Comparative Evaluation of Atraumatic Restorative Treatment (ART), Silver Modified Atraumatic Restorative Technique (SMART) using 38% Silver Diamine Fluoride (SDF) Gel with and without Potassium Iodide (KI) in Carious Primary Molar Teeth using FDI Criteria: A Randomized Clinical Study. - NIL

开始日期2024-08-01

申办/合作机构-

CTRI/2024/01/061296 / Not yet recruiting临床3期IIT

AN IN-VIVO COMPARATIVE EVALUATION OF POTASSIUM IODIDE AND GLUTATHIONE IN REDUCING THE STAINING PROPENSITY OF SILVER DIAMINE FLUORIDE IN PRIMARY ANTERIORS- A RANDOMIZED CONTROL TRIAL

开始日期2024-01-14

申办/合作机构-

CTRI/2023/10/058857 / Recruiting临床4期IIT

Clinical Effectiveness of Silver Modified Atraumatic Restoration with Potassium Iodide Application versus Atraumatic Restorative Treatment for Treating Occlusal Caries in Primary Molars – A Randomized Controlled Study - SMART

开始日期2023-10-30

申办/合作机构

Manipal College of Dental Sciences, Mangalore

100 项与碘化钾相关的临床结果

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100 项与碘化钾相关的转化医学

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100 项与碘化钾相关的专利（医药）

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1,468

项与碘化钾相关的文献（医药）

2024-12-31·Journal of Oral Microbiology

Anticandidal effect of multiple sessions of erythrosine and potassium iodide-mediated photodynamic therapy

Article

作者: Pimha, Surachai ; Saithong, Pattranun ; Pitaksanurat, Pran ; Damrongrungruang, Teerasak ; Sirikarn, Prapatsara ; Mayeah, Nirawat

BackgroundErythrosine+potassium iodide-mediated photodynamic therapy has shown an anticandidal effect. Single session, however, has inadequate fungal inhibition.ObjectivesWe aimed to examine the effects of multiple aPDT sessions on Candida albicans inhibition and singlet oxygen formation.Methods220 μM erythrosine +/-100 mM potassium iodide was applied to C. albicans biofilms for 1 min prior to irradiation at 530±10 nm using a 250 mW/cm² light-emitting diode. Negative and positive controls were phosphate buffer saline and nystatin, respectively. Single, double and triple irradiation sessions with a 5 min resting time between sessions were performed. Post-treatment candidal counts were done at 0, 1 6 and 24 hr while log₁₀ colony forming unit/ml was calculated and compared using a Kruskal-Wallis with Dunn's post hoc test at a p<0.05 - Singlet oxygen amount was compared using one-way ANOVA with a post hoc test at a p< 0.05.ResultsTwo and three irradiation sessions to erythrosine+potassium iodide could inhibit Candida albicans at 7.92 log₁₀CFU/ml (p < 0.001) . Singlet oxygen from a combination groups was significantly higher than for erythrosine (positive control). Moreover, the correlation coefficient (r) between singlet oxygen production and decreased Candida albicans counts was equal to 1.ConclusionMultiple sessions PDT of 220 μM erythrosine+100 mM potassium iodide effectively inhibited a Candida biofilm.

2024-11-01·Journal of Esthetic and Restorative Dentistry

Remineralization efficiency of three different agents on artificially produced enamel lesions: A micro‐CT study

Article

作者: Gürcan, Aliye Tuğçe ; İlisulu, Sabiha Ceren ; Şişmanoğlu, Soner

AbstractObjectiveThis study aimed to assess the remineralization efficacy of casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP), silver diamine fluoride/potassium iodide (SDF/KI), and sodium fluoride with functionalized tricalcium phosphate (NaF/fTCP) on artificial early enamel lesion using laser fluorescence and micro‐CT analysis.MethodologyOn extracted impacted third molars, artificial enamel lesions were prepared. Twenty‐eight specimens were randomly assigned to four groups (n = 7 per group): a control group (artificial saliva), CPP‐ACP (GC Tooth Mousse), SDF/KI (Riva Star), and NaF/fTCP (Clinpro White varnish). Following the manufacturer's instructions, the remineralization agents were applied to demineralized surfaces. Laser fluorescence and micro‐CT were used to evaluate the remineralization efficacy of the agents and analyzes were performed during four stages: before demineralization, after demineralization, 1st day of remineralization and 30th day of remineralization. Shapiro–Wilk test, repeated measures two‐way ANOVA, and Spearman correlation tests were used for statistical analysis. A significant level of p < 0.05 was established.ResultsSDF/KI significantly reduced the lesion area and lesion volume on the demineralized enamel surface after 30 days of remineralization. In the T3 period, SDF/KI increased the mineral density statistically significantly compared to the T1 period. The laser fluorescence values for all three remineralizing agents exhibited a linear decrease. A significant correlation between the fluorescence values and the mineral density was found (p = 0.01).ConclusionAll three investigated agents were showed positive remineralization efficacy on artificial enamel lesion. However, SDF/KI, containing silver diamine fluoride and potassium iodide exhibited superior than other agents in promoting remineralization.Clinical SignificanceAlthough all three remineralization agents showed positive remineralization efficacy on artificial enamel lesions, SDF had higher remineralization performance over the other two agents. SDF has potential to prevent progression of demineralization in treating children with high caries risk in the long‐term.

2024-10-01·Photodiagnosis and Photodynamic Therapy

Clinical aPDT's effect on Candida albicans: Antifungal susceptibility, virulence gene expression, and correlation with leukocyte and neutrophil counts

Article

作者: Du, Meixia ; Xuan, Weijun ; Huang, Liyi ; Hamblin, Michael R

BACKGROUNDOur previous clinical trial demonstrated that antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) and potassium iodide (KI) effectively killed Candida albicans (C. albicans) in adult AIDS patients with oral candidiasis, regardless of biofilm formation or 25S rDNA genotype. This study evaluated changes in antifungal susceptibility and virulence gene expression in C. albicans before and after aPDT, and explored factors related to clinical aPDT efficacy.METHODSTwenty-one adult AIDS patients with C. albicans oral candidiasis were divided into Group a (400 μM MB, N = 11) and Group b (600 μM MB, N = 10). Both groups received two aPDT treatments, where MB was applied for 5 min, followed by 300 mM KI, and illuminated for 30 min (37.29 J/cm²). C. albicans isolates were collected before and after treatment to assess antifungal susceptibility (fluconazole, itraconazole, flucytosine, amphotericin B) and gene expression (CAT1, HWP1). Peripheral blood tests were analyzed for correlations with aPDT efficacy.RESULTSaPDT reduced minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, and flucytosine, with significant reductions primarily after the first treatment. MIC reductions differed between groups, with Group a showing greater decreases in flucytosine and fluconazole MICs, and Group b in amphotericin B MICs. No significant changes in CAT1 or HWP1 expression were observed. Clinical efficacy of aPDT negatively correlated with leukocyte and neutrophil levels.CONCLUSIONSaPDT effectively reduces MICs of antifungal drugs against C. albicans isolated from treated patients, particularly after the first treatment. The concentration of MB required to reduce MICs varies among different antifungal drugs. aPDT does not alter CAT1 or HWP1 expression, and its clinical efficacy in eradicating C. albicans is negatively associated with leukocyte and neutrophil levels.

项与碘化钾相关的新闻（医药）

2024-06-11

·PRNewswire

Global Anti-Radiation Drugs Market to Register Incremental Growth at a CAGR of ~9% by 2030 | DelveInsight

The rise in demand for anti-radiation drugs is mainly driven by several factors. These include the growing occurrence of side effects linked to cancer screening methods, heightened risks of exposure to radiological or nuclear emergencies, and the increasing focus of nuclear-capable nations on safeguarding against radiation. These trends are expected to fuel the expansion of the anti-radiation drugs market from 2024 to 2030. LAS VEGAS, June 11, 2024 /PRNewswire/ -- DelveInsight's Anti-Radiation Drugs Market Insights report provides the current and forecast market analysis, individual leading anti-radiation drugs companies' market shares, challenges, anti-radiation drugs market drivers, barriers, trends, and key market anti-radiation drugs companies in the market. Key Takeaways from the Anti-Radiation Drugs Market Report As per DelveInsight estimates, North America is anticipated to dominate the global anti-radiation drugs market during the forecast period. In the compound type segment of the anti-radiation drugs market, the Potassium iodide sub-category had a significant revenue share in the year 2023. This can be ascribed to the various characteristics and advantages associated with potassium iodide. Notable anti-radiation drugs companies such as Novartis AG, Anbex Inc., Amgen Inc., Myelo Therapeutics, Arco Pharmaceuticals LLC, BTG International Inc., Cellphire Inc., Darnitsa, Enzychem Lifesciences Corporation, Humanetics Corporation, Mission Pharmacal Company, Chrysalis BioTherapeutics Inc., Pluri Inc., Partner Therapeutics, HEYL Chemisch-pharmazeutische Fabrik GmbH & Co. KG., RxBio Inc., Coherus Biosciences, Onconova Therapeutics, Jubilant Life Sciences, Soligenix Inc., and several others, are currently operating in the anti-radiation drugs market. In September 2023, the U.S. Department of Defense awarded Edina-based Humanetics a USD 20 million contract to develop a pill that prevents radiation damage in military members and first responders affected by events such as nuclear accidents, warfare, and dirty bombs. In May 2023, the first-in-human clinical trial of an experimental oral drug for removing radioactive contaminants from inside the body, testing the safety, tolerability, and processing in the body of escalating doses of the investigational drug product HOPO 14-1 was initiated in healthy adults. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, was funding the Phase 1 trial, which was sponsored and conducted by SRI International of Menlo Park, California. In March 2022, Novartis announced that the US Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with a certain type of advanced cancer called prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) that has spread to other parts of the body. These patients have already been treated with other anticancer treatments (androgen receptor pathway inhibition and taxane-based chemotherapy). To read more about the latest highlights related to the anti-radiation drugs market, get a snapshot of the key highlights entailed in the Global Anti-Radiation Drugs Market Report Anti-Radiation Drugs Overview Anti-radiation drugs are pharmaceutical compounds designed to mitigate the damaging effects of radiation exposure on the human body. These drugs work by either scavenging free radicals generated by radiation or by enhancing the repair mechanisms of cells damaged by radiation. One class of anti-radiation drugs includes radioprotectors, which are administered before radiation exposure to prevent or reduce its harmful effects. Another class, known as radiomitigators, is given after exposure to alleviate the severity of radiation-induced damage. These drugs hold significant promise in scenarios such as nuclear accidents, medical radiation therapy, and space travel, where the risk of radiation exposure is a concern. Research into anti-radiation drugs is ongoing, with scientists continually striving to improve their efficacy and minimize side effects. Some compounds under investigation show potential not only in protecting against acute radiation sickness but also in mitigating long-term effects such as cancer development. As our understanding of radiation biology advances, coupled with advancements in drug development technologies, the prospects for more effective and accessible anti-radiation drugs continue to brighten, offering hope for safer environments in radiation-prone situations. Anti-Radiation Drugs Market Insights In 2023, North America dominated the anti-radiation drugs market, primarily due to several factors contributing to growth. These include a substantial patient population afflicted with various illnesses like cancer, increasing numbers of diagnostic procedures, and governmental initiatives aimed at public health in the region. This trend is expected to continue from 2024 to 2030. The prevalence of cancer in the United States, for example, drives a significant demand for anti-radiation drugs. Statistics from the American Cancer Society projected around 2 million new cancer cases in the United States in 2024, leading to heightened demand for these drugs to support cancer diagnostic procedures. Additionally, the US benefits from a strong focus on clinical research and the presence of leading pharmaceutical companies, further bolstering the market for anti-radiation drugs. Moreover, in 2022, the US Department of Health and Human Services (HHS) allocated USD 290 million for the purchase of Nplate, a drug produced by Amgen USA Inc., intended to treat radiation sickness in the event of a nuclear emergency. This investment reflects ongoing efforts to enhance preparedness for radiological and nuclear emergencies and underscores the commitment to saving lives in such scenarios. To know more about why North America is leading the market growth in the anti-radiation drugs market, get a snapshot of the Anti-Radiation Drugs Market Outlook Anti-Radiation Drugs Market Dynamics The market dynamics of anti-radiation drugs are driven by a complex interplay of factors ranging from technological advancements to geopolitical events and regulatory frameworks. One of the primary drivers is the increasing threat of radiation exposure from various sources such as nuclear accidents, medical procedures, and potential radiological terrorism. This heightened awareness has propelled research and development efforts to create effective anti-radiation drugs that can mitigate the harmful effects of radiation exposure. Moreover, the growing prevalence of cancer and the widespread use of radiation therapy as a treatment modality has further fueled the demand for anti-radiation drugs. As more individuals undergo radiation-based treatments, there is a parallel need for medications that can protect healthy tissues and organs from the damaging effects of ionizing radiation. The competitive landscape of the anti-radiation drugs market is characterized by both established pharmaceutical companies and innovative startups vying for market share. Established players often leverage their resources and expertise to develop and commercialize new anti-radiation drugs, while startups focus on disruptive technologies and novel approaches to address unmet needs in radiation protection. Government initiatives and regulatory frameworks also play a crucial role in shaping the market dynamics of anti-radiation drugs. Regulatory agencies set standards for safety, efficacy, and quality assurance, which impact the development, approval, and commercialization of these medications. Additionally, government investments in research and development, as well as funding for procurement and stockpiling of anti-radiation drugs for emergency preparedness, influence market dynamics. Overall, the anti-radiation drugs market is characterized by a dynamic landscape driven by technological innovation, healthcare trends, regulatory factors, and geopolitical considerations. As the threat of radiation exposure continues to evolve, so too will the demand for effective anti-radiation drugs, driving further growth and innovation in this important sector of the pharmaceutical industry. Get a sneak peek at the anti-radiation drugs market dynamics @ Anti-Radiation Drugs Market Dynamics Analysis Anti-Radiation Drugs Market Assessment Anti-Radiation Drugs Market Segmentation Anti-Radiation Drugs Market Segmentation By Compound: Potassium Iodide, Prussian Blue, Diethylenetriamine Pentaacetic Acid, Colony Stimulating Factors, and Others Anti-Radiation Drugs Market Segmentation By Indication: Acute Radiation Syndrome, Cancer Treatment, and Others Anti-Radiation Drugs Market Segmentation By Radiation Type: Ionizing Radiations and Non-Ionizing Radiations Anti-Radiation Drugs Market Segmentation By Distribution Channel: Hospital Pharmacies, Retail Pharmacies, and Others Anti-Radiation Drugs Market Segmentation By Geography: North America, Europe, Asia-Pacific, and Rest of World Porter's Five Forces Analysis, Product Profiles, Case Studies, KOL's Views, Analyst's View Which MedTech key players in the anti-radiation drugs market are set to emerge as the trendsetter explore @ Anti-Radiation Drugs Companies Table of Contents Interested in knowing the anti-radiation drugs market by 2030? Click to get a snapshot of the Anti-Radiation Drugs Market Trends Related Reports Cancer Biomarkers Market Cancer Biomarkers Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key cancer biomarkers companies, including F. Hoffmann-La Roche Ltd., Thermo Fisher Scientific, Inc., QIAGEN N.V., Illumina, Inc., Bio-Rad Laboratories, Inc., Abbott Laboratories, bioMérieux SA, BD, Merck Millipore, Agilent Technologies, Myriad Genetics, Sysmex Corporation, Hologic, Inc., Quest Diagnostics, Centogene N.V., PerkinElmer, Inc., Siemens Healthineers, Exact Sciences, R&D Systems, Inc., BioVision, Inc., among others. Cancer Therapy Market Cancer Therapy Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key cancer therapy companies, including GlaxoSmithKline, Eli Lilly & Company, F. Hoffmann-La Roche Ltd, AbbVie Inc., Amgen Inc, Sanofi, Merck & Co., Inc, Novartis AG, Pfizer Inc, AstraZeneca, Bristol Myers Squibb., Gilead Sciences, Inc., Janssen Global Services, LLC, Elekta AB, Varian Medical Systems, Inc., Accuray Incorporated, Pyrexar Medical, Eckert & Ziegler, IBA, Panacea Medical Technologies Pvt. Ltd., among others. Oncology Drugs Market Oncology Drugs Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key oncology drugs companies, including GlaxoSmithKline, Eli Lilly & Company, F. Hoffmann-La Roche Ltd, AbbVie Inc., Amgen Inc., Sanofi, Merck & Co., Inc, Novartis AG, Pfizer Inc, AstraZeneca, Bristol Myers Squibb., Gilead Sciences, Inc., Janssen Global Services, LLC, BAYER AG., Celldex Therapeutics Inc., Alaunos Therapeutics, Inc., Astellas Pharma Inc., Genentech, Inc., Sandoz International GmbH, BeiGene, among others. Liquid Biopsy in Cancer Diagnostics Market Liquid Biopsy in Cancer Diagnostics Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key liquid biopsy in cancer diagnostics companies, including Myriad Genetics Inc., Exact Sciences Corporation, Biocartis, Sysmex Corporation, Thermo Fisher Scientific Inc, Biocept Inc, Agilent Technologies Inc, MDx Health, Neogenomics Laboratories, F. Hoffman La Roche Ltd, Guardant Health, Bio-Techne, Illumina Inc, QIAGEN, Lucence Health Inc, Personal Gemone Diagnostics Inc, SAGA Diagnostics, Agena Bioscience Inc, The Menarini Group, MiRXES Pte Ltd., among others. About DelveInsight DelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

放射疗法

2024-04-24

·医药魔方

诺华：引领核药赛道的「王者」

Pluvicto是核药赛道近几年当之无愧的“明星产品”。据诺华财报披露，Pluvicto 2023年以260%的增幅实现9.8亿美元销售收入，距离成为10亿美元“重磅炸弹”级别药物仅一步之遥。Pluvicto是目前为止年销售额最高的放射性治疗药物，也是在上市销售的次年便实现了这一壮举。过去几年，在Pluvicto治疗突破及商业化成功的带动下，全球核药赛道发展势头强劲。融资方面，医药魔方MedAlpha®数据库显示，2021-2023年，全球核药赛道累计融资超60亿美元，2023年融资金额较2022年上涨了82%，寒冬之下彰显赛道活力；BD方面，核药赛道大额交易频发，诺华、拜耳、罗氏、礼来等巨头加速布局步伐；市场方面，Pluvicto上市不到两年，销售额直逼10亿美元赋予了核药赛道市场空间最直观的想象力。从2022年3月凭借亮眼数据被FDA率先批准用于治疗PSMA阳性去势抵抗性前列腺癌，到获批上市后商业化表现高歌猛进，Pluvicto的成功进一步加强了诺华“全球核药王者”的地位。而回首诺华的“成王之路”，要从两起关键收购说起。全球核药王者的“成功之路”早在2017年，诺华就以39亿美元的价格收购Advanced Accelerator Applications（AAA），获得了放射性配体药物Lutathera（177Lu-dotatate）和相关技术平台；次年，又斥资21亿美元收购Endocyte，获得Pluvicto（177Lu-PSMA-617）和255AC-PSMA-617的权益。这两起颇具前瞻性且眼光精准的收购让诺华在放射性配体疗法（Radioligand Therapy，RLT）赛道拥有了两款极具竞争力的药物——Lutathera和Pluvicto。其中，Lutathera是全球首款获批上市的RLT药物，开启了放射性药物靶向治疗新时代。与碘化钠、氯化镭等上一代核素药物不同，新一代RLT药物（也被称为RDC）与抗体偶联物（ADC）同属偶联药物，结构相似，一般包含四部分：靶向分子（molecular binder），负责精准识别和结合肿瘤靶点；连接子（linker），负责连接靶向分子和螯合剂，同时改善整体药物分子的药学应用；螯合剂（chelator），负责牢固络合放射性核素；放射性同位素（radioisotope），负责显像或治疗肿瘤。得益于这样的结构以及独特的作用机理，RLT具有多重优势，与ADC相比，RLT无需内化和水解linker的过程；与传统小分子/大分子药物相比，RLT药物治疗机制清晰，不仅能在高效精准治疗的同时降低对其他组织造成的损伤，还能避免耐药性。此外，RLT药物是目前临床实操中唯一能够实现诊疗一体化的药物。Lutathera于2017年9月获EMA首批，用于治疗不可切除或转移性、进展性、分化良好（G1及G2）、生长抑素受体阳性的胃肠胰神经内分泌瘤成人患者，随后于2018年1月获FDA批准上市。全球神经内分泌肿瘤新发病例数已从2017年30.69万人增长到2020年32.29万人，预计到2030年新发病例数将增长至35.16万人，存在巨大的治疗未满足空间。上市首年，Lutathera的销售额就达到了1.67亿美元，次年增长至4.41亿美元，在最新的2023年财报中，Lutathera已实现6.05亿美元的销售额。Pluvicto于2022年3月获FDA批准上市，用于接受雄激素受体途径抑制剂（APRI）和紫杉醇化疗的前列腺特异性膜抗原（PSMA）阳性转移性去势抵抗性前列腺癌（mCRPC）成人患者。Pluvicto的获批基于一项关键性III期临床试验（VISION），结果显示，晚期PSMA阳性mCRPC患者的标准治疗加入Pluvicto，可显著延长影像学无进展生存期（rPFS，8.7 vs 3.4个月）和总生存期（OS，15.3 vs 11.3个月）。Pluvicto的商业化成功来得更加迅猛，首年全球销售额达2.71亿美元，2023年销售额跃升至9.80亿美元，预定“重磅炸弹药物”俱乐部席位。Lutathera和Pluvicto的上市奠定了诺华在核药领域的领导者地位，而诺华在核药赛道的快速进展和可观的销售数据，反过来也带动了全球核药市场的火热，为行业发展注入了强心剂。值得一提的是，诺华仍在积极拓展两款已上市明星产品的临床价值，Lutathera和Pluvicto正在从末线治疗往前线走，探索核药的更大空间。2023年10月，诺华在ESMO年会上公布了Pluvicto治疗既往接受过ARPI且PSMA阳性mCRPC患者的III期PSMAfore研究结果。数据显示，试验达到主要终点，在未经化疗的mCRPC患者中展现出超过两倍的影像学无进展生存获益。针对不良事件的分析显示，177Lu-PSMA-617的安全性更优，3-4级不良事件（33.9% vs. 43.1%）和严重不良事件（20.3% vs. 28.0%）的发生率均低于ARPI组。这些结果有望推动Pluvicto向一线治疗进军。诺华近期也再次更新，PSMAfore研究全人群OS数据结果积极，预计于2024提交新的上市申请。Lutathera同样收获了好消息。2024年1月，诺华在ASCO-GI会议上公布了Lutathera一线治疗胃肠胰神经内分泌瘤（GEP-NETs）III期临床NETTER-2的最新临床数据：主要终点mPFS从8.5个月延长至22.8个月，延长至近3倍，疾病进展或死亡风险降低72%，总响应率ORR高达43%，表明Lutathera一线治疗SSTR阳性、2/3级GEP-NETs的III期临床NETTER-2研究达到了PFS主要终点和ORR关键次要终点。这些积极数据为RLT在癌症领域治疗获益带来了更大的想象空间。Lutathera和Pluvicto的成功让诺华迅速在核药赛道占据高地，同时也更加坚定了诺华在核药赛道进一步开疆辟土的决心。除进一步开发已上市的两款RLT药物外，诺华还有包括177Lu-FAP-2286、177Lu-NeoB、225Ac-PSMA-617在内的多款在研RLT产品177Lu-FAP-2286（AAA614）靶向成纤维细胞激活蛋白（FAP)，目前正在实体瘤中开展I/II期临床研究；177Lu-NeoB1靶向胃泌素释放肽受体（GRPR），目前正在乳腺癌、脑角质瘤及其他实体瘤等适应症中进行I/II期临床研究；225Ac-PSMA-617和Pluvicto一样靶向PSMA，但选用的是杀伤力强、射程短的α核素，在前列腺癌治疗中可以发挥更大的优势，目前正在进行I期临床研究。诺华在研RLT管线在潜力项目177Lu-FAP-2286的首次人体试验（NCT04939610）中，研究人员探索了肽靶向放射性核素疗法（Peptide Targeted Radionuclide Therapy，PTRT）的可行性及初步剂量。11例晚期胰腺癌、乳腺癌、直肠癌、卵巢癌患者经68Ga-FAP-2286或68Ga-FAPI-04 PET/CT确认摄取后，接受177Lu-FAP-2286治疗。结果显示，177Lu-FAP-2286在原发和转移性肿瘤病变中具有高摄取和长时间滞留以及可接受的辐射剂量和治疗副作用，可广泛应用于多种肿瘤。该研究首次为177Lu-FAP-2286在不同类型腺癌PTRT治疗方面的可行性提供了临床证据。内部管线研发持续发力之外，过去几年，诺华在核药赛道的BD战略依然出众，2021年以来，通过多项合作，获得多款RLT候选药物和研发平台。以2023年为例，3月，诺华宣布与Bicycle Therapeutics达成17.5亿美元合作，开发基于双环肽的放射性偶联药物（Bicycle® Radio-Conjugates）；4月，诺华又与3B Pharmaceuticals达成4.65亿美元合作，获得其FAP靶向肽技术（包括FAP-2286）治疗和成像应用的全球权益。不难看出，在BD方面的不断深入，是诺华应对当前核药赛道激烈竞争，巩固其核药赛道领导者地位的关键策略。诺华在核药领域的代表性合作并购此外，由于放射性同位素的半衰期较短，核药的商业化放量一直受到产能桎梏。诺华的Pluvicto有效期从工厂包装好开始计时只有5天；Lutathera更短，只有3天，这让全球分散建厂成为刚需。诺华目前已陆续在意大利、西班牙和美国分别设立了放射性药物生产基地，以满足全球患者需求。今年1月，FDA已批准诺华在印第安纳波利斯的生产基地进行Pluvicto的商业化生产。这座7万平方英尺的工厂是诺华最大且最先进的核药生产基地，位于美国中心，毗邻Fedex（联邦快递），12小时即可触达全美病人，能最大限度地为患者和治疗中心提供服务。为了能给医疗卫生机构、医生及患者提供更优质的服务，诺华还独立出品了一系列包括医疗卫生系统建设、药物预定、物流追踪、RLT技术支持、医学教育培训在内的全方位客户服务系统和产品，致力于为医患提供全方位的服务。诺华对RLT的决心，可见一斑。从产品，到管线、产能、商业化，毫无疑问，诺华已经将RLT变成了自己的主场。在JP Morgen2024大会上，CEO Vas Narasimhan对诺华在RLT领域的布局表现出十足的底气，他表示：“放射性配体疗法有望成为诺华建立长期领导力的赛道。”从深耕中国，到建立核药帝国放射性药物产业在中国已成为国家重点支持的战略性新兴产业。近几年，国内陆续出台了《医用同位素中长期发展规划（2021-2035年）》、《放射性体内治疗药物临床评价技术指导原则》、《国家药监局关于改革完善放射性药品审评审批管理体系的意见》等利好政策，助力核药产业发展。其中，2023年4月发布的《国家药监局关于改革完善放射性药品审评审批管理体系的意见》指出，鼓励以临床价值为导向的放射性药品创新，鼓励境外已上市原研放射性药品在我国境内进口注册，并提出将对临床急需的放射性药品上市许可申请给予优先审评审批。诺华的中文名取意“承诺中华”，即通过不断创新的产品和服务，提高中国人民的健康水平和生活质量。作为开发RLT的先驱和领导者，为满足中国患者需求，过去几年诺华进行了多元化布局。为推动Pluvicto在中国获批上市，诺华已在国内开展多项临床试验。其中，针对转移性激素敏感性前列腺癌的一项III期研究（CTR2022147）及针对PSMA阳性转移性去势抵抗性前列腺癌的一项II期研究（CTR20230317）均已完成患者招募。此外，2023年12月，诺华宣布在浙江海盐投资设立一家全新的放射性药物生产基地，以加快将创新型RLT药物引入中国的步伐，造福有临床需求的国内肿瘤患者。该基地的投资总额预计将超过6亿元人民币，将在2026年底投入生产。临床及生产的双重好消息预示着Pluvicto将加速进入中国。除了推进产品获批、商业化，2024年4月21-22日，由中国同位素与辐射行业协会主办的2024年放射性药物创新发展大会暨中国同位素与辐射行业协会放射性药物分会第一届理事会第一次会议宣布，诺华正式成为放射性药物分会副会长单位。此前，该协会会员单位均为国内公司，诺华作为跨国药企的首次加入，既体现了中国核药产业发展的开放性，也体现了诺华与中国核药产业进一步融合的决心。此前，在2024年中国发展高层论坛（CDF）上，诺华CEO Vas Narasimhan也强调了公司在RLT赛道的领先地位，并就加快RLT这一先进疗法的开发与应用积极建言，同时分享了诺华的洞察与实践。诺华在RLT领域的丰富积淀及经验将为中国核药产业发展注入新势能。明星产品、潜力管线的加持，以及生产、运输、医患服务等资源的建置与支持，让诺华登上了全球核药赛道之巅。紧跟中国核药产业发展大势，深度布局中国这一关键市场无疑是诺华志在将RLT打成公司新王牌产业的关键策略。诺华在RLT领域的战略决心与持续布局，正助力其逐步建立“核药帝国”，进一步延续、加强其核药全球王者地位；同时，也将推动全球核药产业迎来新的里程碑，书写新的篇章。注：文章素材来自公开资料Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

并购抗体药物偶联物财报放射疗法上市批准

2024-03-25

·梅斯医学

50%中国人患有甲状腺疾病！《柳叶刀》：3大治疗策略新进展

甲状腺疾病全球流行病学情况与人口碘摄入情况密切相关。根据《中国老年人甲状腺疾病诊疗专家共识（2021）》，中国甲状腺疾病总体患病率为50.96%。在碘充足地区，甲状腺功能亢进症（甲亢）和亚临床甲亢各影响约5%的人口，以毒性弥漫性甲状腺肿（Grave's病）多见；在碘缺乏地区，甲亢患病率较高，甲亢和亚临床甲亢的患病率可高达10%~15%，毒性结节性甲状腺肿比Grave’s病更多见，若采取有效措施纠正碘缺乏，则甲亢发病率呈现出短期内增加，而后逐渐降低至与碘充足地区类似的水平。近日，《柳叶刀》（The Lancet）发表一项研讨会内容，阐述了甲状腺疾病的病因、临床表现、并发症、诊断、治疗策略和未来研究重点方向，以期为临床预防和治疗甲状腺疾病提供参考。截图来源：The Lancet常见3大甲状腺疾病甲状腺毒症指各种原因导致的循环中甲状腺激素过量，引起以神经、循环、消化等系统兴奋性增高和代谢亢进为主要表现的一系列临床综合征，根据是否有甲亢，可分为甲亢性甲状腺毒症和非甲亢性甲状腺毒症。甲亢是甲状腺毒症的病因之一，是甲状腺自主持续性合成和分泌甲状腺激素增多而引起的甲状腺毒症，以Grave’s病最为常见，约占甲亢所有类型的80%。尽管甲状腺毒症和甲亢的术语经常互换使用，不同病因引起的甲状腺毒症患者临床表现相似，但治疗方案和预后不同，在临床上需要仔细鉴别甲状腺毒症的病因。临床实践中，Grave’s病、毒性结节性甲状腺肿和甲状腺炎是尤为常见的疾病类型，相比之下，其他原因（如卵巢甲状腺肿）引起的甲状腺毒症较为罕见。哪些表现可能是甲状腺疾病？由于甲亢病因并不完全明确，不同患者之间的症状表现差异较大。年龄可能是影响因素之一，通常老年人很少出现甲亢相关症状，尽管如此，对于以不明原因体重减轻、房颤或房扑、心悸、情绪改变和其他非特异性表现的主诉的老年人，仍然应提高疑似甲亢的临床判断。Grave’s病患者最常见的症状为甲状腺眼病，也称为“Grave’s眼病”或“眼眶病”，患病率约为25%~40%，而甲状腺皮肤病（胫前粘液水肿）、甲状腺肢端病（杵状指）和其他自身免疫性疾病，如脾肿大、胸腺肿大、脱发、白癜风、恶性贫血和荨麻疹等则较少见。甲亢患者病情严重时可能出现甲亢危象，可伴有一个或多个器官失代偿，发病率约为0.2%，60岁以上人群甲亢危象死亡率高达10%~17%。甲亢危象患者多表现为发热、精神状态改变、胃肠功能紊乱、心动过速伴心律失常和心衰，通常同时伴有急症，如感染、手术或分娩，几乎很少有患者在患病初期就出现甲亢危象。甲状腺疾病的临床指标有何变化？甲状腺毒症的特征为：游离甲状腺素（FT4）和总三碘甲状腺原氨酸（TT3）或游离三碘甲状腺原氨酸（FT3）浓度升高，血清促甲状腺激素（TSH）水平降低，通常低于0.01 mU/L。部分患者可能患有T3甲状腺毒症（FT4浓度在正常范围，但T3浓度增高），多见于病情较轻或早期患者。亚临床甲亢患者甲状腺激素水平在正常范围，但TSH水平异常。对于疑似Grave’s病的患者，特别是患者无典型Grave’s眼病或其他临床症状时，促甲状腺激素受体抗体（TRAb）是关键诊断指标。对于甲状腺毒症病因不明的患者，甲状腺造影和放射性同位素有助于明确病因，通常Grave’s病患者放射性同位素摄碘率升高或升高至正常，而甲状腺炎患者的放射性同位素摄碘率通常非常低或不存在。对于毒性甲状腺结节性甲状腺肿患者，甲状腺造影可以显示甲亢和甲减区域，即“热结节”和“冷结节”。甲状腺超声适用于确定在体格检查或扫描发现的甲状腺结节。甲状腺疾病的三大治疗策略β-受体阻滞剂可缓解甲亢症状。非选择性β-受体阻滞剂——普萘洛尔可长期使用，更长效的β1-受体阻滞剂，如阿替洛尔和美托洛尔也同样有效。甲状腺毒症伴甲亢首选治疗方式取决于潜在的病理生理机制，常用的治疗策略有：抗甲状腺药物、放射性碘治疗和甲状腺切除术。这三种治疗策略对Grave’s病同样有效，但抗甲状腺治疗药物更可能是患者首选治疗方式。对于毒性腺瘤或多结节性甲状腺肿的患者，放射性碘治疗和手术是首选方案。抗甲状腺药物硫氨酰胺类抗甲状腺药物包括：丙基硫氧嘧啶（PTU）、卡比马唑及其代谢产物甲巯咪唑。根据美国和欧洲指南的建议：对于新诊断为Grave’s甲亢的患者，可选用卡比马唑和甲巯咪唑治疗12~18个月，直到TSH水平恢复正常且TRAb为阴性，方可停药。若治疗期间患者TRAb水平持续升高或停药后复发，则可考虑选择卡比马唑和甲巯咪唑继续治疗12个月或更长时间，亦或是选择放射性碘治疗、甲状腺切除术等方式。抗甲状腺药物也有缺点，主要是单疗程治疗后复发率较高（约50%），特别是停药后的前6个月。不过，一项针对128例复发性Grave’s病的纵向研究显示，超过75%的患者在接受了抗甲状腺药物第二疗程治疗后，可达到长期缓解。此外，有证据表明，长期（5~10年）甚至终身使用低剂量的卡比马唑和甲巯咪唑是安全有效的。抗甲状腺药物的初始剂量取决于甲亢严重程度和甲状腺大小。初步控制住病情大约需要1~3个月，而后可将抗甲状腺药物剂量控制在维持正常甲状腺功能所需最低剂量。若病情难以被控制，可以考虑采用阻断和替代治疗方案，即用大剂量抗甲状腺药物完全阻断甲状腺功能，并使用左旋甲状腺素，以避免发生甲减。治疗4~6周后应开始检测甲状腺功能，避免过度治疗引起甲减，特别是Grave’s病，因为患者可能出现严重的甲状腺眼病。若患者达到生化甲状腺功能正常，随访间隔可延长至2~4个月。安全性方面，约有5%的患者可能出现轻微不适反应，包括瘙痒和胃肠道不适。抗甲状腺药物严重副作用比较罕见，仅有不到0.5%的患者可能出现粒细胞缺乏症，通常在治疗3个月发生，表现为发热、咽喉痛或二者兼有，若出现相关症状，且经临床医生证实为粒细胞缺乏症，则需永久停用抗甲状腺药物。放射性碘治疗放射性碘治疗是毒性腺瘤和毒性多结节性甲状腺肿的一线治疗方式，特别是患有合并症的老年患者，因为他们手术的风险很高。放射性碘治疗后第一周，T4和T3的浓度可能会短暂升高，不过Grave’s病中50%~85%的患者最终会进入甲减。此外，大约有10%的甲亢患者在采用放射性碘治疗后，仍无法缓解甲亢症状。放射性碘治疗可以作为一种明确的治疗选择，但并不能达到“立竿见影”的治疗效果，部分多结节甲状腺肿的体积可缩小60%，当然这也要看初始治疗时甲状腺的大小情况。一般来说，在开始放射性碘治疗前需要使用卡比马唑、甲巯咪唑或β受体阻滞剂，以控制甲亢并降低治疗后症状加重的风险，特别是老年患者和重度甲亢患者，通常在治疗前3~7天停药，然后在治疗后3~7天重新开始用药，一直到甲状腺功能正常。安全性方面，放射性碘治疗可能引起颈部压痛、已有甲状腺眼病病情进展或恶化，特别是吸烟人群。因此，放射性碘治疗禁用于伴有重度眼眶病变的Grave’s病患者，若是轻度眼眶病变或临床医生判定存在新发眼眶病变风险的患者（如吸烟、重度甲亢患者等），在接受放射性碘治疗之前，建议使用糖皮质激素进行预防。此外，放射性碘治疗的禁忌证还包括：怀孕（或计划未来6个月怀孕）、母乳喂养和无法遵守辐射安全预防措施人群。最后，尽管有部分研究认为，放射性碘治疗固定剂量和灵活剂量方案对癌症发病率和死亡率影响不存在差异，但也有证据表明，放射性碘治疗与实体瘤的死亡率之间存在剂量依赖性正相关，不过，相关研究结果仍存争议。甲状腺切除术甲状腺切除术可被视为毒性结节性甲状腺肿的一线治疗方案，以及Grave’s病的确定性治疗方案，特别是当其他治疗方案无效、患者无法耐受或存在治疗禁忌证、（疑似）恶性结节、大的甲状腺肿或并发原发性甲旁亢，或是甲状腺切除术为患者首选治疗方式时。对于Grave’s病，甲状腺全切术比甲状腺次全切除术效果更好，并发症情况类似，因此全切是首选。术前患者需要使用抗甲状腺药物，以使甲状腺功能正常；根据临床实践指南的推荐，术中可使用卢戈碘或碘化钾做预处理，以减少患者术中出血；术后患者还需使用左旋甲状腺素治疗。对于毒性结节性甲状腺肿，根据甲状腺结节的数量和分布情况，部分甲状腺切除术或甲状腺全切术都可能是合适的，且术后出现并发症几率较低（1%~2%），特别是主刀医生具有丰富的手术操作经验时（年手术次数＞25~50次）。术后可能出现的并发症包括：术后出血、甲状旁腺功能减退引起的低钙血症（通常为暂时性）和喉返神经损伤，发生概率均在1%左右。此外，还有些特殊类型的甲状腺疾病，如亚临床甲亢、妊娠甲亢等，本文不一一阐述。甲状腺疾病治疗的未来展望在过去的80年里，Grave’s病的治疗选择几乎没有发生过变化。尽管在治疗操作和安全性方面已取得了长足的进步，但现有的治疗方式仍较为有限，特别是停用抗甲状腺药物后，患者疾病复发率较高；以及放射性碘治疗或手术治疗后出现的甲状腺功能减退的问题。过去的10年里，关于Grave’s病的潜在治疗方法的不同作用机制已得到部分验证，不过这些临床研究规模较小，多为开放标签的1期和2期试验，仍有待更多的大型随机对照研究来佐证这些有希望的初步研究结果。达到并维持甲状腺功能正常，或是诱导和治疗甲状腺功能减退似乎有望改变甲亢死亡率高的问题。特别是使用放射性碘诱导甲减，随后采用T4替代疗法，或可降低心血管疾病和总死亡风险。但临床实践中，使用抗甲状腺药物让甲状腺功能维持正常，也不一定能降低死亡风险，这可能是因为患者在接受药物治疗时，甲状腺功能并不总是正常，且在停止药物治疗后还可能复发。目前，长期低剂量抗甲状腺药物治疗对心血管和总死亡的影响尚不明确，但或许是控制甲亢和避免复发的可行性策略，可能优于短期或重复治疗，且似乎对Grave’s病和结节性甲状腺肿同样有效。考虑到即将推出的新型免疫调节和其他靶向药，长期低剂量抗甲状腺药物或将成为治疗Grave’s病的有力选择之一，让我们共同期待这些治疗方式在未来的应用情况。对于部分自主良性甲状腺结节的患者，射频消融术或可作为替代治疗方案。此外，很多患者关心膳食补充剂（如维生素D、硒和Ω-3脂肪酸）是否可预防或治疗Grave’s病，从现有证据来看，虽然有部分研究探索了几种膳食补充剂的作用，但不同研究之间的数据存在相互矛盾的问题。最后，老年群体更容易罹患亚临床甲亢，而非甲亢。考虑纳入观察性研究的荟萃分析结果显示，亚临床甲亢患者更容易发生髋部和其他部位骨折、骨质疏松、心血管事件和死亡风险增加等问题，现有临床指南建议：对于血清TSH浓度低于0.1 mU/L的亚临床甲亢患者，无论是否有症状，都建议采取相关治疗措施（特别是老年患者）。不过，需要指出的是，尽管业内对于轻度亚临床甲亢的治疗尚未形成共识，但短期内开展相关临床对照试验以进一步了解和解决这一问题的可能性也较低。参考资料[1] Chaker L, Cooper DS, Walsh JP, Peeters RP. Hyperthyroidism. Lancet. 2024 Feb 24;403(10428):768-780. doi: 10.1016/S0140-6736(23)02016-0. Epub 2024 Jan 23. PMID: 38278171.[2]中华医学会老年医学分会老年内分泌代谢疾病学组,中华医学会内分泌学分会甲状腺学组.中国老年人甲状腺疾病诊疗专家共识(2021)[J].中华内分泌代谢杂志, 2021, 37(5):20.DOI:10.3760/cma.j.cn311282-20210502-00273.撰文 | 阿拉斯加宝编辑 | 阿拉斯加宝● 必须要重视了!!同一医院先后两名医学生自杀，一个月内三起！这些规培实习生为何如此绝望？如何避免悲剧再次发生？要警惕“维特效应”● Science重磅：长出头发和皮肤修复，都离不开这种常见的维生素！● “神药”减肥的机制明确了！连发两篇Nature，二甲双胍抑制食欲，竟与运动殊途同归？版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」立刻下载梅斯医学APP！

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