A Phase 1b, Multicenter, Open-Label, Parallel-Group, Maximal Use Systemic Exposure (MUSE) Study to Evaluate the Pharmacokinetics, Safety and Tolerability of S6G5T-3 Compared to Retin-A® 0.1% in Subjects With Moderate to Severe Acne Vulgaris

To assess the degree of systemic exposure of S6G5T-3 compared to the Reference Listed Drug (RLD) Retin-A® 0.1% Cream when applied topically once daily for 14 days, under maximal use conditions in adolescents ≥12 years of age and adults with acne vulgaris.

开始日期2019-06-27

申办/合作机构

Sol-Gel Technologies Ltd.

NCT03761784

/ Completed临床3期

A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled Study of S6G5T-3 in the Treatment of Acne Vulgaris

To assess the efficacy of S6G5T-3 compared to its Vehicle when applied once daily for 12 weeks in participants with acne vulgaris.

开始日期2018-12-21

申办/合作机构

Sol-Gel Technologies Ltd.

NCT03761810

/ Completed临床3期

A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled Study of S6G5T-3 in the Treatment of Acne Vulgaris

To assess the efficacy of S6G5T-3 compared to its vehicle when applied once daily for 12 weeks in participants with acne vulgaris.

开始日期2018-12-14

申办/合作机构

Sol-Gel Technologies Ltd.

100 项与过氧苯甲酰/维A酸相关的临床结果

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100 项与过氧苯甲酰/维A酸相关的转化医学

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100 项与过氧苯甲酰/维A酸相关的专利（医药）

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项与过氧苯甲酰/维A酸相关的文献（医药）

2023-09-01·ANNALS OF PHARMACOTHERAPY

Tretinoin 0.1% and Benzoyl Peroxide 3% Cream for the Treatment of Facial Acne Vulgaris

Review

作者: Feldman, Steven R. ; Kontzias, Christina ; Zaino, Mallory

Objective::

To assess the efficacy, safety, and clinical application of tretinoin 0.1%-benzoyl peroxide 3% cream for the topical treatment of acne vulgaris.

Data Sources::

A systematic review of the literature was performed using the terms Twyneo OR tretinoin and benzoyl peroxide OR S6G5T-3 in MEDLINE (PubMed) and EMBASE. ClinicalTrials.gov was searched to obtain completed clinical trial results not published elsewhere.

Study Selection and Data Extraction::

All human studies published in English prior to November 2022 related to pharmacology, clinical trials, safety, and efficacy were evaluated for inclusion.

Data Synthesis::

In two 12-week, phase 3, randomized, vehicle-controlled clinical trials, tretinoin 0.1%-benzoyl peroxide 3% cream significantly reduced inflammatory and noninflammatory facial acne lesions and significantly improved Investigator Global Assessment (IGA) rating to clear or almost clear. The cream has a suitable safety profile, with application site pain and dryness as the most common adverse events.

Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents::

Tretinoin-BPO had similar IGA success compared to other topical retinoid and retinoid-BPO treatments for acne vulgaris. Compared to individual tretinoin and benzoyl peroxide therapy, the combination product streamlines application, which will improve medication adherence; however, the cost of tretinoin-BPO cream may be prohibitive.

Conclusions::

Tretinoin 0.1%-benzoyl peroxide 3% cream is safe and effective for the treatment of moderate-to-severe acne. Long-term trial data on efficacy and tolerability are not yet available.

2021-02-01·CLINICAL CANCER RESEARCH

The Changing Landscape of Therapeutic Cancer Vaccines—Novel Platforms and Neoantigen Identification

Review

作者: Jou, Jessica ; Zocca, Mai-Britt ; Harrington, Kevin J. ; Cohen, Ezra E.W. ; Ehrnrooth, Eva

Abstract:

Therapeutic cancer vaccines, an exciting development in cancer immunotherapy, share the goal of creating and amplifying tumor-specific T-cell responses, but significant obstacles still remain to their success. Here, we briefly outline the principles underlying cancer vaccine therapy with a focus on novel vaccine platforms and antigens, underscoring the renewed optimism. Numerous strategies have been investigated to overcome immunosuppressive mechanisms of the tumor microenvironment (TME) and counteract tumor escape, including improving antigen selection, refining delivery platforms, and use of combination therapies. Several new cancer vaccine platforms and antigen targets are under development. In an effort to amplify tumor-specific T-cell responses, a heterologous prime-boost antigen delivery strategy is increasingly used for virus-based vaccines. Viruses have also been engineered to express targeted antigens and immunomodulatory molecules simultaneously, to favorably modify the TME. Nanoparticle systems have shown promise as delivery vectors for cancer vaccines in preclinical research. T-win is another platform targeting both tumor cells and the TME, using peptide-based vaccines that engage and activate T cells to target immunoregulatory molecules expressed on immunosuppressive and malignant cells. With the availability of next-generation sequencing, algorithms for neoantigen selection are emerging, and several bioinformatic platforms are available to select therapeutically relevant neoantigen targets for developing personalized therapies. However, more research is needed before the use of neoepitope prediction and personalized immunotherapy becomes commonplace. Taken together, the field of therapeutic cancer vaccines is fast evolving, with the promise of potential synergy with existing immunotherapies for long-term cancer treatment.

2020-01-01·Skinmed

Microencapsulated Benzoyl Peroxide and Tretinoin for the Treatment of Acne Vulgaris: Results from a Phase 2 Multicenter, Double-Blind, Randomized, Vehicle-Controlled Study.

Article

作者: Sugarman, Jeffrey ; Webster, Guy F ; Levy-Hacham, Ofra ; Toledano, Ofer

This phase 2, 12-week, multicenter, randomized, double-blind, active- and vehicle-controlled (VC), parallel-group trial assessed the efficacy and safety of silica encapsulated benzoyl peroxide BP (E-BP), two concentrations of silica encapsulated tretinoin (E-ATRA) and their combinations (TWIN high and low) vs VC in 726 males and females ≥9 years of age with moderate-to-severe inflammatory facial acne. The co-primary efficacy endpoints were Investigators Global Assessment (IGA) success rate ("clear" or "almost clear") and changes from baseline in inflammatory and non-inflammatory lesion counts. TWIN high and low were each significantly superior vs VC for IGA success at 12 weeks (39.7% and 27.4%, respectively, vs 12.3%, P < 0.001 and P < 0.01). TWIN high and low resulted in mean reductions in inflammatory lesions of -16.9 (64%) and -17.0 (60.8%) vs -11.5 (42%) for VC. Reductions in non-inflammatory lesions were -23.7 for TWIN low (54.9%) and -23.6 for TWIN high (53.3%) vs -13.7 (32.4%) for VC (all P < 0.001 vs VC). Results for TWIN were also numerically superior to E-BP and E-ATRA. All treatments were safe with comparable skin tolerability. The significant superiority of both combinations over VC and numerical superiority over E-BP and E-ATRA were achieved without an increase in adverse events or reduced skin tolerability.

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项与过氧苯甲酰/维A酸相关的新闻（医药）

2026-01-09

·优麦医生服务号

痤疮诊疗十年：临床医生需要关注的要点

前言寻常痤疮（acne vulgaris）是一种累及毛囊皮脂腺单位的慢性炎症性皮肤病，是全球最常见的皮肤疾病之一。全球总体患病率约为9.4% 1，在青少年群体中高达80%–90%2。虽然痤疮常见于青春期，但并非青少年专属，近年来成人痤疮的发病率逐渐增加，尤其女性患者受到激素水平波动、妊娠和多囊卵巢综合征等因素影响，25岁以上女性的发病率可达12%–22%，而男性约为3%–5%3,4 。在中国，流行病学调查显示总体患病率约为8.1%5，基于多中心社区研究，青少年高峰年龄段的患病率接近一半6。全球疾病负担研究（GBD 2021）提示，1990年至2021年间，青少年痤疮新发病例数由每 10 万人口 8563.4 例上升至每 10 万人口 9790.5 例，痤疮的公共健康负担不断加重 7。痤疮虽然不危及生命，却因面部累及及慢性病程带来显著心理、社会和经济影响。患者常伴随焦虑、自卑和抑郁，严重影响生活质量8 。在经济层面，美国每年痤疮治疗相关支出超过12亿美元 9，在欧洲和中国，患者的就诊和药物花费也逐年增加。由此可见，痤疮不仅是临床最常见的皮肤病之一，更是亟待关注的重要公共卫生问题。背景概述在过去十年中，痤疮的诊断、分型及治疗理念经历了显著的演变。诊断方面，痤疮的典型皮损特征已得到广泛认可，但严重程度分级方法始终未能统一。目前常用的分级工具包括全球痤疮分级系统（GAGS）、研究者总体评估（IGA）以及法国的GEA系统等10 。这些工具在临床和研究中均有应用，但缺乏统一的“金标准”，限制了跨研究的数据比较和循证证据的累积。近年来，随着人工智能技术的引入，影像学辅助诊断逐渐应用于痤疮分级与疗效监测，可通过自动识别病灶实现更客观的评估11。指南的不断更新反映了治疗理念的演变与趋同。美国皮肤科学会（AAD）在2016年发布了循证指南，并于2024年进行了修订12,13；欧洲S3循证指南在2016年完成更新 14；中国也在2019年发布了新版指南5。总体而言，各国指南在分型分级治疗的核心原则上已形成共识：轻中度患者以外用药物为主，首选维甲酸类、过氧化苯甲酰及必要时联合抗生素；重度患者则推荐系统治疗，其中口服异维A酸依然是公认的“金标准”，但使用剂量、疗程等和以往有所不同，逐渐淡化了累积剂量，更加强调低剂量长疗程治疗，最大程度减少不良反应发生。尽管如此，不同地区在细节上仍存在差异。中国指南在强调药物治疗的同时，更突出生活方式和皮肤护理干预，包括饮食、作息和护肤教育，而欧美指南对此的着墨相对较少。近十年来，痤疮研究逐渐从传统的病因学探讨转向多组学整合与新型干预探索。遗传学和多族裔 GWAS 鉴定出新的易感位点，提示皮肤屏障与免疫调控在痤疮中的核心作用 15。微生物组研究揭示痤疮丙酸杆菌亚株在致病性上的差异，强化了“功能失衡而非数量增加”的观点，并推动了噬菌体与微生物移植等创新策略的探索16。单细胞和空间组学进一步证实 NLRP3–IL-1β–Th17 轴在早期病灶中的激活17。与此同时，人工智能在病灶识别与疗效评估中展现出临床价值18，新型递药方式（纳米载体、可溶性微针）及免疫调节剂也不断涌现，为精准与个体化治疗奠定了基础。在治疗手段方面，传统的维甲酸类、过氧化苯甲酰和抗生素仍然是基础，但新型药物不断出现。Trifarotene 作为首个选择性 RAR-γ 激动剂在疗效和耐受性方面表现出优势19；Clascoterone 作为外用雄激素受体拮抗剂，尽管疗效上仍未达到理想目标，但为油脂驱动型痤疮提供了新的治疗机制和思路20；4%米诺环素泡沫剂（FMX101）是一种新型外用抗生素制剂，已在美国和中国获批上市，Ⅲ期随机对照试验证实其在中重度痤疮患者中具有良好的疗效与耐受性，可显著减少炎性及非炎性皮损21。与此同时，光动力疗法、能量设备以及新型经皮递药技术正在被探索用于难治性或伴瘢痕的痤疮患者。尽管取得了进展，痤疮的诊治仍面临诸多挑战。严重程度分级和疗效评价体系尚未统一，影响了多中心研究结果的整合与推广。抗生素耐药问题日益严峻，部分地区痤疮丙酸杆菌对红霉素和克林霉素的耐药率已超过 80%22 。个体化治疗依然不足，缺乏能够预测疗效和复发风险的生物标志物。此外，痤疮后瘢痕与炎症后色素沉着依然是长期困扰患者的重要结局。总体来看，国际研究重点正在从传统的经验管理逐步过渡到精准医学。未来，建立统一的分级体系、加强耐药性管理、推动新药研发并注重长期结局改善，将是痤疮研究和管理的重要方向。热点聚焦过去十年，随着分子生物学、微生物组学、免疫学和药物递送技术的发展，痤疮的发病机制研究及治疗策略取得了重要突破。这些进展推动痤疮治疗进入精准化时代，为难治性患者提供更多选择。 1.痤疮发病机制的新认识 ① 全基因组关联分析（GWAS）在过去十年中极大推进了我们对痤疮遗传基础的理解。2014年，何黎教授团队通过对数千例重度痤疮患者进行GWAS研究，首次鉴定了SELL（选择素L）和DDB2（DNA损伤结合蛋白2）等重型痤疮易感基因位点(23)。这些基因分别参与雄激素代谢、炎症反应及疤痕形成等病理过程。其中，SELL基因编码的L-选择素作为中性粒细胞黏附迁移的关键调控因子，其功能变异可能导致炎症细胞在毛囊皮脂腺单元的异常聚集23。CRELD2、TIMP4和SEMA4B被确认为风险基因，而SLC22A5、SLC22A4、PDGFB、DEXI 和 PDLIM4则表现出显著的保护效应24。基于这些发现，研究者提出SLC22A5激动剂和CRELD2抑制剂可能成为新型靶向治疗策略，为精准医疗提供了理论依据24。 ② 微生物组学研究领域也取得突破性进展。通过全基因组测序和系统发育分析，痤疮丙酸杆菌被重新划分为Ⅰ型（含A1、A2、B、C亚型）、Ⅱ型和Ⅲ型。值得注意的是，Ⅰ型菌株与痤疮病变显著相关，而Ⅱ型则主要定植于健康皮肤25。最新研究揭示，皮肤疾病（特应性皮炎和痤疮）和身体部位决定了痤疮丙酸杆菌基因组的差异，这种致病性差异源于水平基因转移和适应性进化：与金黄色葡萄球菌相比，痤疮丙酸杆菌虽具有相对稳定的基因组和较少的毒力因子，但其在皮脂富集环境中可激活角质形成细胞的炎症通路26。痤疮丙酸杆菌存在显著的体部位定植特异性，这种生态位适应可能为开发部位特异性微生态制剂指明方向。此外，作为皮肤正常菌群，微生物不再简单的认为是痤疮发生的致病因素，可能在调节皮肤尤其是毛囊稳态中发挥重要作用，甚至可能参与调节了毛囊皮脂腺的稳态27,28。近年研究显示口服益生菌有助于痤疮治疗，痤疮患者使用健康型痤疮丙酸杆菌活菌作为外用益生菌治疗后皮肤中c痤疮丙酸杆菌分型多样性增加，非炎症性粉刺数量减少29,30。 ③ 在炎症机制研究方面，2024年免疫学期刊发表的成果证实，NLRP3炎症小体与NETosis（中性粒细胞胞外诱捕网介导的细胞死亡）形成正反馈循环，共同加剧痤疮炎症级联反应31。通过靶向抑制NETosis可显著减轻痤疮丙酸杆菌诱导的皮肤炎症，这为临床治疗提供了新思路。此外，皮脂腺细胞的多重功能被重新定义：除传统认知的皮脂分泌外，它们还能通过分泌趋化因子招募中性粒细胞、单核细胞等免疫细胞，并促进Th17细胞分化32。最新动物实验还发现，痤疮丙酸杆菌可诱导真皮成纤维细胞启动脂肪生成程序，分化为具有抗菌功能的前脂肪细胞，这一发现为理解皮肤免疫-代谢交互作用开辟了新视角33。 ④ 毛囊皮脂腺导管的角化方面，突破了传统的脂质和炎症因子的诱导角化的观点，越来越多的研究显示毛囊皮脂腺干细胞分化在调节毛囊角化和皮脂腺分化上存在平衡，相关因素引起平衡的破坏与毛囊角化和脂质分泌密切相关，未来调节毛囊皮脂腺干细胞分化的方向是治疗痤疮尤其是轻中度痤疮前景方向34,35。展望未来，痤疮研究将向多维度纵深发展：在遗传层面，单细胞测序技术有望解析易感基因的细胞特异性表达模式；微生物组研究需建立菌株-宿主互作的全景图谱，推动噬菌体疗法的临床转化；炎症机制方面，针对NETosis-NLRP3轴的双靶点抑制剂开发或将成为治疗突破点。随着类器官和器官芯片等技术的应用，下一代研究或将揭示痤疮发病的时空动态规律，最终实现从基础研究到个性化治疗的跨越。 2.治疗领域的重大进展 2019年，Trifarotene（Aklief）作为首个选择性靶向γ型维A酸受体（RAR-γ）的外用药问世，在维持抗炎效果的同时显著降低皮肤刺激发生率。同年，FDA批准4%米诺环素泡沫剂用于治疗9岁以上非结节性中重度痤疮患者的炎症性病变，我国III期临床试验进一步证实其可显著减少炎性和非炎性皮损21。此外，NAC-GED（选择性PPARγ调节剂）的Ⅱ期试验显示，5% NAC-GED凝胶可改善研究者整体评分（IGA）并减少总皮损数，疗效优于对照组36。在传统药物优化方面，2021年获批的Twyneo乳膏通过创新的微囊化缓释技术，成功解决了维A酸和过氧化苯甲酰（BPO）的配伍难题。临床研究显示，这种复方制剂可显著减少炎性皮损并减少不良反应。微胶囊化技术不仅提高了药物稳定性，还实现了活性成分的梯度释放。此外，微胶囊化过氧化苯甲酰及克林霉素+维A酸复方制剂可提高疗效并减少耐药性。 Clascoterone（Winlevi）的获批开创了局部抗雄激素治疗的新纪元。其独特的作用机制直接靶向皮脂腺雄激素受体，临床数据显示其可减少炎性喝非炎性皮损数量，且无系统性激素影响20。新型递药系统（如纳米颗粒、外泌体载体、微针等）的发展提高了药物靶向性，减少全身副作用37,38。光动力疗法（PDT）在难治性痤疮中展现出潜力39,40，而激素皮损内注射可作为辅助治疗。对于痤疮瘢痕和炎症后红斑，激光（Nd:YAG）也可起到良好改善效果41。系统治疗方面，异维A酸仍是痤疮治疗的"金标准"，近年来提出的低剂量异维a酸疗法可在不降低疗效的同时，显著减少皮肤干燥等副作用。2018年FDA批准了Seysara（sarecycline），用于治疗9岁及以上患者的非结节性中度至重度寻常痤疮的炎症性病变，该药对痤疮丙酸杆菌更具针对性，且对肠道菌群影响较小，安全性更优。为应对耐药性问题，新型疗法不断涌现。研究发现1A1型菌株高表达促炎因子CAMP2，注射于皮损部位的靶向CAMP的疫苗有望成为新的治疗方法42,43。除此之外，基于CRISPR-Cas的微生物组精准编辑技术通过噬菌体递送系统，或可选择性清除皮肤微生物组中的特定致病菌株。该技术利用核酸酶特异性识别并切割目标细菌的基因组序列，可精准清除致病菌株而不影响共生菌群。这种创新方法为痤疮治疗提供了微生物组层面的精准调控策略，既可治疗现有炎症症状，又能从根源上预防疾病发生。对于特殊人群，锌制剂可用于孕妇痤疮的抗炎治疗，而女性患者可选择复方口服避孕药，其疗效与口服抗生素相当，有助于减少抗生素滥用44。专家简介鞠强主任医师上海交通大学医学院附属仁济医院主任医师、博士生导师上海交通大学医学院附属仁济医院皮肤科主任上海市医学会皮肤科分会副主任委员中国医师协会皮肤科医师分会常务委员兼痤疮学组组长中国研究型医院学会皮肤科学专业委员会副主任委员中国人体健康促进会皮肤科分会秘书长中国康复学会皮肤科分会副会长兼痤疮学组组长中国中西医结合学会皮肤性病专业委员会常务委员中国非公医疗机构协会皮肤科分会常务委员兼痤疮学组组长中国整形协会皮肤美容分会常务委员上海市卫生系统优秀学科带头人“新百人” Dermatology助理编委，中华皮肤科杂志、实用皮肤科杂志及中国中西医结合皮肤病杂志编委。参考文献 1.Tan JKL, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015 July;172 Suppl 1:3–12. 2. Lynn DD, Umari T, Dunnick CA, Dellavalle RP. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther. 2016;7:13–25. 3. Tanghetti EA, Kawata AK, Daniels SR, Yeomans K, Burk CT, Callender VD. Understanding the burden of adult female acne. J Clin Aesthet Dermatol. 2014 Feb;7(2):22–30. 4. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999 Oct;41(4):577–80. 5. 鞠强. 中国痤疮治疗指南（2019修订版）. 临床皮肤科杂志. 2019;(48(09)):583-588. 6. Shen Y, Wang T, Zhou C, Wang X, Ding X, Tian S, et al. Prevalence of acne vulgaris in Chinese adolescents and adults: a community-based study of 17,345 subjects in six cities. Acta Derm Venereol. 2012 Jan;92(1):40–4. 7. Zhu Z, Zhong X, Luo Z, Liu M, Zhang H, Zheng H, et al. Global, regional and national burdens of acne vulgaris in adolescents and young adults aged 10-24 years from 1990 to 2021: a trend analysis. Br J Dermatol. 2025 Jan 24;192(2):228–37. 8. Samuels DV, Rosenthal R, Lin R, Chaudhari S, Natsuaki MN. Acne vulgaris and risk of depression and anxiety: A meta-analytic review. J Am Acad Dermatol. 2020 Aug;83(2):532–41. 9. Adams JA, Adams AJ, Klepser ME. Pharmacist Prescriptive Authority for Acne: An Evidence-Based Approach to Policy. Innov Pharm. 2021;12(2). 10. Ih B, Jh K, Ch N, Ms K, Bs S, H C. A Comprehensive Review of the Acne Grading Scale in 2023. Annals of dermatology [Internet]. 2024 Apr [cited 2025 Sept 10];36(2). Available from: https://pubmed.ncbi.nlm.nih.gov/38576244/ 11. Traini DO, Palmisano G, Guerriero C, Peris K. Artificial Intelligence in the Assessment and Grading of Acne Vulgaris: A Systematic Review. J Pers Med. 2025 June 6;15(6):238. 12. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 May;74(5):945-973.e33. 13. Reynolds RV, Yeung H, Cheng CE, Cook-Bolden F, Desai SR, Druby KM, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024 May;90(5):1006.e1-1006.e30. 14. Nast A, Dréno B, Bettoli V, Bukvic Mokos Z, Degitz K, Dressler C, et al. European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version. J Eur Acad Dermatol Venereol. 2016 Aug;30(8):1261–8. 15. Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, et al. Genome-wide association meta-analysis identifies 29 new acne susceptibility loci. Nat Commun. 2022 Feb 7;13(1):702. 16. A R, C R, V L, S SL, Sa O, T S, et al. Topical phage therapy in a mouse model of Cutibacterium acnes-induced acne-like lesions. Nature communications [Internet]. 2023 Feb 22 [cited 2025 Sept 10];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/36813793/ 17. Deng M, Odhiambo WO, Qin M, To TT, Brewer GM, Kheshvadjian AR, et al. Analysis of intracellular communication reveals consistent gene changes associated with early-stage acne skin. Cell Commun Signal. 2024 Aug 14;22(1):400. 18. Gao N, Wang J, Zhao Z, Chu X, Lv B, Han G, et al. Evaluation of an acne lesion detection and severity grading model for Chinese population in online and offline healthcare scenarios. Sci Rep. 2025 Jan 7;15(1):1119. 19. Tan J, Thiboutot D, Popp G, Gooderham M, Lynde C, Del Rosso J, et al. Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol. 2019 June;80(6):1691–9. 20. Hebert A, Thiboutot D, Stein Gold L, Cartwright M, Gerloni M, Fragasso E, et al. Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials. JAMA Dermatol. 2020 June 1;156(6):621–30. 21. Le Y, Yang W, Lu J, Jiang X, Guo Q, Huang C, et al. Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study. J Eur Acad Dermatol Venereol. 2025 May;39(5):967–75. 22. Zhu C, Wei B, Li Y, Wang C. Antibiotic resistance rates in Cutibacterium acnes isolated from patients with acne vulgaris: a systematic review and meta-analysis. Front Microbiol. 2025;16:1565111. 23. He L, Wu WJ, Yang JK, Cheng H, Zuo XB, Lai W, et al. Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne. Nat Commun. 2014;5:2870. 24. Qiu X, Feng Y, Mo X, Ju Q. Multi-omics Analysis Identifies Genetic Mechanisms and Therapeutic Targets for Acne Vulgaris. J Invest Dermatol. 2025 May 19;S0022-202X(25)00487-7. 25. Tomida S, Nguyen L, Chiu BH, Liu J, Sodergren E, Weinstock GM, et al. Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. mBio. 2013 Apr 30;4(3):e00003-00013. 26. T Y, X X, Y L, X W, S W, Z Q, et al. Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin. Cell host & microbe [Internet]. 2024 Oct 7 [cited 2025 Sept 10];32(7). Available from: https://pubmed.ncbi.nlm.nih.gov/38936370/ 27. 毛囊皮脂腺微生态与痤疮. 实用皮肤病学杂志. 2019;(02 vo 12):94-97+101. 28. Almoughrabie S, Cau L, Cavagnero K, O’Neill AM, Li F, Roso-Mares A, et al. Commensal Cutibacterium acnes induce epidermal lipid synthesis important for skin barrier function. Sci Adv. 2023 Aug 18;9(33):eadg6262. 29. Goodarzi A, Mozafarpoor S, Bodaghabadi M, Mohamadi M. The potential of probiotics for treating acne vulgaris: A review of literature on acne and microbiota. Dermatol Ther. 2020 May;33(3):e13279. 30. Karoglan A, Paetzold B, Pereira de Lima J, Brüggemann H, Tüting T, Schanze D, et al. Safety and Efficacy of Topically Applied Selected Cutibacterium acnes Strains over Five Weeks in Patients with Acne Vulgaris: An Open-label, Pilot Study. Acta Derm Venereol. 2019 Dec 1;99(13):1253–7. 31. Kim HJ, Lee YS, Lee BS, Han CH, Kim SG, Kim CH. NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment. Cell Mol Immunol. 2024 May;21(5):466–78. 32. Mattii M, Lovászi M, Garzorz N, Atenhan A, Quaranta M, Lauffer F, et al. Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells. Br J Dermatol. 2018 Mar;178(3):722–30. 33. O’Neill AM, Liggins MC, Seidman JS, Do TH, Li F, Cavagnero KJ, et al. Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne. Sci Transl Med. 2022 Feb 16;14(632):eabh1478. 34. Cao K, Chen G, Chen W, Hou X, Hu T, Lu L, et al. Formalin-killed Propionibacterium acnes activates the aryl hydrocarbon receptor and modifies differentiation of SZ95 sebocytes in vitro. Eur J Dermatol. 2021 Feb 1;31(1):32–40. 35. 鞠强, 李嘉祺. 寻常痤疮再认识：从发病机制到治疗策略. 中华皮肤科杂志. 2024 Apr 15;57(04):289–94. 36. Picardo M, Cardinali C, La Placa M, Lewartowska-Białek A, Lora V, Micali G, et al. Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial. Br J Dermatol. 2022 Oct;187(4):507–14. 37. Cao W yu, Zhao H qing, Gu X, Shao W jun, Zheng L jie, Zeng Q ya, et al. Light-responsive antibacterial dissolving microneedles loaded with 5-aminolevulinic acid and silver nanoparticles for the treatment of acne. International Journal of Pharmaceutics. 2024 Dec 25;667:124961. 38. Xiang Y, Lu J, Mao C, Zhu Y, Wang C, Wu J, et al. Ultrasound-triggered interfacial engineering-based microneedle for bacterial infection acne treatment. Sci Adv. 9(10):eadf0854. 39. Pariser DM, Eichenfield LF, Bukhalo M, Waterman G, Jarratt M, PDT Study Group. Photodynamic therapy with methyl aminolaevulinate 80 mg g(-1) for severe facial acne vulgaris: a randomized vehicle-controlled study. Br J Dermatol. 2016 Apr;174(4):770–7. 40. Zhang L, Yang Y, Wang B, Zhao Y, Wang P, Liu J, et al. Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study. J Am Acad Dermatol. 2023 Dec;89(6):1141–8. 41. Panchaprateep R, Munavalli G. Low-fluence 585 nm Q-switched Nd:YAG laser: a novel laser treatment for post-acne erythema. Lasers Surg Med. 2015 Feb;47(2):148–55. 42. Valanne S, McDowell A, Ramage G, Tunney MM, Einarsson GG, O’Hagan S, et al. CAMP factor homologues in Propionibacterium acnes: a new protein family differentially expressed by types I and II. Microbiology (Reading). 2005 May;151(Pt 5):1369–79. 43. Wang Y, Hata TR, Tong YL, Kao MS, Zouboulis CC, Gallo RL, et al. The Anti-Inflammatory Activities of Propionibacterium acnes CAMP Factor-Targeted Acne Vaccines. J Invest Dermatol. 2018 Nov;138(11):2355–64. 44. Dréno B. [The treatment of acne]. Presse Med. 2005 Apr 9;34(7):540–3. 撰稿丨阮丹丹、杨雪帆、邱欣澜审校丨鞠强排版丨叶子点击“阅读原文” 解锁您的“优麦拾光纪念册”

临床研究

2025-12-17

·GlobeNewswire-Health Care

Sol-Gel Provides Update Following Unblinding of Phase 1b Study of SGT-210 in Darier Disease

NESS ZIONA, Israel, Dec. 17, 2025 (GLOBE NEWSWIRE) -- Sol-Gel Technologies, Ltd. (NASDAQ: SLGL), a dermatology company, pioneering treatments for patients with rare and severe skin conditions, today provided an update following the unblinding of clinical data from its vehicle-controlled proof-of-concept Phase 1b study of SGT-210 on Darier disease. Following unblinding, the data from the vehicle-controlled Phase 1b proof-of-concept study did not show differentiation between SGT-210 and vehicle on the study’s efficacy assessments. Mr. Mori Arkin, Executive Chairman of Sol-Gel, stated: "After unblinding the clinical data from our trial, the study did not demonstrate a signal of superiority of active treatment versus vehicle, and we have therefore decided not to advance to the next stage of development in this indication. We intend to pursue very small, low-cost feasibility studies in other areas of unmet medical need where the mechanistic rationale for SGT-210 is strong. We continue to prioritize the successful completion of our Phase 3 program of SGT-610 in Gorlin syndrome and preparatory activities supporting a potential Phase 3 program in high-frequency BCC, subject to successful completion of the Gorlin Phase 3 trial." About Gorlin Syndrome and SGT-610 SGT-610, a hedgehog signaling pathway blocker, has the potential to be the first ever treatment for prevention of BCCs in Gorlin syndrome patients, if approved. Gorlin syndrome, an autosomal dominant genetic disorder affecting approximately 1 in 27,000-31,000 people in the U.S., is mostly caused by inheritance of one defective copy of the tumor suppressor patched homolog 1 (PTCH1) gene. Normally, the PTCH1 gene blocks the smoothened, frizzle class receptor (SMO) gene, turning off the hedgehog signaling pathway when it is not needed. Mutations in the PTCH1 gene may cause a loss of PTCH1 function, release of SMO, and may allow BCC tumor cells to divide uncontrollably. Patidegib, the active substance in SGT-610, is designed to block the SMO signal, thus, allowing cells to function normally and reducing the production of new tumors. About Sol-Gel Technologies Sol-Gel Technologies Ltd. is a dermatology company focused on identifying, developing and commercializing or partnering drug products to treat skin diseases. Sol-Gel developed TWYNEO which is approved by the FDA for the treatment of acne vulgaris in adults and pediatric patients nine years of age and older; and EPSOLAY, which is approved by the FDA for the treatment of inflammatory lesions of rosacea in adults. The Company’s pipeline also includes Phase 3 clinical trial of Orphan and breakthrough drug candidate SGT-610, which is a new topical hedgehog inhibitor being developed to prevent the new basal cell carcinoma lesions in patients with Gorlin syndrome that is expected to have an improved safety profile compared to oral hedgehog inhibitors as well as topical drug candidate SGT-210 under investigation for the treatment of rare hyper keratinization disorders. For additional information, please visit our new website: www.sol-gel.com Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to statements regarding the successful completion of Phase 3 program of SGT-610 in Gorlin syndrome and a potential Phase 3 program in high-frequency BCC. In some cases, you can identify forward-looking statements by terminology such as “believe,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “expect,” “predict,” “potential,” or the negative of these terms or other similar expressions. Forward-looking statements are based on information we have when those statements are made or our management’s current expectations and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. Important factors that could cause such differences include, but are not limited to, the risk that we will not successfully complete the Gorlin Phase 3 trial or that it will be delayed, that we will not commence a potential Phase 3 program in high-frequency BCC, and if we do that it will not be successful, the risk that the market for SGT-610 and SGT-210 will not be as anticipated, including with respect to High-Frequency BCC for SGT-610, our ability to enter into further collaborations, a delay in the timing of our clinical trials, top-line results and regulatory filings, the success of our clinical trials, and an increase in our anticipated costs and expenses, as well as the following factors: (i) the adequacy of our financial and other resources, particularly in light of our history of recurring losses and the uncertainty regarding the adequacy of our liquidity to pursue our complete business objectives; (ii) our ability to complete the development of our product candidates; (iii) our ability to find suitable co-development partners; (iv) our ability to obtain and maintain regulatory approvals for our product candidates in our target markets, the potential delay in receiving such regulatory approvals and the possibility of adverse regulatory or legal actions relating to our product candidates even if regulatory approval is obtained; (v) our collaborators’ ability to commercialize our pharmaceutical product candidates; (vi) our ability to obtain and maintain adequate protection of our intellectual property; (vii) our collaborators’ ability to manufacture our product candidates in commercial quantities, at an adequate quality or at an acceptable cost; (viii) our collaborators’ ability to establish adequate sales, marketing and distribution channels; (ix) acceptance of our product candidates by healthcare professionals and patients; (x) the possibility that we may face third-party claims of intellectual property infringement; (xi) the timing and results of clinical trials that we may conduct or that our competitors and others may conduct relating to our or their products; (xii) intense competition in our industry, with competitors having substantially greater financial, technological, research and development, regulatory and clinical, manufacturing, marketing and sales, distribution and personnel resources than we do; (xiii) potential product liability claims; (xiv) potential adverse federal, state and local government regulation in the United States, China, Europe or Israel; and (xv) loss or retirement of key executives and research scientists; (xvi) general market, political and economic conditions in the countries in which the Company operates; and, (xvii) the current war between Israel and Hamas and any deterioration of the war in Israel into a broader regional conflict involving Israel with other parties. These factors and other important factors discussed in the Company's Annual Report on Form 20-F filed with the Securities and Exchange Commission (“SEC”) on March 13, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Except as required by law, we undertake no obligation to update any forward-looking statements in this press release. Sol-Gel Contact:Eyal Ben-Or Chief Financial Officerinfo@sol-gel.com+972-8-9313429 Source: Sol-Gel Technologies Ltd.

临床1期临床3期上市批准临床结果

2025-12-15

·iobiotech.com

IO Biotech Announces Publication of Five-year Clinical Outcomes of Phase 1/2 Trial in Nature Communications

Findings provide scientific insights into the contributions of IDO1 and PD-L1 vaccination to PD-1 blockade for the treatment of metastatic melanoma Five-year analysis of median progression free survival was 25.5 months These results reinforce the potential of immune-modulatory vaccination NEW YORK, Dec. 15, 2025 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, today announced the publication in Nature Communications of the long-term clinical and immunological outcomes from MM1636, the Phase 1/2 trial evaluating the investigational peptide vaccine IO102-IO103 targeting both tumor cells and immune-suppressive cells expressing IDO1 and/or PD-L1, in combination with PD-1 blockade in the treatment of first line metastatic melanoma. The results of this trial supported a Breakthrough Therapy Designation for the treatment of unresectable/metastatic melanoma in combination with pembrolizumab by the US Food and Drug Administration (FDA) and, together with the available preclinical and translational data, served as the foundation for IO Biotech’s decision to initiate the Phase 3 clinical trial in first-line advanced melanoma (IOB-013/KN-D18). The MM1636 results published today showed the five-year follow-up analysis of IO102-IO103 in combination with nivolumab in patients with metastatic melanoma, demonstrating durable clinical activity with a 25.5-month median progression-free survival (PFS). The results also showed the identification of potential vaccine-specific immune biomarkers of long-term benefit, not observed in a matched anti-PD-1 monotherapy cohort, suggesting a distinct vaccine-induced immune modulation increasing anti-tumor activity. These overall results provide a compelling rationale for integrating immune-modulatory vaccination into immunotherapy regimens for patients with melanoma. “These are very exciting data that continue reinforcing the scientific foundation of our immune-modulatory therapeutic approach and strengthens our belief in its potential to transform patient care,” said Mads Hald Andersen, DMSc, PhD, Director of the Center for Cancer Immune Therapy (CCIT) and scientific co-founder of IO Biotech. “IDO1 and PD-L1 are immune suppressive targets expressed in many cancers hence, we believe that IO102-IO103 could have pan-tumor activity. I am proud to be part of the team that is further developing this potential new treatment option.” “We are very encouraged that the long-term follow up data confirm the earlier results reported from this study. The notable median duration of response of more than 53 months and an impressive median overall survival of 60 months support the potential of IO102-IO103 as a first-line therapy for melanoma as part of a combination regimen.” said Inge Marie Svane, MD, PhD, Professor, Director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev, clinical co-founder of IO Biotech and Principal Investigator in the IOB-013 Phase 3 Trial. “There continues to be a significant unmet need for innovative therapies that improve outcomes for cancer patients,” said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. “These data strengthen our belief in Cylembio and in our approach to develop off-the-shelf, immune modulatory therapeutics, with pan-cancer potential.“ The article, titled “Five-year clinical outcome and immune biomarkers of durable response from the MM1636 trial on IDO/PD-L1 vaccination and PD-1 blockade in first line metastatic melanoma”, is now available online at https://www.nature.com/articles/s41467-025-67508-8. About IO Biotech IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines based on its T-win® platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target both tumor cells and the immune-suppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, Cylembio® (IO102-IO103), in clinical trials, and additional pipeline candidates through preclinical development. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York. For further information, please visit www.iobiotech.com. Follow us on our social media channels on LinkedIn and X (@IOBiotech). About the MM1636 Clinical Trial The MM1636 trial (ClinicalTrials.gov: NCT03047928), an investigator-initiated trial at the Copenhagen University Hospital, Herlev, enrolled 30 patients with metastatic melanoma. In this Phase 1/2 clinical trial, patients received the multi-antigen immunotherapeutic, IO102-IO103, in combination with the anti-programmed death 1 (PD-1) antibody nivolumab as first line treatment. Patients were treated with nivolumab according to the approved label for melanoma (3mg/kg bi-weekly for up to two years). IO102-IO103 was given from the start of administration of nivolumab and every second week for the first six weeks and thereafter, every fourth week for 41 weeks. The trial objectives were to assess safety, immune response in blood and biopsies as well as efficacy. About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) was an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio® (IO102-IO103) in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Enrollment in the trial was completed by December 2023 with a total of 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study was progression free survival. Secondary endpoints include overall response rate, overall survival, durable objective response rate, complete response rate, duration of response, time to complete response, disease control rate, and incidence of adverse events and serious adverse events (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed as exploratory endpoints. The company reported topline results from this trial in the third quarter of 2025. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab. Forward-Looking Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including statements regarding the timing or outcome of communications with regulatory authorities including the FDA, the timing or outcome of the submission of regulatory applications, including an IND for IO112, and statements regarding other current or future clinical trials, their timing, progress, enrollment or results, or the company’s financial position or cash runway, are based on IO Biotech’s current assumptions and expectations of future events and trends, which affect or may affect its business, strategy, operations or financial performance, and actual results and other events may differ materially from those expressed or implied in such statements due to numerous risks and uncertainties. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Because forward-looking statements are inherently subject to risks and uncertainties, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Except to the extent required by law, IO Biotech undertakes no obligation to update these statements, whether as a result of any new information, future developments or otherwise. Contact: Investors and media:Maryann Cimino, Director of Investor Relations & Corporate CommunicationsIO Biotech, Inc.617-710-7305mci@iobiotech.com

临床3期临床结果免疫疗法疫苗突破性疗法

100 项与过氧苯甲酰/维A酸相关的药物交易

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适应症	国家/地区	公司	日期
寻常痤疮	美国	Mayne Pharma Ltd.	2021-07-26

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03664739 (CTgov)	临床3期	寻常痤疮	608	IDP-120 (IDP-120 Gel)	憲齋顧淵壓糧蓋構選窪(網鏇鹽夢鬱繭網簾選積) = 鑰選廠簾構憲醖艱蓋襯選淵遞簾顧鹹鬱蓋淵齋 (淵觸鏇遞積餘壓觸網鬱, 10.79) 更多	-	2023-03-29
				IDp-120 (IDP-120 Vehicle Gel)	憲齋顧淵壓糧蓋構選窪(網鏇鹽夢鬱繭網簾選積) = 獵顧淵衊廠衊繭築鹽夢選淵遞簾顧鹹鬱蓋淵齋 (淵觸鏇遞積餘壓觸網鬱, 9.68) 更多
NCT03664752 (CTgov)	临床3期	寻常痤疮	585	IDP-120 (IDP-120 Gel)	憲醖糧鹽顧製蓋築範餘(鏇繭廠積構顧齋製構夢) = 夢壓糧襯獵醖醖積鹹簾獵鏇壓醖蓋膚觸衊夢糧 (糧範築鬱淵鏇鏇醖構齋, 9.50) 更多	-	2023-03-29
				IDP-120 (IDP-120 Vehicle Gel)	憲醖糧鹽顧製蓋築範餘(鏇繭廠積構顧齋製構夢) = 齋窪憲糧獵遞觸醖鹽簾獵鏇壓醖蓋膚觸衊夢糧 (糧範築鬱淵鏇鏇醖構齋, 9.80) 更多
NCT03761810 (SGT-65-05, CTgov)	临床3期	寻常痤疮	434	S6G5T-3 (S6G5T-3)	齋醖襯艱淵艱餘衊網積 = 鏇構鹹觸衊夢襯糧衊襯夢願醖夢衊鬱獵衊醖選 (蓋淵鏇膚餘鏇網觸範鹽, 衊衊顧餘網願網製鏇構 ~ 製蓋築繭餘襯淵構廠廠) 更多	-	2021-12-01
				S6G5T-8 (S6G5T-8 Vehicle Cream)	齋醖襯艱淵艱餘衊網積 = 網鹽窪壓製積壓積鬱積夢願醖夢衊鬱獵衊醖選 (蓋淵鏇膚餘鏇網觸範鹽, 鹹蓋襯觸鬱顧築餘願鹹 ~ 艱範遞齋繭襯糧艱鹹膚) 更多
NCT03761784 (SGT-65-04, CTgov)	临床3期	寻常痤疮	424	S6G5T-3 (S6G5T-3)	積觸鑰夢觸壓鑰鑰膚鹽 = 衊淵壓鑰遞鹽觸鬱襯醖積顧醖簾鏇願繭壓膚艱 (積衊襯製齋膚壓構糧齋, 夢餘鏇鹽範醖淵鬱餘膚 ~ 襯襯衊糧遞鏇鬱艱觸鬱) 更多	-	2021-12-01
				S6G5T-8 (S6G5T-8 Vehicle Cream)	積觸鑰夢觸壓鑰鑰膚鹽 = 觸網積糧餘夢蓋鏇繭齋積顧醖簾鏇願繭壓膚艱 (積衊襯製齋膚壓構糧齋, 衊簾鑰積積製選鹽蓋選 ~ 窪衊獵餘遞積構夢鹽夢) 更多
NCT03761784 (SGT-65-04, GlobeNewswire) 人工标引	临床3期	寻常痤疮	424	Benzoyl Peroxide+Twyneo	廠壓願遞遞築鹹膚製憲(選餘衊夢膚鑰簾壓鏇願) = 獵襯廠壓遞獵膚獵簾鑰築醖觸鬱網選繭衊膚糧 (鬱齋製窪艱獵觸蓋艱繭 ) 更多	积极	2019-12-30
				Placebo	廠壓願遞遞築鹹膚製憲(選餘衊夢膚鑰簾壓鏇願) = 鹽醖構壓鹹鬱選襯鏇繭築醖觸鬱網選繭衊膚糧 (鬱齋製窪艱獵觸蓋艱繭 ) 更多
NCT03761810 (SGT-65-05, GlobeNewswire) 人工标引	临床3期	寻常痤疮	434	Benzoyl Peroxide+Twyneo	構窪壓夢選鬱鏇網廠選(襯製構觸糧蓋襯築鏇繭) = 廠簾獵壓餘艱遞築遞膚齋蓋艱製製壓顧鑰選鹹 (觸憲鑰艱繭窪範衊艱獵 ) 更多	积极	2019-12-30
				Placebo	構窪壓夢選鬱鏇網廠選(襯製構觸糧蓋襯築鏇繭) = 製餘範願鏇淵繭製遞醖齋蓋艱製製壓顧鑰選鹹 (觸憲鑰艱繭窪範衊艱獵 ) 更多