Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment.

We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti-CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single-arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14. Subsequently, cusatuzumab was administered intravenously on days 3 and 17 at 20 mg/kg in combination with azacitidine (75 mg/m2 ) on days 1-7 of each 28-day cycle. All six participants had at least one treatment-emergent adverse event, and the most common treatment-emergent adverse events (all grades) were leukopenia (four participants [66.7%]) and constipation (three participants [50.0%]). No dose-limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants, and further exploration of this combination is warranted.

A 24-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of the rivastigmine patch in Japanese patients with Alzheimer's disease.

BACKGROUND: As of 2010, the rivastigmine patch was licensed for the treatment of Alzheimer's disease (AD) in 64 countries. METHODS: This 24-week, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy, safety and tolerability of the 5-cm(2) (9-mg loading dose; 4.6 mg/24 h delivery rate) and 10-cm(2) (18-mg loading dose; 9.5 mg/24 h delivery rate) rivastigmine patch in Japanese patients with AD. RESULTS: In the primary analysis population (intent-to-treat last observation carried forward) at week 24, delayed deterioration was seen with the 10-cm(2) patch versus placebo on the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog; p = 0.005) and the Japanese version of the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC plus-J; p = 0.067). Participants receiving the rivastigmine patch showed numerically less decline versus placebo at week 24 on the CIBIC plus-J, although this did not reach statistical significance. Statistical significance for the CIBIC plus-J was met following adjustment for body weight and baseline Mini-Mental State Examination score as dynamic allocation factors (p = 0.042) and on the Disability Assessment for Dementia (DAD; p = 0.024) and Mental Function Impairment (MENFIS; p = 0.016) subscales. Serious adverse events were rare and were consistent with the known safety profile of the rivastigmine patch. CONCLUSION: The rivastigmine patch has a favorable efficacy and tolerability profile in Japanese patients with AD.