Influenza remains a major global health challenge, with seasonal epidemics causing 3–5 million severe cases and 290,000–650,000 deaths annually. Existing antiviral agents, while clinically useful, face limitations including narrow spectrum, drug resistance, and multi-dose regimens that compromise patient adherence. Single-dose anti-influenza therapy has emerged as a promising strategy to address these challenges by simplifying treatment and improving compliance. This review systematically summarizes recent advances in three classes of single-dose agents: polymerase acidic (PA) endonuclease inhibitors (baloxavir marboxil, suraxavir marboxil, sebaloxavir marboxil, pixavir marboxil, ADC189), neuraminidase inhibitors (e.g., the long-acting Fc conjugate CD388), and polyclonal antibodies (SAB-176). We discuss their mechanisms of action, clinical trial outcomes, and resistance profiles. The comparative analysis reveals that these three classes are not competitive alternatives but rather address distinct clinical needs: PA inhibitors provide convenient acute-phase oral therapy with rapid symptom relief but face I38T/M resistance mutations; CD388 offers extended protection suitable for seasonal prophylaxis in high-risk populations; and SAB-176 represents a passive immunization strategy for immunocompromised patients. Key challenges remain, particularly the I38T/M resistance shared across PA inhibitors and the need for head-to-head clinical comparisons. Together, these developments mark significant progress toward effective, convenient, and resistance-aware influenza management.
Chronic hepatitis D is associated with substantial clinical and economic burden due to its progressive course and risk of severe liver-related complications. The aim of this study was to quantify the economic burden of chronic hepatitis D (HDV) in Italy from societal perspectives, and to estimate the clinical and economic consequences associated with bulevirtide, peginterferon alfa (PEG-IFN-α), and best supportive care (BSC) in HDV-RNA–positive adults with compensated liver disease. The economic impact of HDV infection was estimated using a cost-of-illness (COI) analysis, while the costs and effects of introducing bulevirtide were estimated using a cost-and-outcomes analysis (COA). The COA compared two scenarios: a clinical practice scenario that includes PEG-IFN-α and BSC, and a scenario that introduces bulevirtide. The analyses were conducted from the societal perspective; therefore, direct and indirect estimated costs were included. The most relevant outcomes were quality adjusted life years (QALYs) and the number of deaths. Both analyses were carried out on a standardised hypothetical cohort of 1000 HDV-RNA–positive adult patients with compensated liver disease, over 10 years. A deterministic sensitivity analysis (DSA) was conducted to assess parameter uncertainty. The COI estimated a 10-year economic burden of €34,939,429.41 for the management and treatment of patients with HDV infection in Italy. The COA estimated a total 10-year reduction in disease-related costs of €2,152,752.76 after the introduction of bulevirtide, an increase of 8.26
As human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) use expands, real-world post-marketing safety evidence remains limited, particularly regarding potential formulation-specific adverse-event patterns across oral and long-acting agents. We aimed to characterise the post-marketing safety profiles of FDA-approved PrEP drugs using the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024. Individual Case Safety Reports (ICSRs) listing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), emtricitabine/tenofovir alafenamide (FTC/TAF) or cabotegravir (CAB) as suspected PrEP drugs were included. Two comparator groups were used: all non-PrEP ICSRs and ICSRs involving non-PrEP HIV drugs. Disproportionality was evaluated at the MedDRA high-level term (HLT) level using reporting odds ratios and 95
Despite substantial agreement between the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on new drug approval in the past decades, a few new drugs for the treatment of some of the most prevalent and severe neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as much rarer neurogenetic disorders, were handled differently by the two regulatory agencies. The possible reasons for the differing behaviors of the FDA and EMA are several and wide-ranging, and they will be examined in this opinion-based analysis. How patients’ perceptions of the complex approaches to drug approval and commercialization may create disappointment and confusion will also be reappraised.
Human African trypanosomiasis (HAT), also known as sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei species. Fexinidazole, an oral treatment for HAT, has shown efficacy in both hemo-lymphatic and meningo-encephalitic stages of the disease. After oral administration, only a small fraction of fexinidazole is eliminated unchanged via the renal route; therefore, hepatic metabolic clearance represents a significant portion of the total clearance of fexinidazole. Consequently, in patients with hepatic impairment (HI), total clearance may be decreased, potentially resulting in overexposure of fexinidazole and could lead to modification of the exposures of its two metabolites. This study aims to evaluate the effect of mild and moderate HI on the pharmacokinetics (PK) of fexinidazole and its active metabolites compared with that in participants with normal hepatic function. This Phase I, multicentric, open-label, non-randomised study included 21 participants divided into three groups: mild HI (n = 7), moderate HI (n = 7) and normal hepatic function (n = 7). Each participant received a single oral dose of 1200 mg fexinidazole under fed conditions. PK parameters, including the maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUCinf) and terminal half-life (t½z), of fexinidazole and its metabolites M1 (sulfoxide metabolite) and M2 (sulfone metabolite) were assessed. Safety and tolerability were evaluated through adverse events, laboratory tests and vital signs. In participants with mild HI, the mean Cmax and AUCinf of fexinidazole, M1 and M2 were similar to or slightly higher (up to 1.40-fold; 90
