Tilavonemab in early Alzheimer's disease: results from a phase 2, randomized, double-blind study.

Tau accumulation in patients with Alzheimer's disease tracks closely with cognitive decline and plays a role in the later stages of disease progression. This phase 2 study evaluated the safety and efficacy of tilavonemab, an anti-tau monoclonal antibody, in patients with early Alzheimer's disease. In this 96-week, randomized, double-blind, placebo-controlled study (NCT02880956), patients aged 55-85 years meeting clinical criteria for early Alzheimer's disease with a Clinical Dementia Rating-Global Score of 0.5, a Mini-Mental State Examination score of 22 to 30, a Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index score of ≤85, and a positive amyloid PET scan were randomized 1:1:1:1 to receive one of three doses of tilavonemab (300 mg, 1000 mg, or 2000 mg) or placebo via intravenous infusion every 4 weeks. The primary end point was the change from baseline up to Week 96 in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Safety evaluations included adverse event monitoring and MRI assessments. A total of 453 patients were randomized, of whom 337 were treated with tilavonemab (300 mg, n = 108; 1000 mg, n = 116; 2000 mg, n = 113) and 116 received placebo. Baseline demographics and disease characteristics were comparable across groups. The mean age was 71.3 (SD 7.0) years, 51.7% were female, and 96.5% were White. At baseline, the mean CDR-SB score was 3.0 (1.2), which worsened through Week 96 for all treatment groups. The least squares mean change from baseline at Week 96 in the CDR-SB score with tilavonemab was not significantly different compared with placebo [300 mg (n = 85): -0.07 (95% confidence interval, CI: -0.83 to 0.69); 1000 mg (n = 91): -0.06 (95% CI: -0.81 to 0.68); 2000 mg (n = 81): 0.16 (95% CI: -0.60 to 0.93); all P ≥ 0.05]. The incidence of any adverse event and MRI findings were generally comparable across groups. Tilavonemab was generally well tolerated but did not demonstrate efficacy in treating patients with early Alzheimer's disease. Further investigations of tilavonemab in early Alzheimer's disease are not warranted.

Current state of renal transplant immunosuppression: Present and future.

For kidney transplant recipients, immunosuppression commonly consists of combination treatment with a calcineurin inhibitor, an antiproliferative agent and a corticosteroid. Many medical centers use a sequential immunosuppression regimen where an induction agent, either an anti-thymocyte globulin or interleukin-2 receptor antibody, is given at the time of transplantation to prevent early acute rejection which is then followed by a triple immunosuppressive maintenance regimen. Very low rejection rates have been achieved at many transplant centers using combinations of these agents in a variety of protocols. Yet, a large number of recipients suffer chronic allograft injury and adverse events associated with drug therapy. Regimens designed to limit or eliminate calcineurin inhibitors and/or corticosteroid use are actively being pursued. An ideal immunosuppressive regimen limits toxicity and prolongs the functional life of the graft. This article contains a critical analysis of clinical data on currently available immunosuppressive strategies and an overview of therapeutic moieties in development.