The affordability of lecanemab, an amyloid-targeting therapy for Alzheimer's disease: an EADC-EC viewpoint.

Lecanemab, an anti-amyloid antibody with effects on biomarker and clinical endpoints in early Alzheimer's Disease (AD), was granted accelerated approval by the FDA in 2023 and regulatory review in Europe is ongoing. We estimate the population potentially eligible for treatment with lecanemab in the 27 EU countries to 5.4 million individuals. Treatment costs would exceed 133 billion EUR per year if the drug is priced similarly as in the United States, amounting to over half of the total pharmaceutical expenditures in the EU. This pricing would be unsustainable; the ability to pay for high-priced therapies varies substantially across countries. Pricing similarly to what has been announced for the United States may place the drug out of reach for patients in some European countries. Disparities in access to novel amyloid-targeting agents may further deepen the inequalities across Europe in health outcomes. As representatives of the European Alzheimer's Disease Consortium Executive Committee, we call for pricing policies that allow eligible patients across Europe to access important innovations, but also continued investments in research and development. Infrastructure to follow up the usage of new therapies in routine care and new payment models may be needed to address affordability and inequalities in patient access.

Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-ß Levels in Patients with Alzheimer's Disease?

Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-ß (Aß) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aß. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aß species, Aß(X-38), Aß(X-40), and Aß(X-42), with the MSD Aß Triplex assay. The concentration of caffeine was 0.79±1.15 µg/mL in the CSF and 1.20±1.88 µg/mL in the plasma. No correlation was found between caffeine consumption and Aß42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aß42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aß profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.