AstraZeneca’s BACE inhibitor AZD3293 has passed Phase 1 safety tests and will enter a large international Phase 2/3 trial later this year, said Samantha Budd from the company’s Cambridge, Massachusetts, site. The news comes after Merck’s December 2013 announcement that its inhibitor MK-8931 had cleared safety hurdles in its Phase 2/3 study (see Dec 2013 news story). Other BACE inhibitors are in earlier stages of development.
AstraZeneca is finalizing the design of the Phase 2/3 trial through discussions with regulatory agencies in the United States, Europe, and Japan, Budd said. Although the details remain to be ironed out, the 24-month trial will include at least 1,000 people in the early stages of the disease. “We believe that β-secretase inhibitors are likely to be more effective the earlier we test,” Budd noted. Participant selection will be based on amyloid deposition in the brain, as judged by cerebrospinal fluid Aβ levels or PET amyloid imaging. The researchers will use clinical endpoints as well as fluid and imaging biomarkers as outcome measures.
In Phase 1 studies, AZD3293 lowered Aβ in cerebrospinal fluid (CSF) by as much as 75 percent, with levels taking two to three weeks to return to baseline after treatment, Budd reported at the Sixth Clinical Trials Conference on Alzheimer’s Disease (CTAD) held November 14-16, 2013, in San Diego. The company will present safety and tolerability data from these trials at the 13th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, to be held March 26-29 in Geneva.
Several other BACE inhibitors have fallen by the wayside, including Eli Lilly and Company’s LY2886721 (see Jun 2013 news story) and Roche’s RG7129. In 2012, Takeda Pharmaceutical Company in Osaka, Japan, handed off its BACE inhibitor TAK-070 to the University of Tokyo for use in clinical research (see company press release). Takeda no longer develops the compound, but will receive royalties if the university commercializes the drug. Eisai Co., Ltd., also based in Japan, recently completed Phase 1 studies of its inhibitor E2609 in healthy volunteers and AD patients.—Madolyn Bowman Rogers.
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