24 May 2007. Elan and Wyeth announced on 21 May that they are planning to initiate a U.S. phase 3 clinical trial of AAB-001 (bapineuzumab) for the treatment of mild to moderate Alzheimer disease patients even before phase 2 is complete (see Elan Press Release). Bapineuzumab is a humanized monoclonal antibody that binds to and clears Aβ peptide and has been fast-tracked by the Food and Drug Administration. Referred to as passive immunotherapy, this therapeutic approach delivers anti-Aβ antibodies directly to the patient, rather than inducing patients to mount their own individual immune response to injected Aβ peptide. The hope is that eliminating an active immune response may avoid the serious side effects that were previously observed in the suspended phase 2 trial of AN-1792, in which patients were immunized with Aβ peptides. The active immune response resulted in encephalitis (cerebral inflammation) in 6 percent of patients. Elan and Wyeth believe that the benefits demonstrated with AN-1792 will be similar with AAB-001, but that AAB-001 will be safer. Unlike the active immunization approach, however, treatment of AD by passive immunotherapy would require regular injections of antibody.
The phase 3 trial is scheduled to begin in the second half of 2007, pending the finalization of study design and approval by regulatory agencies. A blinded phase 2 efficacy study of AAB-001 is ongoing, and is scheduled to be completed in 2008. The decision to initiate phase 3 prior to the completion of phase 2 is unusual. According to an Elan spokesperson, it is based on a recent review of all clinical data that Wyeth and Elan have compiled on the efficacy of AAB-001. This includes phase 1 and phase 2 studies of AAB-001, as well as a 4.5-year follow-up study of the patients who had started the AN-1792 study (ARF conference news; further extension of this data, with similar trends, was reported at the 8th International Conference AD/PD last March in Salzburg, Austria). A scheduled interim look at data from the ongoing AAB-001 phase 2 was also part of this review. In the companies’ eyes, these clinical data taken together reveal a meaningful trend in efficacy. The endpoints scored to arrive at this conclusion include ADAS-Cog (see ADAS-Cog) to assess cognitive function, Neuropsychological Test Battery (see CANTAB) to evaluate memory, attention, and executive function, and Disability Assessment for Dementia (DAD), to measure quality of life.—Gwen Wong.