary outcome of decrease in
the Clinical Dementia Rating and adverse effects. The trial is expected to be completed in 2020.

Source. Information adapted from the Prescribe Right Pharmaceutical Pipeline Tracker database.7
Note. LMTX = leuco-methylthioninium-bis(hydromethanesulfonate); AD = Alzheimer's disease, ADAS-Cog 11 = Alzheimer's Disease Assessment Scale;
ADCS-CGIC = Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change Scale

of the disease. Researchers have also been testing antibodies
that bind to beta amyloid proteins (Table 1) as another way to
reduce accumulation.

Tau Protein Targeting Drugs
Because of disappointments with BACE inhibitors, Tau protein
targeting drugs (Table 2) are becoming the new hope to finally

solve AD. Tau protein is a protein responsible for maintaining
the structure of neurons by supporting microtubules.5 In AD,
the Tau protein becomes hyperphosphorylated and begins to
form tangles.5 These tangles can cause the neurons to lose their
ability to communicate and to receive nutrients causing the
neuron to decay and degenerate.5 This loss of neuron function
is what many believe to be one of the leading causes of AD.
Leuco-methylthioninium-bis(hydromethanesulfonate)

Table of Contents for the Digital Edition of Hospital Pharmacy - December 2017