Thursday, July 19, 2012

Eisai Presents Phase I data on its BACE Inhibitor - E2609

At Alzheimer Association International Conference, Eisai presented Phase I data on its BACE inhibitor. The data confirms the effect of BACE inhibtion on Aβ production.  The two E2609 Phase I studies presented at the AAIC 2012 comprised a single oral ascending dose study (Study A001-001) which showed Aβ levels reduction in plasma, and a 14-day multiple oral ascending dose study (Study A001-002) which showed dose-dependent increase of E2609 PK level and statistically significant reduction of Aβ levels in cerebrospinal fluid (CSF).

Study A001-001 was a randomized, double-blind, placebo-controlled, single ascending dose study
conducted in 73 healthy adult volunteers. Subjects were divided into nine cohorts to receive E2609 doses
of between 5 mg to 800 mg. Plasma Aβ [Aβ(1-x)] levels were measured prior to patients receiving E2609
and then at multiple time points up to 144 hours post-dose. The maximum dose-dependent reduction of
plasma Aβ(1-X) relative to baseline was 52% at 5 mg, and 92% at 800 mg.

Study A001-002 was a randomized, double-blind, placebo-controlled, multiple ascending dose study
conducted in 50 healthy adult volunteers. Subjects were divided into five cohorts, with each cohort
receiving E2609 doses of between 25 mg and 400 mg per day for 14 days. The study measured Aβ levels
both in plasma and CSF. Preliminary interim analysis results showed that E2609 demonstrated a clear
reduction in plasma Aβ(1-X) level (See Figure I) and a dose-dependent reduction in CSF Aβ(1-X) (See
Figure II) in subjects who received daily doses of between 25 mg and 200 mg. The percentage decrease
in CSF Aβ(1-x) after 14 days dosing compared to baseline was statistically significant, with E2609
demonstrating a 46.2%, 61.9%, 73.8% and 79.9% difference in percentage decrease compared to
placebo in the 25 mg, 50 mg, 100 mg and 200 mg cohorts, respectively.

No clinically significant safety concerns were observed following repeated oral dosing of up to 200 mg. Several cases of orolabial herpes relapse were observed in the 200 mg cohort, however, while being evaluated, the significance of these cases is unknown as the blind remains unbroken on the safety data