Icad antibody trial#
Icad antibody free#

Siemers briefly mentioned brain imaging with IMPY in this trial. вЂњTo us it suggests that the plaques are beginning to dissolve and AОІ42 slowly leaves the brain.вЂќ Siemers said further that at the time of spinal tap, all injected antibody is saturated with AОІ, so that additional AОІ42 coming off the plaques would stay free. What does this mean? вЂњWe had to think about this,вЂќ Siemers said. (CSF AОІ42 concentrations are low in people with AD.) According to the poster, the AОІ40 drop happened in the 3,000 picogram/ml range, the AОІ42 rise in the 200 picogram/ml range.

Icad antibody free#

At ICAD, they reported that the unbound, i.e., free, CSF AОІ40 decreased with greater doses of antibody, whereas the free CSF AОІ42 increased with rising doses of antibody. The Lilly scientists developed assays to distinguish in CSF between free AОІ and AОІ bound to antibody, doing so separately for AОІ40 and 42. There, too, total AОІ40 and 42 concentrations increase up to four orders of magnitude in a dose-dependent way, Siemers reported. The scientists showed a graph with different-sized saw tooth zigzag lines of plasma AОІ levels curving up in response to each injection, and they calculated the pharmacodynamics to conclude that monthly injections would be acceptable for Phase 3.ДЄ tiny fraction, some 0.1 percent, of the antibody crosses into the CSF.

Icad antibody trial#

If the antibody is so safe, is it doing anything at all? In plasma, it caused both AОІ40 and 42 concentration to shoot up several orders of magnitude, as was also seen in the Phase 1 trial of this compound (see ARF Keystone story). вЂњThe safety data could not be better,вЂќ Siemers told this reporter. Five of the patients, four of them dosed weekly, showed antibody titers to LY2062430, but these titers had no detectable effects. None of the 42 treated patients showed evidence of edema, microhemorrhage, inflammation, nor were there laboratory abnormalities or troubling signs of immune response. On safety, Siemers said that no side effect cropped up that could be attributed to the antibody. It also measured ADAS-Cog at the beginning and at 12 weeks, did plasma and CSF research, and a little neuroimaging. The trial assessed its primary outcome of safety by looking for host immune responses against the Lilly antibody and for fluid or inflammatory signals by MRI and CSF, in addition to the usual adverse event monitoring. The study was recently locked for definitive analysis, Siemers said. At ICAD, Siemers showed interim data from day 112/week 16, i.e., partway into the follow-up period. The injections and most assessments ended at week 12, but patients will be followed for a year. The patients received 12 weekly infusions of placebo or antibody arranged to contain either 100 mg every four weeks, 100 mg every week, or 400 mg every four weeks, or 400 mg every week. The Phase 2 trial tested four different doses of LY2062430, a therapeutic antibody, in people with mild to moderate AD in order to determine which doses and which interval between doses to use in Phase 3. Here are the details:ДЄt ICAD, Eric Siemers and Ron DeMattos of Eli Lilly and Company in Indianapolis separately presented results of the trial and its attendant biomarker research, respectively. Safety and biomarkers, but not efficacy, are also what drove Lilly's Phase 2 testing of its Оі-secretase inhibitor, which is currently enrolling for Phase 3 (see Fleisher et al., 2008). It instead ran a small and short (52 patients/3 months) Phase 2 trial that was heavily geared toward fluid biomarkers, and used those results as the basis to move into Phase 3 by 2009. But rather than running a sizable and long Phase 2 trial (230 patients/19 months in the case of Elan/Wyeth), and scrutinizing its results for hints for efficacy (see ARF ICAD story), Lilly decided to sidestep clinical efficacy entirely. Elan/Wyeth uses a humanized version of an N-terminal AОІ antibody that recognizes forms of AОІ peptide in amyloid plaques Lilly uses a mid-region antibody (m266) that captures soluble AОІ and tests the peripheral sink hypothesis of AОІ clearance ( DeMattos et al., 2002). Both competitors are developing a humanized therapeutic antibody, which would be the first biologic treatment for AD. At the International Conference on AlzheimerвЂ™s Disease, held 26-31 July in Chicago, the pharmaceutical company Eli Lilly and Company took the opposite approach to Elan/Wyeth. At this juncture, they sometimes base the decision on whether to start a long and costly Phase 3 program on less than rock-solid efficacy data (see ARF ICAD story). As new experimental drugs are getting ready for clinical testing against Alzheimer disease, itвЂ™s instructive to learn how pharmaceutical companies are navigating the transition from Phase 2 to 3.