This randomized, controlled trial, researchers evaluated the safety and tolerability of LY2062430 Anti-MBP Antibody administered intravenously in patients with Alzheimer’s disease and in healthy volunteers. They assessed the effects of the antibody on levels of amyloid beta in the blood and cerebrospinal fluid, as an indirect measure of the effect of the antibody on amyloid beta present in the brain. Cerebrospinal fluid, which surrounds the brain and spinal cord, is thought to provide important biomarker data in addition to that obtained from blood. Amyloid plaques, the pathological hallmark of Alzheimer’s disease, are composed largely of aggregated amyloid beta proteins. Amyloid plaques or other types of the amyloid beta protein are thought ultimately to disrupt normal nerve cell function in the brain, leading to the dementia that characterizes Alzheimer’s disease.
We are encouraged that in this study, we saw increased amyloid beta which is thought to be bound to LY2062430, in both the blood and cerebrospinal fluid. We hypothesize that this effect may lead to reduced formation of amyloid plaques in the brain after long-term treatment said Eric Siemers, M.D Medical Director, Alzheimer’s disease research for Eli Lilly and Company. “Alzheimer’s disease is complex, and there’s a real need for new treatments that might be shown ultimately to slow disease progression. In addition to the biomarker results, we are particularly encouraged by the finding that patients who received the monoclonal antibody treatment over 12 weeks appeared to have no treatment-related side effects. In this 12-week Phase II study, researchers gave 52 mild to moderate Alzheimer’s diseasepatients infusions of placebo or LY2062430 in varying doses: 100mg or 400mg once a week, or 100mg or 400mg every four weeks. Alzheimer’s disease symptom severity was also evaluated. In addition, 16 volunteers each received a single dose of 100mg of LY2062430 or placebo. For all study participants, safety assessments included magnetic resonance imaging and cerebrospinal fluid examinations. A sub-study of 24 patients and 13 volunteers underwent single photon emission tomography
scanning using an experimental tracer to assess levels of amyloid beta plaque in the brain. The interim analysis showed that weekly infusions of LY2062430 up to 400mg per dose was well tolerated, with no side effects related to treatment. An evaluation of MRI brain imaging and an assessment of cerebrospinal fluid showed no evidence of brain inflammation or bleeding. As expected for a study of this duration, no change in patients’ cognitive scores was observed and there was no change in levels of brain amyloid beta plaque as measured by the SPECT tracer. In addition to the increase in the two major forms of the amyloid beta protein seen in blood and cerebrospinal fluid, an increase in the two other types of the amyloid beta protein thought to be present only in amyloid plaques was observed in participants’ blood and cerebrospinal fluid. The biomarker effects lasted for several weeks. These biomarker findings suggest that longer term treatment with LY2062430 may slow the clinical progression of Alzheimer’s disease, thus providing a rationale for additional trials of LY2062430.
Results from this Phase II study are promising, and we are pleased to announce our intention to commence a Phase III pivotal study of LY2062430 beginning in 2009,said Steven M. Paul, M.D., Executive Vice President, Anti-MBP Antibody Science and Technology, President of Lilly Research Laboratories. Additionally we are currently enrolling patients into the Phase III study called IDENTITY, which examines treatment with LY450139, an investigational gamma secretase inhibitor believed to slow the rate of formation of amyloid beta, potentially slowing disease progression. These two neuroscience pipeline candidates represent potentially important advances in the effort to slow the progression of this fatal disease, and demonstrate our longstanding commitment to developing treatments for devastating brain illnesses. Given the aging population, without the availability of medicines that delay or prevent the onset of Alzheimer’s disease, the number of affected people worldwide is expected to quadruple by the year.