LY2886721 has a number of competitors, including MK-8931 from Merck MRK and Ligand Pharma LGND. As you'll see in the data below, the Lilly drug is inferior to MK-8931 in terms of the reduction of CSF levels of AB1-40 (alpha-beta 1-40) peptide after 14 days of treatment (maximum decline of 74% vs. 94%). Of course we have a long way to go before we have any idea if either drug will be effective in treating Alzheimer's disease.
Click here for data from four abstracts on MK-8931 presented at the 2012 AAIC meeting (see where the 94% figure came from...)
[P01.017] Pharmacokinetic (PK) and Pharmacodynamic (PD) Effects of BACE Inhibitor LY2886721 in Healthy Volunteers (HVs) at Steady State
Ferenc Martenyi, Indianapolis, IN, Brian A. Willis, Indianapolis, IN, Robert Dean, Indianapolis, IN, Celedon R. Gonzales, Indianapolis, IN, Stephen F. Komjathy, Indianapolis, IN, Scott Monk Monk, Indianapolis, IN, Stephen L. Lowe, Singapore, Singapore, Leslie L. Daugherty, Indianapolis, IN, Masako Nakano, Kobe, Japan, Dustin J. Mergott, Indianapolis, IN, Patrick May, Indianapolis, IN
OBJECTIVE: To evaluate peripheral and central PK/PD for LY2886721 at steady state in healthy subjects.
BACKGROUND: LY2886721, a potent BACE inhibitor, dose-dependently lowers Aβs in animals and humans.
DESIGN/METHODS: PK and PD were assessed with daily oral LY2886721 or placebo administration for 14 days in HVs in two trials: A Multiple Ascending Dosing (MAD) with 5, 15 and 35 mg and a second Single Dose followed by MAD with 70 mg LY2886721. CSF was obtained by LP at baseline and 24 hours after last 14 day dose. Plasma (single dose, multiple dose) and CSF (multiple dose) LY2886721 concentrations were measured by LC/MS/MS. Plasma and CSF Aβ1-40, Aβ1-42 , Aβ1-X and CSF sAPPβ and sAPPa were measured by immunoassay. Adverse events, vital signs, electrocardiograms, labs and eye exams were assessed.
RESULTS: LY2886721 appeared safe and well tolerated in 47 HVs completing the studies. The t1/2 of LY2886721 is approximately 12 hours. LY2886721 produced dose-dependent lowering of plasma Aβ1-40 compared to baseline The 24-hour time-averaged change from baseline (TACFB) in plasma Aβ1-40 after 14-day dosing with placebo, 5, 15, 35 and 70mg LY2886721 Aβ1-40 was -3.18, –51.8, –63.6,–76.9 and -82.9 %, respectively. The 35 and 70 mg doses were associated with >80% plasma Aβ1-40 reduction at nadir and levels did not return to baseline at 168 hours after any investigated dose. The change in CSF Aβ1-40 was –2.1–12.5, –30.8, –57.8, and –74.4 % respectively. LY2886721 administration for 14 days at 70 mg also significantly decreased CSF Aβ1-42 (-71.1%), sAPPβ (-77.2 %), and increased CSF sAPPα (+58.9%). CONCLUSIONS: Good safety and tolerability profile and robust central PD effects of LY2886721 have been established in HVs. Further investigation of LY2886721 is ongoing in Phase 2 clinical trials of patients with mild AD and MCI due to AD. Supported by: Lilly Research Laborarories.
Category - Aging and Dementia: Clinical Trials
Monday, March 18, 2013 2:00 PM
Session P01: Aging and Dementia: Therapeutics and Clinical Trials (2:00 PM-6:30 PM)