Paper Alert: Aducanumab Phase 1b Study Published
..."Lon Schneider of the University of Southern California in Los Angeles could have done without the tentative cognitive findings altogether. For one thing, he pointed out that the placebo group, which was pooled into a single group in the analyses, actually represented three groups that were randomized at different times. “They called it a ‘staggered parallel-group design,’ but really the cohorts were separate parallel-group studies occurring at different times and differing sites,” Schneider wrote to Alzforum. “Without the display of the cognitive data by dosing cohort, one has to wonder whether the apparent CDR-SB and MMSE benefits at 10 mg/kg had to do with variable baselines between cohorts and sites, statistical corrections, or extreme comparisons,” he wrote. Other researchers have expressed similar caution (see
Nov 2015 conference news)."
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On safety, the main concern was the dose-dependent ARIA-E, which predominantly affected carriers of the ApoE4 allele. While no one in the placebo group had ARIA-E, it manifested in one (3 percent), two (6 percent), 11 (37 percent), and 13 (41 percent) patients on 1, 3, 6, and 10 mg/kg aducanumab, respectively. A third of those people experienced clinical symptoms associated with ARIA-E, such as headaches. ARIA-E generally emerged in the early days of treatment, and resolved four to 12 weeks later. Nobody who had ARIA-E was hospitalized, and more than half of these participants continued treatment. However, the greatest drop-out rate (38 percent) occurred in the highest dose group, possibly due to the larger number of ARIA-E cases in that group. A quarter of patients in the placebo group discontinued treatment, compared to 23, 19, 17, and 38 percent in the 1, 3, 6, and 10 mg/kg groups, respectively.
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John Hardy of University College London expressed cautious optimism about the findings. “This was not a Phase 3 study: It was not powered or designed to identify treatment effects, and, even in the context of apparently positive data, we need to consider the possibility of selective subject drop-out and chance as underlying the positive findings. These new data are tantalizing, but they are not yet definitive.”
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http://www.alzforum.org/news/research-news/paper-alert-aducanumab-phase-1b-study-published
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