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Mpox, caused by the monkeypox virus (MPXV), is categorized into two primary clades: Clade I and Clade II, with notable outbreaks linked to Clade IIb. Historically endemic in Africa, recent years have seen significant global spread. The World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern in August 2024, highlighting the emergence of Clade Ib outside Africa and the broadening demographic impact of the outbreak. This review updates the current status of mpox vaccines and treatments, including their safety and effectiveness. There are two US Food and Drug Administration (FDA)-approved vaccines for the prevention of mpox disease, Jynneos^TM and ACAM2000^®. The Jynneos^TM vaccine, recommended for high-risk individuals, has seen limited uptake despite its efficacy in preventing disease. Tecovirimat, while FDA-approved for smallpox and available in the European Union for mpox, has shown mixed results in recent trials, with new data suggesting limited effectiveness in Clade I infections and emergence of new mutations with resistance to this drug. Brincidofovir and Vaccinia Immune Globulin Intravenous offer additional treatment options, particularly for severe cases, although their use is constrained by regulatory and logistical challenges. Furthermore, the WHO recently approved the first commercial molecular assay, the Alinity m MPXV assay by Abbott Molecular Inc., for emergency use-an essential step in expanding testing capacity in regions experiencing mpox outbreaks. These updates underscore the critical need for continued research to enhance therapeutic outcomes and adapt public health strategies. Ensuring equitable access to vaccines, treatments, and diagnostics remains a significant challenge as the global community responds to the evolving mpox situation.

Enlonstobart (Enshuxing^®), a recombinant, fully humanised immunoglobulin G4 monoclonal antibody targeted against programmed cell death protein 1 (PD-1), is being developed by the CSPC Pharmaceutical Group for the treatment of advanced cervical cancer and other solid tumours. Enlonstobart received its first approval (a conditional marketing authorisation) in June 2024, in China, for use in patients with recurrent or metastatic programmed cell death ligand 1 (PD-L1)-positive cervical cancer who have failed previous platinum-containing chemotherapy. Phase III clinical evaluation of enlonstobart for use as first-line treatment (in combination with chemotherapy ± bevacizumab) in patients with recurrent or metastatic PD-L1-positive cervical cancer is also underway in China. Additionally, phase II clinical development of enlonstobart (as a part of combination therapy) for use against a range of other solid tumour types is continuing. This article summarises the milestones in the development of enlonstobart leading to this first approval for recurrent or metastatic cervical cancer.

Fulzerasib (Dupert^®; Innovent Biologics/GenFleet Therapeutics) is an orally active small molecule inhibitor of the KRAS G12C mutant protein being developed for the treatment of solid tumors harboring the KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer. Fulzerasib received its first approval on 21 August 2024 in China, for the treatment of adults with KRAS G12C-mutated advanced NSCLC who have received at least one line of systemic therapy. This conditional approval was based on the positive results of a single-arm, phase II study. This article summarizes the milestones in the development of fulzerasib leading to this first approval for KRAS G12C-mutated advanced NSCLC.

The accelerated approval (AA) pathway was established by the United States Food and Drug Administration (FDA) to provide earlier access to therapies for patients with serious medical conditions and unmet medical needs. Since its inception, the AA pathway has been used for novel treatments across different therapeutic areas, but most prominently in oncology, including the immune checkpoint inhibitor class. This review article describes the history of regulatory approvals for pembrolizumab, an immunotherapy agent targeting programmed death receptor-1 (PD-1), and use of the AA pathway and the corresponding regulatory decisions made by the FDA. From its first AA in September 2014 to February 2024, pembrolizumab has used the accelerated pathway for roughly 40% of the approved indications listed in the US Prescribing Information and was the first oncology therapy to receive an AA for an alternate dosing regimen and a tissue-agnostic indication. As of February 2024, 14 of the 18 indication-specific AAs and 1 post-marketing requirement (PMR) for the alternate dosing regimen AA were converted to traditional approvals. Accelerated approvals for two indications were withdrawn, and the remaining ongoing PMRs are not due until later in 2024 or 2025. The median conversion time from AA to traditional approval was 2.6 years, which is roughly 6 months earlier than the median time reported for oncology AAs. While FDA was the first agency to establish an expedited approval pathway, regulators from other countries have established similar pathways. For pembrolizumab, approximately half of the datasets that supported US AAs also supported expedited approval, or sometimes full approval, in Canada, EU, Australia or Japan. Ultimately, the AA pathway balances the provision of earlier access to therapies with overcoming uncertainty about potential effectiveness, and therefore it is important to confirm treatment benefit and withdraw indications that do not confirm benefit in a timely manner. The regulatory strategy and use of this expedited program for pembrolizumab highlights the importance of the AA pathway in providing oncology patients with earlier access to life-saving medications.

Odronextamab (Ordspono^™), a CD20xCD3 bispecific antibody, is being developed by Regeneron Pharmaceuticals for the treatment of B-cell non-Hodgkin's lymphoma. On 26 August 2024, odronextamab received its first approval in the EU as monotherapy for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) or relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of systemic therapy. Clinical trials in various other B-cell non-Hodgkin's lymphoma, including mantle cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukaemia, are underway in multiple countries. This article summarizes the milestones in the development of odronextamab leading to this first approval for the treatment of adult patients with relapsed/refractory FL or relapsed/refractory DLBCL.

Trientine tetrahydrochloride (TETA-4HCl, Cuvrior^®) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to D-penicillamine (DPA). Trientine hydrochloride capsules are inherently unstable requiring strict cold chain storage conditions from production, transportation, and use at home by the patient. Trientine tetrahydrochloride has a distinctive, patent-protected unique polymorphic form, which permits the production at scale of film-coated scored tablets deemed room temperature stable for 36 months. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamic, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics. Trientine tetrahydrochloride is the only trientine formulation that has been compared with DPA in a prospective randomized clinical trial, demonstrating non-inferiority to DPA in adults with stable Wilson disease. On 28 April, 2022, the US Food and Drug Administration approved TETA-4HCl for use in adult patients with Wilson disease who are de-coppered and tolerant to DPA. Health authorities in multiple countries worldwide have approved TETA-4HCl for the treatment of adults and children aged 5 years or more who are intolerant to DPA including the European Union, UK, Saudi Arabia, Switzerland, Colombia, Australia, New Zealand, and China. This article aims to provide a comprehensive narrative review of the key milestones in the development of TETA-4HCl.

Gram-negative multidrug-resistant (MDR) bacteria, including Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa, pose a significant challenge in clinical practice. Infections caused by metallo-β-lactamase (MBL)-producing Gram-negative organisms, in particular, require careful consideration due to their complexity and varied prevalence, given that the microbiological diagnosis of these pathogens is intricate and compounded by challenges in assessing the efficacy of anti-MBL antimicrobials. We discuss both established and new approaches in the treatment of MBL-producing Gram-negative infections, focusing on 3 strategies: colistin; the recently approved combination of aztreonam with avibactam (or with ceftazidime/avibactam); and cefiderocol. Despite its significant activity against various Gram-negative pathogens, the efficacy of colistin is limited by resistance mechanisms, while nephrotoxicity and acute renal injury call for careful dosing and monitoring in clinical practice. Aztreonam combined with avibactam (or with avibactam/ceftazidime if aztreonam plus avibactam is not available) exhibits potent activity against MBL-producing Gram-negative pathogens. Cefiderocol in monotherapy is effective against a wide range of multidrug-resistant organisms, including MBL producers, and favorable clinical outcomes have been observed in various clinical trials and case series. After examining scientific evidence in the management of infections caused by MBL-producing Gram-negative bacteria, we have developed a comprehensive clinical algorithm to guide therapeutic decision making. We recommend reserving colistin as a last-resort option for MDR Gram-negative infections. Cefiderocol and aztreonam/avibactam represent favorable options against MBL-producing pathogens. In the case of P. aeruginosa with MBL-producing enzymes and with difficult-to-treat resistance, cefiderocol is the preferred option. Further research is needed to optimize treatment strategies and minimize resistance.