Background:
People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes.
Objective:
To see how a common INSTI, dolutegravir (DTG), affects how the body uses energy. DTG will be compared with a non-INSTI drug, tenofovir alafenamide (TAF).
Eligibility:
Healthy people aged 18 to 55.
Design:
Participants will be screened. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.
Participants will have 2 inpatient stays at the clinic. Each stay will be for 11 nights, with a 3-week break between.
Both DTG and TAF are gel caps swallowed once per day by mouth. Participants will take 1 drug for 8 days during each stay.
Participants will have tests to see how their body uses energy:
They will spend 23 continuous hours in a special room that measures how much oxygen they breathe in and how much carbon dioxide they breathe out. They will do this a total of 6 times.
They will have a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density.
They will lie on a table. Electrodes will be placed on their hands and feet to measure body fat and lean body mass.
They will stand still on a platform for about 30 seconds. High-resolution laser cameras will scan their bodies.

开始日期2024-06-27

申办/合作机构

National Institute of Allergy & Infectious Diseases

CTR20241665 / RecruitingN/A

江苏艾迪药业股份有限公司的多替拉韦钠片与ViivHealthcare B.V.的多替拉韦钠片（商品名：特威凯）在健康受试者中的单次给药、随机、开放、两周期交叉、空腹及餐后状态下的生物等效性研究

主要研究目的：以江苏艾迪药业股份有限公司的多替拉韦钠片为受试制剂，以Viiv Healthcare B.V.持证的多替拉韦钠片为参比制剂，通过单中心、随机、开放、单次给药、两周期、交叉设计来评价两种制剂空腹及餐后状态下的人体生物等效性。次要研究目的：观察受试制剂和参比制剂在中国健康受试者中的安全性。

开始日期2024-06-09

申办/合作机构

江苏艾迪药业股份有限公司

NCT06281834 / Not yet recruiting临床1期IIT

Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Short-course TB prevention/latent TB infection (LTBI) treatment regimens increase completion rates but have not been adequately studied among children living with HIV. Our prospective, open-label PK study will examine and extend use of weekly rifapentine and isoniazid (3HP) among children receiving dolutegravir. This will address gaps in knowledge by examining two-way PK of short-course LTBI treatment in a vulnerable pediatric population.

开始日期2024-05-01

申办/合作机构

The Brigham & Women's Hospital, Inc.

[+1]

100 项与多替拉韦钠相关的临床结果

登录后查看更多信息

100 项与多替拉韦钠相关的转化医学

登录后查看更多信息

100 项与多替拉韦钠相关的专利（医药）

登录后查看更多信息

2,338

项与多替拉韦钠相关的文献（医药）

2024-04-01·HIV medicine

Status of HIV and comorbidities in refugees with HIV from Ukraine

Article

作者: Ringshausen, Felix C ; Behrens, Georg M N ; Dopfer-Jablonka, Alexandra ; Knuth, Christine ; Witte, Torsten ; Silchmueller, Marc ; Thiele, Thea ; Ahrenstorf, Gerrit ; Joean, Oana ; Slevogt, Hortense

Abstract:

Purpose:

To describe the clinical characteristics of refugees with HIV from Ukraine that seek continuation of medical care in Germany.

Methods:

Fourty‐six refugees with HIV that had left Ukraine between 24 February and 30 December 2022 were examined. Information on patients' history was obtained using a standardized questionnaire for clinical care. Interviews were conducted in Russian during their first clinical presentation.

Results:

Fourty‐six persons (41 females and 5 males) were included and their mean age was 39.6 (±8.4) years. The mean time since HIV diagnosis was 8.0 (median, IQR 7.15) years and 70.3% of participants currently received tenfofovir‐DF, lamividine and dolutegravir. Most refugees had an undetectable HIV viral load and their current mean CD4 T cell count was 702 (SD ± 289) per μL. Serology revealed previous hepatitis B infection in 50.4% without evidence for replication, with undetectable anti‐hepatitis B surface antigen in the remaining refugees. Antibodies against hepatitis C were present in 23 refugees (50%), but only 10 patients had been diagnosed with hepatitis C previously. Five refugees had undergone successful antiviral treatment for hepatitis C. Detectable HCV‐RNA was evident in nine patients (19.6%). Sixteen (38.6%) refugees had a positive tuberculosis (TB) interferon gamma release assay, and four were on TB treatment for previously diagnosed infection. One had been diagnosed with multidrug‐resistant (MDR) TB, two with pre‐extensively drug‐resistant (pre‐XDR) TB and two with XDR TB and were treated with combinations of second‐line and novel agents according to WHO guidelines.

Conclusions:

Based on this preliminary analysis of a not fully representative cohort, refugees with HIV from Ukraine were young, mostly healthy females highly adherent to antiretroviral therapy. The rate of transmittable co‐infections urges early diagnostic evaluation and treatment.

2024-04-01·AIDS research and human retroviruses

Effectiveness, Weight Changes, and Metabolic Outcomes on Switch to Generic Dolutegravir/Lamivudine Among People with HIV in Western India: An Observational Study

Article

作者: Pujari, Sanjay ; Dabhade, Diagamber ; Bele, Vivek ; Joshi, Kedar ; Gaikwad, Sunil ; Panchawagh, Suhrud ; Chitalikar, Abhishek ; Rohekar, Chaitrangi

We assessed the effectiveness and safety of switching to generic dolutegravir/lamivudine (DTG/3TC) among People living with Human Immunodeficiency Virus (PWH) in Western India. In this single-center, retrospective observational study, PWH, who switched to DTG/3TC, were followed for virologic, immunologic, and clinical effectiveness, and safety, including weight changes, hyperglycemia, and dyslipidemia. Multivariate linear mixed-effects models were used to predict average change in weight adjusted for age, sex, duration of previous antiretroviral (ARV) regimens, and baseline weight. From May 2017 to July 2022, out of 434 PWH switched to DTG/3TC, 304 with at least 1 follow-up visit were included. Median [interquartile range (IQR)] age was 54 (IQR 49-61) years and 70.1% were male. Prevalence of baseline comorbidities was 57.9% (hypertension-41.5%, chronic kidney disease-40.9%, and diabetes mellitus-18.8%). Reasons for switch were affordability (47.4%), desire for simplification (41.8%), ARV toxicities (19.1%), and concern about potential toxicities (10.2%). Median (IQR) duration of follow-up on DTG/3TC was 40 (IQR 31-49) weeks. No virologic failure was observed. Rates of virologic suppression [viral load (VL) ≤20 copies/mL or target not detected (TND)] at 12, 24, 48, 72, 96 and 120 weeks were 95.2%, 95.9%, 90%, 100%, 81.3%, and 88.4%, respectively. Only 9 (3%) PWH permanently discontinued DTG/3TC. Predicted adjusted mean weight gain of +3.3 kg was observed at 96 weeks. Switching from tenofovir disoproxil fumarate (TDF)/emtricitabine or lamivudine (XTC)/non-nucleoside reverse transcriptase inhibitor (NNRTI) and duration on DTG/3TC were significantly associated with weight gain. Apart from trend in worsening hyperglycemia (nine PWH with new onset diabetes), no clinically significant change in lipids and estimated glomerular filtration rate (eGFR) was documented. Switching to DTG/3TC is an effective and safe option among virologically suppressed PWH with high comorbidity burden in India. In view of the several advantages of DTG/3TC, it may be considered for potential scale-up in the right population, both in private and public health care settings in India.

2024-04-01·AIDS (London, England)

Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy

Article

作者: Fanshawe, Thomas R ; Samsunder, Natasha ; Sookrajh, Yukteshwar ; Hayward, Gail N ; Dorward, Jienchi ; Butler, Christopher C ; Moodley, Pravikrishnen ; Turner, Philip J ; Lessells, Richard ; Garrett, Nigel ; Govender, Katya ; Drain, Paul K

Objective::

We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia.

Design::

Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART).

Methods::

We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia at least 1000 copies/ml using logistic regression models. In exploratory analyses, we used receiver operating curves (ROCs) to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia.

Results::

Among 124 participants, 68 (54.8%) were women, median age was 39 years [interquartile range (IQR) 34–45] and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV [1000 ng/ml increase, odds ratio (OR) 0.97 95% CI 0.94–0.99, P = 0.005] and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95% CI 0.67–0.86, P < 0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV, P = 0.072; DBS TFV-DP, P = 0.003). Nagelkerke pseudo-R2 for the DBS TFV-DP models was higher for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥1000 copies/ml.

Conclusion::

Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.

153

项与多替拉韦钠相关的新闻（医药）

2024-06-17

·药渡

2024年上半年FDA批准药物或新适应症（上）

来源：药渡撰文：五月编辑：哦呼 FDA在2023年批准了55种新药和34种细胞和基因疗法。本文主要总结了FDA在2024年上半年批准药物或新适应症。 6月10日产品：Ipsen和Genfit的Iqirvo 适应症：原发性胆汁性胆管炎周一，FDA批准了近十年来第一种治疗原发性胆汁性胆管炎（PBC）的新药Iqirvo。PBC是一种罕见的肝病，在美国影响约100,000人，并可能导致肝功能衰竭。 Iqirvo的加速批准是基于发表在《新英格兰医学杂志》上的III期ELATIVE试验的数据。ELATIVE试验表明，与安慰剂联合熊去氧胆酸（UDCA）相比，接受Iqirvo联合UDCA（n=108）治疗的患者达到生化反应的复合主要终点的患者增加了13倍（分别为51%和4%，治疗差异为47%）[1,2]。 6月10日产品：Almirall的Klisyri 适应症：光化性角化病致力于医学皮肤病学的全球制药公司Almirall今天宣布FDA已批准Almirall最近的补充新药申请（sNDA），将Klisyri的使用范围扩大到100 cm2。 Klisyri 是一种微管抑制剂软膏，现已批准以350毫克的包装尺寸进行，是一种为期5天的局部现场治疗，用于治疗面部或头皮的光化性角化病（AK）。该sNDA得到了一项额外的3期、多中心、开放标签、临床安全性研究的支持，该研究涉及美国100多名患者。该研究的主要终点是评估将替巴尼布林应用于成年AK患者面部或秃顶头皮上约100 cm2的视野的安全性和耐受性。该研究显示，对于局部皮肤反应和治疗相关不良事件（AE），结果与在 25cm2区域进行的原始关键试验一致[3]。 6月7日产品：Geron的Rytelo 适应症：骨髓增生异常综合征 Geron Corporation宣布FDA批准其端粒酶抑制剂Rytelo用于骨髓增生异常综合征（MDS）（一组血癌）适应症，受此消息影响，该公司的股价飙升超过30%。Rytelo 专门被批准用于对标准护理治疗红细胞生成刺激剂无反应或不符合条件的输血依赖性贫血MDS患者。该批准是Geron在经营34年后的首次批准，得到了III期IMerge试验数据的支持，其中Rytelo患者在至少24周内的红细胞输注独立性明显高于安慰剂 - 治疗组为28%，安慰剂组为3%。对于那些做出回应的人来说，这种情况中位数持续了1.5年。 6月7日产品：GSK的Arexvy 适应症：呼吸道合胞病毒 6月7日，GSK宣布，FDA批准重组呼吸道合胞病毒（RSV）疫苗Arexvy的适用范围扩大到50-59岁的RSV高危成人。这是首款保护50-59岁高危人群的RSV疫苗。本次扩大适用人群是基于一项III期安慰剂对照、随机研究（NCT05590403）取得的积极结果：50-59岁人群的免疫反应非劣于60岁及以上的人群，达到了主要终点。此外，研究还达到了安全性和免疫原性的二级和三级终点。 5月31日产品：Moderna的mRESVIA 适应症：呼吸道合胞病毒 Moderna公司今天宣布，美国FDA已批准呼吸道合胞病毒（RSV）mRNA疫苗mRESVIA（mRNA-1345）上市，用于保护60岁及以上成年人免受RSV感染引起的下呼吸道疾病（RSV-LRTD），该批准标志着Moderna公司第二项获批的mRNA疫苗。根据新闻稿，mRESVIA是首款以单剂量预充式注射器供应的RSV疫苗。 mRESVIA基于III期ConquerRSV试验获得批准，该试验是一项针对22个国家约37,000名60岁或以上成年人的全球研究，其对RSV下呼吸道疾病的有效率为83.7%。试验中没有发现严重的安全问题。 5月30日产品：BMS的Breyanzi 适应症：套细胞淋巴瘤在本月早些时候获得滤泡性淋巴瘤的批准后，百时美施贵宝的Breyanzi周四获得了FDA对另一个适应症的认可：复发或难治性套细胞淋巴瘤（MCL）。具体而言，Breyanzi 被批准用于既往接受过至少两线全身治疗（包括布鲁顿酪氨酸激酶抑制剂）的MCL患者。该批准得到了TRANSCEND NHL 001的MCL队列结果的支持，其中Breyanzi治疗在目标患者群体中获得了67.6%的完全缓解率。 5月29日产品：Eli Lilly的Retevmo 适应症：RET突变的小儿癌症礼来周三宣布Retevmo获得了加速批准，用于治疗患有RET阳性甲状腺癌和其他携带突变的实体瘤的两岁及以上儿科患者。据Pharmaphorum报道，Retevmo是该类产品中第一种可用于 12 岁以下儿童的药物。 Retevmo此前被授权用于治疗12岁及以上的RET阳性甲状腺癌患者，Retevmo的新批准是基于一项单臂研究，该研究显示总体缓解率为48%，在随访12个月后未达到中位缓解持续时间。 5月29日产品：Tris Pharma的Onyda XR 适应症：注意力缺陷多动障碍周三，Tris Pharma宣布FDA批准了Onyda XR作为第一种用于注意力缺陷多动障碍（ADHD）的非兴奋剂药物，具有液体制剂和夜间给药。 Onyda XR是盐酸可乐定的重新配方，盐酸可乐定于1974年首次被FDA批准用于治疗高血压。可乐定于2010年被批准用于治疗ADHD，品牌名称为 Kapvay，由 Shionogi拥有。 5月29日产品：Teva的Austedo XR 适应症：迟发性运动障碍和亨廷顿舞蹈症 Teva Pharmaceuticals宣布FDA已批准一种新的单粒、每日一次的氘代丁苯那嗪片剂（Austedo XR）给药选择，一种治疗与亨廷顿病（HD）相关的迟发性运动障碍和舞蹈症的药物。氘代丁苯那嗪是一种囊泡单胺转运蛋白2（VMAT2）抑制剂，现在有4种片剂强度（30、36、42 和 48 mg），增加到6 mg、12 mg 和 24 mg 的原始剂量选择。 5月28日产品：Amgen的Bkemv 适应症：阵发性睡眠性血红蛋白尿和非典型溶血性尿毒症综合征今天，FDA批准Bkemv（依库珠单抗-aeeb）作为第一个与Soliris（依库珠单抗）可互换的生物类似药，用于治疗某些罕见疾病。 Bkemv被批准用于以下治疗适应症，这些适应症目前也被批准用于Soliris：治疗阵发性睡眠性血红蛋白尿症（PNH）患者以减少溶血；和治疗非典型溶血性尿毒症综合征（aHUS）患者，以抑制补体介导的血栓性微血管病。 5月16日产品：Amgen的Imdelltra 适应症：小细胞肺癌安进公司周四获得了其首创的双特异性T细胞接合剂Imdelltra的批准，用于治疗广泛期小细胞肺癌（SCLC）。随着FDA的批准，Imdelltra成为第一个用于晚期SCLC的双特异性T细胞接合器疗法。此次加速批准是基于一项针对目标人群中99名患者的II期研究，其中Imdelltra导致40%的总缓解率和9.7个月的中位缓解持续时间。根据美FDA的新闻稿，Imdelltra的标签包含严重或危及生命的细胞因子释放综合征和神经系统毒性的方框警告，包括免疫效应细胞相关神经毒性综合征。 5月1日产品：勃林格殷格翰的Cyltezo 适应症：类风湿性关节炎、克罗恩病、溃疡性结肠炎等周三，FDA批准了勃林格殷格翰的Humira生物仿制药Cyltezo的高浓度和无柠檬酸盐版本，该版本最初于2021年10月获得批准。新批准的剂量为 100 mg/mL，以品牌参考产品的5%折扣出售。 Cyltezo 适用于与Humira相同的所有疾病，包括中度至重度类风湿性关节炎、克罗恩病和溃疡性结肠炎。周三的批准得到了I期伏尔泰-HCLF研究的数据的支持，该研究比较了200名健康志愿者中高浓度和低浓度（50 mg / mL）Cyltezo 制剂的生物利用度。 4月29日产品：辉瑞和Genmab的Tivdak 适应症：宫颈癌 Tivdak最初是由Seagen（已被辉瑞收购）和Genmab合作开发，基于II期innovaTV 204试验中24%的客观缓解率，于2021年9月获得加速批准。近期，FDA将Tivdak的加速批准转化为对化疗后或化疗后进展的复发性或转移性宫颈癌的全面认可。在招募了500多名患者的III期innovaTV 301研究中，与化疗相比，Tivdak显著提高了生存率。2023年10月的一份报告显示，Tivdak可将复发性或转移性宫颈癌患者的死亡风险降低30%；与化疗相比，它还将死亡或疾病恶化的风险降低了33%。没有观察到新的安全信号。 4月29日产品：X4 Pharmaceuticals的Xolremdi 适应症：WHIM综合征周一，FDA批准了X4 Pharmaceuticals的Xolremdi作为WHIM综合征的第一个靶向治疗药物，WHIM综合征是一种非常罕见的免疫缺陷疾病，以其四个特征命名：疣，低丙种球蛋白血症，感染和骨髓细胞增多症。在III期4WHIM试验中，与安慰剂相比，Xolremdi的年化感染率降低了60%；试验受试者每年的感染率低于1例，而安慰剂组为4.5例。随着治疗时间的增加，患者的减少幅度更大。 4月26日产品：辉瑞的Beqvez 适应症：血友病B 近日，FDA批准了辉瑞公司开发的一次性基因疗法Beqvez（fidanacogene elaparvovec），用于治疗18岁或以上中度至重度血友病B成人患者。美国FDA的批准是基于3期临床试验BENEGENE-2的结果。该试验评估了Beqvez在45名中重度血友病B成年男性受试者中的疗效和安全性。根据辉瑞公布的数据，Beqvez使患者的年化出血率降低了71%，年化凝血因子输注率降低了92%。 4月23日产品：Day One Biopharmaceuticals的Ojemda 适应症：小儿低级别胶质瘤周二，Day One宣布FDA已批准第一种用于复发或难治性小儿低级别胶质瘤（pLGG）儿童的药物，该药物具有BRAF融合或重排。据该公司称，这种名为Ojemda的药物也是pLGG唯一允许每周一次治疗方案的全身治疗选择。 4月22日产品：ImmunityBio的Anktiva 适应症：非肌层浸润性膀胱癌周一，FDA批准了ImmunityBio的Anktiva，这是一种用于非肌肉浸润性膀胱癌的同类首创IL-15超级激动剂。Anktiva 将用于卡介苗（BCG）无反应的原位癌患者。它将与卡介苗（BCG）疫苗一起使用，该疫苗传统上用于降低结核病和其他分枝杆菌感染的风险，但长期以来一直被认为可以在膀胱中诱导免疫反应，从而帮助抵抗癌症。 4月18日产品：基因泰克的Alecensa 适应症：非小细胞肺癌周四，FDA批准了基因泰克的Alecensa作为早期间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌患者的首个辅助治疗药物，这些患者已经接受了肿瘤切除术。在一项比较Alecensa辅助治疗与铂类化疗的III期研究中，Alecensa将疾病复发或死亡的风险降低了76%。根据一项探索性分析，患者的中枢神经系统无病生存期也有显着改善。 4月18日产品：武田的Entyvio 适应症：克罗恩病周四，FDA批准了武田Entyvio的皮下（SC）形式，用于静脉注射Entyvio诱导治疗后患有中度至重度活动性克罗恩病（CD）的成人的维持治疗。该批准得到了III期VISIBLE 2研究的支持，该研究显示，与安慰剂组相比，每两周接受108毫克Entyvio SC维持治疗的“具有统计学意义的患者比例”在52周后实现了长期临床缓解；48%的Entyvio患者达到了这一主要终点，而安慰剂对照组的这一比例为34%。 4月11日产品：阿斯利康的Fasnera 适应症：哮喘周四，阿斯利康宣布FDA批准皮下注射IL-5受体阻滞剂Fasnera的扩展适应症，用于6至11岁儿童严重嗜酸性粒细胞性哮喘的附加维持治疗。嗜酸性粒细胞性哮喘是一种严重的形式，是由称为嗜酸性粒细胞的白细胞引起的呼吸系统炎症引起的。据该公司称，Fasnera与人类IL-5受体的α亚基结合，该受体通常在嗜酸性粒细胞和嗜碱性粒细胞的表面表达，触发两种细胞的细胞死亡，同时抑制炎症。 4月8日产品：ViiV Healthcare的Dovato 适应症：HIV ViiV Healthcare的日常HIV片剂Dovato获得了FDA的另一项批准。Dovato将整合酶链转移抑制剂dolutegravir与核苷逆转录酶抑制剂拉米夫定相结合，被批准用于治疗12岁及以上青少年的HIV-1感染，使其成为第一个口服，两种药物，单片方案可用于该患者群体。 4月5日产品：阿斯利康和第一三共的Enhertu 适应症：HER2阳性实体瘤周五，阿斯利康/第一三共宣布Enhertu获FDA加速批准，用于治疗不可切除或转移性HER2阳性（免疫组化[IHC] 3+）实体瘤成年患者，这些患者已接受过先前治疗且缺乏满意的替代治疗选项。该批准得到了II期DESTINY-PanTumor02试验的数据支持，该试验招募了近470名HER2阳性实体瘤患者。中位数为12.75个月后，Enhertu治疗的总体缓解率为37.1%，而缓解持续时间为11.3个月。患者平均存活6.9个月，无疾病进展，总体存活13.4个月。试验参与者患有多种癌症，包括胆道癌、膀胱癌、宫颈癌、胰腺癌和某些罕见肿瘤。 4月5日产品：强生公司和传奇生物的Carvykti 适应症：多发性骨髓瘤强生公司今天宣布FDA已批准Carvykti用于二线治疗复发或难治性多发性骨髓瘤成人患者，Carvykti成为首个也是唯一一个B细胞成熟抗原（BCMA）靶向疗法，被批准用于治疗多发性骨髓瘤患者。此次批准获得了CARTITUDE-4研究的数据支持，在该研究中，Carvykti治疗导致“与两种标准护理方案相比，无进展生存期的无进展生存期具有统计学意义和临床意义的改善”。 4月5日产品：BMS和2seventy Bio的Abecma 适应症：多发性骨髓瘤 BMS和2seventy bio宣布，2024年4月4日，美国食品药品监督管理局（FDA）批准Abecma®（idecabtagene vicleucel;ide-cel）用于治疗既往两种或多种治疗后复发或难治性多发性骨髓瘤成人患者，包括免疫调节剂（IMiD）、蛋白酶体抑制剂（PI）、以及基于KarMMa-3试验结果的抗CD38单克隆抗体。该批准扩大了Abecma的适应症，使其可用于先前两线治疗后暴露于这三类主要治疗（三类暴露）后复发或难治的患者的早期产品线。Abecma作为一次性输注给药，新的推荐剂量范围为300至510 x 106个CAR阳性T细胞。 4月4日产品：Basilea pharmaceutica的Zevtera 适应症：金黄色葡萄球菌血流感染和社区获得性细菌性肺炎 FDA宣布批准Basilea Pharmaceutica公司自研新分子实体药物Zevtera（有效成分：Ceftobiprole Medocaril Sodium）上市。 Zevtera用于治疗金黄色葡萄球菌血流感染（菌血症）（SAB）成人患者（包括右侧感染性心内膜炎患者），急性细菌性皮炎和皮肤结构感染（ABSSSI）成人患者，以及社区获得性细菌性肺炎（CABP）成人和儿童患者（3个月至18岁以下）。 4月2日产品：Vanda Pharmaceuticals的Fanapt 适应症：1型双相情感障碍 Vanda Pharmaceuticals今天宣布，美国FDA已批准其药品Fanapt（iloperidone）片剂用于急性治疗成人1型双相情感障碍（BP-I）相关的躁狂或混合发作。 4月1日产品：阿斯利康的Voydeya 适应症：阵发性睡眠性血红蛋白尿阿斯利康今天宣布其“first-in-class”口服小分子Voydeya获FDA批准，作为标准疗法补体因子C5抑制剂Ultomiris或Soliris的附加疗法，用于治疗阵发性睡眠性血红蛋白尿症（PNH）成人患者的血管外溶血（EVH）状况。此次批准主要基于随机双盲ALPHA关键3期试验的积极结果：Voydeya达到了从基线到第12周血红蛋白变化的主要终点以及所有关键的次要终点，包括避免输血和慢性病治疗功能评估–疲劳（FACIT-Fatigue）评分的变化。以上是FDA在2024年上半年批准的部分药物或新适应症，由于文章篇幅有限，余下内容将在下篇文章中介绍。参考文献 1. FDA Greenlights First Drug in Nearly a Decade for Rare Liver Disease 2. Kowdley. K.V, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185 3. FDA approves Almirall’s Klisyri® (tirbanibulin) for the treatment of actinic keratosis on expanded area of face or scalp up to 100 cm2 专栏作者五月药物化学硕博，国外博士后，现从事药物研发工作，热爱医药行业，愿与各位同行互相学习、进步，共同见证创新药的发展。 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！点击下方“药渡“，关注更多精彩内容 CAR-T疗法：临床现状与应用前景解析剧情反转---AD重磅新药距离获批仅差临门一脚 NK细胞疗法：优势与挑战并存，能否精准施治扬长避短？点击蓝字关注我们

临床3期上市批准疫苗基因疗法

2024-05-13

·BioSpace

Excision’s CRISPR-Based HIV Treatment Fails to Show Curative Potential in Early Study

Pictured: 3D illustration of the CRISPR-Cas9 system editing a stretch of DNA/iStock, Meletios Verras Excision BioTherapeutics’ attempt to use a CRISPR-based gene editing therapy to cure HIV has failed an early-stage study, according to several media reports on Friday. Results from the Phase I trial of five patients showed that Excision’s CRISPR therapeutic did not strongly suppress the HIV virus. Three patients who were taken off of antiretroviral therapy soon developed viral rebound and needed to resume conventional treatments, according to reporting by STAT News. Still, Excision’s approach did show signs of promise. One patient was able to keep the virus at bay for 16 weeks after stopping antiretroviral treatment before rebounding. Typically, HIV levels resurge after around four weeks. The experimental CRISPR treatment also appears to have lowered the number of infected cells in this patient, according to STAT. In response to the disappointing outcome, CEO Daniel Dornbusch told STAT that Excision is “encouraged” by the safety data in the Phase I study, which suggests that “in-vivo CRISPR can be done in a safe way in humans.” The company will use these findings to work on a new gene editing candidate that it can apply to other chronic viral infections, such as herpes and hepatitis B. According to its website, Excision’s lead candidate is EBT-101, a CRISPR-based gene editor that works by cutting out the HIV pro-viral DNA from all infected cells. The candidate is delivered via an AAV9 vector and uses two guide RNAs that can home in on three target sites in the HIV genome, minimizing the likelihood of viral escape. The company is positioning EBT-101 as a potentially curative treatment for chronic HIV and is “rapidly advancing toward clinical trials.” In October 2023, Excision released safety data from its first-in-human Phase I/II study of EBT-101, showing that there were no serious adverse events or dose-limiting toxicities in all three patients that had been dosed with the gene editor at the time. The study found four mild toxicities that could be potentially related to EBT-101, though all were resolved without intervention. The early data also showed that EBT-101 was present at detectable levels in the blood four weeks after treatment. In addition to targeting HIV, Excision is also leveraging its proprietary CRISPR-based gene-editing platform against herpes 1 and 2, for which it is advancing EBT-104, and hepatitis B, for which it is developing EBT-107. Several biotech companies have responded to the HIV crisis, including industry powerhouses Gilead and GSK. Gilead owns the oral antiretroviral pill Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), while GSK and partner ViiV Healthcare market the oral pill Tivicay (dolutegravir) and long-acting injectable Cabenuva (cabotegravir/rilpivirine). While these virus-suppressive treatments are effective, a true cure remains elusive and the field continues to face several substantial challenges. In March 2024, the World Health Organization warned of a growing virus resistance against Tivicay. Meanwhile, gene therapies which have strong curative potential still pose potential safety concerns, particularly unintended edits and off-target effects. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

基因疗法临床1期临床结果siRNA

2024-04-25

·EndPoints

In rare move, Colombia issues compulsory license for HIV medicine in effort to expand access

The Colombian government on Wednesday issued a compulsory license for a commonly used drug to treat HIV, the first time the government there has stepped in to manufacture a drug without the drugmaker’s permission. The compulsory license was issued for dolutegravir, which is manufactured by ViiV Healthcare, an HIV-focused drug company operated by GSK. The license gives Colombia’s ministry of health the authority to manufacture the drug under a system established by a World Trade Organization agreement. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

临床研究

100 项与多替拉韦钠相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10113	多替拉韦钠	J05AX12	DB08930

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
HIV感染	美国	ViiV Healthcare Co.	2013-08-12

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
怀孕	临床3期	南非	ViiV Healthcare Ltd.	2017-03-14
怀孕	临床3期	乌干达	ViiV Healthcare Ltd.	2017-03-14
潜伏性结核	临床2期	美国	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	博茨瓦纳	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	巴西	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	海地	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	马拉维	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	秘鲁	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	南非	ViiV Healthcare Ltd.	2020-08-01
潜伏性结核	临床2期	泰国	ViiV Healthcare Ltd.	2020-08-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03446573 (TANGO, Pubmed)	临床3期	HIV感染	362	Dolutegravir/lamivudine FDC	齋觸製網製廠蓋齋蓋簾(鬱鏇鬱繭構顧觸窪廠壓) = 製鏇鹹遞淵獵壓網糧顧襯艱範糧糧選餘襯觸壓 (觸壓齋鏇築膚簾範構觸 ) 更多	积极	2024-04-08
NCT04857892 (CTgov)	临床1期	HIV感染	41	GSK3640254+DTG (Part 1:Treatment A:GSK3640254 25mg+GSK3640254 100mg+DTG 50 mg)	簾夢築選夢壓鹽夢衊醖(範醖範鑰觸餘壓醖淵衊) = 襯廠積廠壓網膚膚鏇網艱蓋窪餘廠艱齋築願糧 (獵獵願顧範夢艱築鑰蓋, 顧構觸憲夢積構選獵鑰 ~ 顧築蓋衊鏇鹽築齋蓋蓋) 更多	-	2024-03-11
				GSK3640254+DTG (Part 1:Treatment B:GSK3640254/DTG 150/50 mg(Monolayer Tablet))	簾夢築選夢壓鹽夢衊醖(範醖範鑰觸餘壓醖淵衊) = 糧積鹽艱願網餘顧蓋範艱蓋窪餘廠艱齋築願糧 (獵獵願顧範夢艱築鑰蓋, 齋鹹齋夢製顧艱膚網遞 ~ 醖鏇繭糧網艱鹽範鏇淵) 更多
NCT01837277 (CTgov)	临床2/3期	获得性免疫缺陷综合征	186	Dolutegravir 50 mg (Dolutegravir)	餘襯膚鹹窪構憲襯遞齋(艱鬱襯積襯簾艱繭築積) = 齋鑰廠醖鏇獵艱襯鹹鑰鏇廠網遞觸鏇築願構廠 (齋簾獵觸鏇蓋糧鏇齋繭, 製鬱範憲膚網鹹壓鹹艱 ~ 鑰範鹽醖鬱夢蓋選憲鬱) 更多	-	2023-12-14
				Efavirenz-based regimens (Efavirenz)	餘襯膚鹹窪構憲襯遞齋(艱鬱襯積襯簾艱繭築積) = 構餘築壓憲構窪獵範廠鏇廠網遞觸鏇築願構廠 (齋簾獵觸鏇蓋糧鏇齋繭, 鏇醖鹽餘壓構遞遞鹹壓 ~ 鏇築積廠襯鏇構襯鹽淵) 更多
NCT04900038 (CTgov)	临床2期	HIV感染	85	GSK3640254+Dolutegravir (GSK3640254 100 mg + Dolutegravir (DTG) 50 mg)	遞憲觸顧鬱衊鑰築襯壓(構鑰範願夢鬱網鏇鹽餘) = 廠積構築築窪製廠糧壓築鑰鏇鹽鬱鑰製壓積鹽 (鏇鹽鹹簾鑰醖餘鹽選製, 壓醖醖壓窪顧獵憲鹽網 ~ 廠衊蓋窪艱餘顧製醖積) 更多	-	2023-12-14
				GSK3640254+Dolutegravir (GSK3640254 150 mg + DTG 50 mg)	遞憲觸顧鬱衊鑰築襯壓(構鑰範願夢鬱網鏇鹽餘) = 願窪艱獵獵範構觸繭範築鑰鏇鹽鬱鑰製壓積鹽 (鏇鹽鹹簾鑰醖餘鹽選製, 憲蓋壓糧範鏇遞築鏇壓 ~ 齋膚鬱範積衊簾願艱鬱) 更多
NCT03851588 (RADIANT-TB, Pubmed)	临床2期	结核一线 plasma HIV-1 RNA \| CD4 count	108	Tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir	鬱壓範壓繭獵製簾積構(願艱艱膚餘艱廠醖齋簾) = 積窪齋鬱築壓壓積艱夢觸憲艱艱觸構築壓築餘 (願積願衊糧範齋廠膚淵, 70 ~ 92)	积极	2023-07-01
				Tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo	鬱壓範壓繭獵製簾積構(願艱艱膚餘艱廠醖齋簾) = 鏇構廠廠壓觸鬱鹹艱齋觸憲艱艱觸構築壓築餘 (願積願衊糧範齋廠膚淵, 70 ~ 92)
ARTIST (Pubmed)	N/A	二线	62	Tenofovir, lamivudine/emtricitabine, and NNRTI	範觸繭鬱構艱鹽鬱構醖(觸鹹鹽鑰夢遞蓋蓋顧餘) = 膚積製衊願壓遞網繭餘繭蓋獵網範齋網遞繭願 (壓網齋構積襯觸鏇淵壓, 74 ~ 93)	-	2023-01-25
TCTR20210625004 (Pubmed)	临床3期	HIV感染	-	Ritonavir-boosted protease inhibitors	築憲築鹹淵願積築齋構(鹽繭鏇願壓願蓋網淵鏇) = 壓餘糧淵餘鹹觸築鹹範簾餘製壓壓簾簾顧壓艱 (餘築蓋選淵選鑰遞鹹淵, -0.14 ~ 0.48) 更多	-	2022-11-15
				Dolutegravir-based regimen	構簾襯窪夢鹹憲鏇夢鏇(積窪艱齋遞衊顧襯願繭) = 餘製願獵艱觸鏇鑰餘壓艱簾築築鹹積鑰淵遞鹽 (繭夢衊憲艱夢淵醖蓋艱 )
NCT03512964 (CTgov)	N/A	HIV感染	32	Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet [DESCOVY]+Dolutegravir 50 MG	獵觸築鬱顧夢壓糧醖窪(膚齋夢積膚壓壓齋網蓋) = 淵艱憲範廠憲積鬱積繭餘廠顧範積蓋願範膚選 (觸鏇鹽鏇襯夢遞獵壓鹽, 選構襯糧築壓鏇遞構選 ~ 構積廠遞憲願壓憲壓壓) 更多	-	2022-10-27
NEAT-022 (Pubmed)	N/A	HIV感染	-	DTG-I	鑰範構艱壓選鬱製鬱願(選積願醖遞壓夢憲廠憲) = 積鬱觸醖淵鑰窪鹽鏇選簾淵顧鹽繭網觸簾觸積 (繭範鏇簾遞醖鹹鬱艱觸 )	积极	2022-10-19
				DTG-D	鑰範構艱壓選鬱製鬱願(選積願醖遞壓夢憲廠憲) = 鏇鬱範鑰鹽艱夢蓋憲壓簾淵顧鹽繭網觸簾觸積 (繭範鏇簾遞醖鹹鬱艱觸 )
NCT02259127 (ODYSSEY, Pubmed) 人工标引	临床2/3期	HIV感染一线 \| 二线	85	dolutegravir	範遞鹽築齋餘鹽築鏇獵(窪餘鹹鬱觸網鏇鑰鏇網) = 積鹽鏇鹹窪範獵鑰齋遞網網選積構範獵遞範醖 (衊醖衊鏇襯艱鏇構繭廠 ) 更多	积极	2022-09-01
				Standard of care	範遞鹽築齋餘鹽築鏇獵(窪餘鹹鬱觸網鏇鑰鏇網) = 廠範遞夢憲積憲積衊鹹網網選積構範獵遞範醖 (衊醖衊鏇襯艱鏇構繭廠 ) 更多