Pharmacokinetic evaluation of donanemab for the treatment of Alzheimer's.

INTRODUCTION: Donanemab is a humanized monoclonal antibody that significantly reduces cerebral amyloid plaques in Alzheimer's Disease (AD). It can delay disease progression and cognitive decline, making it one of the most promising disease-modifying treatments in the current treatment landscape. AREAS COVERED: This paper covers the current literature available on pharmacokinetics, pharmacodynamics, safety, and tolerability of donanemab. Publications from PubMed and Google were reviewed. A summary of regulatory approvals and current clinical data is also provided. EXPERT OPINION/COMMENTARY: Donanemab as a therapy for AD has more effective disease-modifying effects compared to lecanemab. Donanemab appears generally well-tolerated; however, it may have higher rates of severe side effects, such as amyloid-related imaging abnormalities (ARIA), that could lead to death. Guidelines for frequency of MRI monitoring for ARIA/safety are pending but will be integral to determining its use. Despite some limitations, donanemab is expected to receive FDA approval, giving clinicians access to another disease-modifying drug. Overall, more data is needed about donanemab, especially relating to safety, efficacy, cost, and integration with other treatments, but its development signifies progress in AD treatment.

Alzheimer's Disease (AD) is a brain disorder that severely impacts memory, behavior, and thinking. The most common treatments manage symptoms but do not slow disease progression or improve function. Accumulation of proteins called amyloid-beta plaques in the brain are one of the main causes of the disease. Donanemab is an antibody that helps the body remove these plaques. This review summarizes what is currently known about the safety of donanemab, how it works, and the extent to which it can help people with AD.Results suggest that donanemab significantly decreases the amount of plaques in the brain, delays disease progression, and improves cognition. Treatment can prevent reaccumulation of plaques for an extended period of time. There are some side effects associated with treatment, but they are generally manageable and resolve when the drug is stopped. In rare cases, more serious side effects were reported. These require careful monitoring and an evaluation of potential risk compared to benefit. Overall, current information on donanemab is extensive and shows promise. However, to help caregivers and people with AD make informed decisions on using the drug, further research is needed to fully explore donanemab's safety, cost, and efficacy compared to other therapies in the same class.

Profiling lecanemab as a treatment option for Alzheimer's disease.

INTRODUCTION: In July 2023, the U.S. Food and Drug Administration (FDA) granted full approval to lecanemab for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD dementia. Considering the limited treatment options for AD, the approval of lecanemab offers hope and opens the door for other disease-modifying therapies in the pipeline. AREAS COVERED: In this review, the authors summarize the FDA treatment guidelines, other anti-amyloid agents, and drug information relevant to prescribers, such as pharmacology and pharmacokinetics. Relevant clinical trial outcomes are discussed along with their significance and controversies. EXPERT OPINION: While questions remain about the magnitude of lecanemab's clinical impact, its approval signifies major progress in addressing the underlying pathology of AD. The authors have confidence in lecanemab as a promising treatment option and foresee exciting advancements on the 5-year horizon. Yet, further research is needed regarding trials beyond 18 months, post-marketing surveillance, and lecanameb in combination with existing treatments and lifestyle interventions.

How promising are the latest monoclonal antibodies targeting amyloid-ß for the treatment of early Alzheimer's disease?

INTRODUCTION: Monoclonal antibodies targeting amyloid-ß are the first disease-modifying treatments for Alzheimer disease to have received FDA-approval. There are three different drugs approved or pending FDA-approval: aducanumab, lecanemab, and donanemab. These three drugs are each in different stages of regulatory approval by the FDA. AREAS COVERED: We discuss the development of these drugs, the data regarding their clinical efficacy, their dosing regimens, and side effects. In addition, we examine pragmatic issues with their potential implementation as common treatments to slow the rate of decline in Alzheimer disease, and what unanswered questions remain regarding this new class of drugs. EXPERT OPINION: We conclude that these new monoclonal antibodies that target amyloid-ß represent a genuine advance in the treatment of Alzheimer disease. However, questions remain regarding their clinical significance. Additionally, it is presently unclear which patients would most benefit from these expensive drugs given the risk of side effects and the logistical difficulties concerning administration and the determination of eligibility.

A Multiplex Quantitative Reverse Transcription Polymerase Chain Reaction Assay for the Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pilocytic Astrocytomas.

BACKGROUND AND OBJECTIVE: Genomic duplications and fusion involving BRAF and KIAA1549 that create fusion proteins with constitutive B-RAF kinase activity are a hallmark of pilocytic astrocytomas (PAs). The detection of KIAA1549-BRAF fusion transcripts is of paramount importance to classify these tumors and to identify patients who could benefit from BRAF inhibitors. In a clinical setting, the available material for molecular analysis from these pediatric tumors is often limited to formalin-fixed paraffin-embedded (FFPE) tissue. The aim of the present study was to develop a new method to detect the three most frequent KIAA1549-BRAF fusion transcripts, 15-9, 16-11, and 16-9, where numbers refer to the exons fused together, using a FFPE-compatible multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR). METHODS: We compared performance of the assay to a reference singleplex method on a collection of 46 FFPE PAs. RESULTS: The results showed that both methods are comparable. The multiplex method had an overall 97% sensitivity and 100% specificity compared to the singleplex method, and agreement between the two techniques was almost perfect (Cohen's kappa: 0.97). There was no evidence of a significant difference between the qRT-PCR efficiencies of the multiplex technique and of the singleplex assay for all fusion transcripts and for GAPDH, the latter used as a reference gene. The multiplex method consumed four times less complementary DNA (cDNA), cost less, and required half the hands-on technical time. CONCLUSION: The results show that it could be beneficial to implement the multiplex method in a clinical setting, where samples presenting low quantity of degraded RNA are not unusual.