Drugs最新文献

Acute pain, defined as short-term pain arising from injury or other noxious stimuli, affects patient outcomes, quality of life, and healthcare costs. Safe, effective treatment of acute pain is essential in preventing increased morbidity, mortality, and the transition to chronic pain. In this review, we explore some of the latest therapeutic agents, formulations, combinations, and administration routes of drugs emerging in clinical practice in the USA for the treatment of acute pain. These agents include VX-548 (Suzetrigine), Cebranopadol, AAT-076, Combogesic intravenous (IV), sublingual ketamine, XG004 (naproxen/pregabalin conjugate), and HTX-011 (Zynrelef). We analyze the pharmacodynamics, pharmacokinetics, development status, and clinical implications of these drugs, emphasizing the importance of finding an agent that provides both a strong safety profile and effective relief from acute pain. Our findings show promise but also highlight the need for further large-scale research to allow these drugs to be utilized in a clinical context for patients experiencing acute pain.

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.

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.

Axatilimab (NIKTIMVO™; axatilimab-csfr), an anti-colony-stimulating Factor 1 Receptor (CSF-1R) humanized IgG4 (κ light chain) monoclonal antibody, is being developed by Incyte Corporation and Syndax Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD) and other indications, including idiopathic pulmonary fibrosis (IPF). In August 2024, axatilimab was approved in the USA for the treatment of cGVHD after failure of at least two prior lines of systemic therapy in adult and paediatric patients weighing at least 40 kg. Axatilimab was added to the NCCN guidelines for cGVHD in August 2024. This article summarizes the development milestones leading to this first approval of axatilimab for the treatment of cGVHD.

Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.

The introduction of tumor necrosis factor inhibitors has led to a paradigm shift in the management of inflammatory bowel disease (IBD). The subsequent introduction of both anti-integrins and cytokine blockers has since expanded the biologic armamentarium. However, immunogenicity, defined as the production of anti-drug antibodies (ADAs) to the prescribed biopharmaceutical, means a significant fraction of patients exposed to biologic agents will experience a secondary loss of response to one or more of the drugs. In clinical settings, immunogenicity may be caused by several factors, both patient related (e.g., underlying chronic disease, systemic immune burden, including previous biologic therapy failure, and [epi]genetic background) and treatment related (e.g., dose and administration regimens, drug physical structure, photostability, temperature, and agitation). Here, we outline these elements in detail to enhance biopharmaceutical delivery and therapy for patients with IBD. Moreover, concurrent immunomodulator medication may reduce the risks of ADA generation, especially when using the chimeric drug infliximab. Summarizing the latest developments and knowledge in the field, this review aims to provide strategies to prevent ADA production and information on managing non-responsiveness or loss of response to biologics. Better understanding of the molecular mechanisms underlying the formation of ADAs and the critical factors influencing the immunogenicity of biopharmaceuticals may lead to improved health outcomes in the IBD community that may benefit both the individual patient and society through lower healthcare expenses.

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.

Efgartigimod (Vyvgart^®; Vyvgart^® Hytrulo) is a neonatal fragment crystallizable receptor (FcRn) antagonist indicated for the treatment of generalised myasthenia gravis (gMG) in adults who are acetylcholine receptor (AChR) antibody positive (Ab+). Efgartigimod is approved for both intravenous (IV) and subcutaneous (SC) use. In a pivotal phase III trial, IV efgartigimod was associated with significant and clinically meaningful improvements in myasthenia gravis symptoms and reductions in disease burden. The beneficial effects of IV efgartigimod were reproducible, durable and maintained over the long term. IV efgartigimod also improved health-related quality of life (HRQOL). In another phase III trial, SC efgartigimod PH20 was noninferior to IV efgartigimod in reducing total immunoglobulin G levels. Clinical improvement with SC efgartigimod PH20 was consistent with that of IV efgartigimod and was reproducible over the long term. Efgartigimod was generally well tolerated; the most common adverse events were headache and infections (with IV efgartigimod) and injection-site reactions (with SC efgartigimod PH20). Although further long-term data are required, IV and SC formulations of efgartigimod provide effective, generally well-tolerated and flexible treatment options for adults with AChR Ab+ gMG.

Vunakizumab (^®) is a subcutaneous (SC) recombinant anti-interleukin (IL)-17A humanized monoclonal IgG1/κ antibody being developed by Suzhou Suncadia Biopharmaceutical Co., Ltd (a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd) for the systemic treatment of autoimmune diseases related to the IL-17 pathway, including psoriasis, ankylosing spondylitis and psoriatic arthritis. In August 2024, vunakizumab was approved in China for the treatment of adult patients with moderate-to-severe plaque psoriasis who are suitable for systemic treatment or phototherapy. This article summarizes the milestones in the development of vunakizumab leading to this first approval for the systemic treatment of moderate-to-severe plaque psoriasis.