Anacaulase-bcdb

Secured additional R&D collaborations with Solventum and Mölnlycke for optimal trial consistency and patient outcomes Study to support EscharEx® BLA submission and strengthen commercialization strategy YAVNE, Israel, Oct. 10, 2024 (GLOBE NEWSWIRE) -- MediWound Ltd. (Nasdaq: MDWD), the global leader in next-generation enzymatic therapeutics for tissue repair, today announced that it will be initiating a controlled, multicenter Phase II clinical study evaluating EscharEx® against collagenase ointment (marketed as SANTYL® in the U.S. and IRUXOL® in Europe) for the treatment of venous leg ulcers (VLUs). Scheduled to commence in 2025, this Phase II study will run concurrently with the Company’s Phase III trial in VLU patients. The study is designed to support the Biologics License Application (BLA) for EscharEx and plays a key role in MediWound’s commercialization strategy. Ofer Gonen, CEO of MediWound, stated: "Building on the consistent positive results from three prior Phase II studies of EscharEx, we are eager to further validate our earlier findings from the head-to-head comparison vs. SANTYL, now on a larger, global scale. We are confident that EscharEx will demonstrate superior efficacy, addressing critical unmet needs in enzymatic debridement for patients with chronic wounds." The randomized, prospective study will enroll 45 patients across multiple sites in the U.S. and Europe. VLU patients will be randomly assigned in a 1:1:1 ratio to receive either EscharEx, placebo, or collagenase. In the first two weeks, the EscharEx and placebo groups will receive up to 8 daily applications, while the collagenase group will follow the product’s instructions for use (IFU). Each patient’s participation will last up to 14 weeks. Key safety endpoints, including the incidence and severity of adverse events (AEs), and time to complete wound closure, will be assessed. Additionally, exploratory efficacy endpoints will evaluate the incidence and time to complete debridement, granulation tissue formation, and wound bed preparation. To support this trial, MediWound has formed additional strategic R&D collaborations with Solventum and Mölnlycke Health Care. Solventum will supply the Coban™ 2 Two-Layer Compression System, while Mölnlycke will provide Mepilex®, Mepilex® Ag, Exufiber®, and Exufiber® Ag. These partnerships are designed to enhance consistency across study arms and ensure the use of best-in-class products, ultimately benefiting patient outcomes. About EscharEx EscharEx® is a bioactive, multimodal debridement therapy for the treatment of chronic and other hard-to-heal wounds, currently in the advanced stages of clinical development. It is a concentrate of proteolytic enzymes, enriched with bromelain, designed for topical and easy-to-use daily applications. In three previous Phase II trials, EscharEx was shown to be safe and well-tolerated. It demonstrated efficacy in debridement, the promotion of granulation tissue, and the reduction of bioburden and biofilm in various hard-to-heal wounds, effectively preparing the wound bed for healing. MediWound is set to initiate a Phase III study for Venous Leg Ulcers in the second half of 2024. Preparations for a Phase II/III study targeting Diabetic Foot Ulcers are underway. About MediWound MediWound Ltd. (Nasdaq: MDWD) is a global leader in next-generation enzymatic therapeutics focused on non-surgical tissue repair. The Company specializes in the development, production and commercialization of rapid and effective biologics that enhance existing standards of care and improve patient experiences while reducing healthcare costs and unnecessary surgeries. MediWound’s first drug, NexoBrid®, is FDA and EMA-approved as an orphan biologic for eschar removal in deep partial-thickness and/or full-thickness thermal burns, significantly reducing the need for surgical interventions. Building on its proprietary enzymatic platform, MediWound is advancing EscharEx®, a promising candidate currently in Phase III development for the debridement of chronic wounds. With distinct advantages over the current $360+ million market leader, EscharEx offers a unique opportunity for significant market expansion. For more information visit www.mediwound.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements MediWound cautions you that all statements other than statements of historical fact included in this press release that address activities, events, or developments that we expect, believe, or anticipate will or may occur in the future are forward-looking statements. Although we believe that we have a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting us and are subject to risks, assumptions, uncertainties, and factors, all of which are difficult to predict and many of which are beyond our control. Actual results may differ materially from those expressed or implied by the forward-looking statements in this press release. These statements are often, but are not always, made through the use of words or phrases such as “anticipates,” “intends,” “estimates,” “plans,” “expects,” “continues,” “believe,” “guidance,” “outlook,” “target,” “future,” “potential,” “goals” and similar words or phrases, or future or conditional verbs such as “will,” “would,” “should,” “could,” “may,” or similar expressions. Specifically, this press release contains forward-looking statements concerning the anticipated progress, development, study design, expected data timing, objectives anticipated timelines, expectations and commercial potential of our products and product candidates, including EscharEx®. Among the factors that may cause results to be materially different from those stated herein are the inherent uncertainties associated with the uncertain, lengthy and expensive nature of the product development process; the timing and conduct of our studies of our products and product candidates, including the timing, progress and results of current and future clinical studies, and our research and development programs; the approval of regulatory submission by the FDA, the European Medicines Agency or by any other regulatory authority, our ability to obtain marketing approval of our products and product candidates in the U.S. or other markets; the clinical utility, potential advantages and timing or likelihood of regulatory filings and approvals of our products and products; our expectations regarding future growth, including our ability to develop new products; market acceptance of our products and product candidates; our ability to maintain adequate protection of our intellectual property; competition risks; the need for additional financing; the impact of government laws and regulations and the impact of the current global macroeconomic climate on our ability to source supplies for our operations or our ability or capacity to manufacture, sell and support the use of our products and product candidates in the future. These and other significant factors are discussed in greater detail in MediWound’s annual report on Form 20-F for the year ended December 31, 2023, filed with the Securities and Exchange Commission (“SEC”) on March 21, 2024 and Quarterly Reports on Form 6-K and other filings with the SEC from time-to-time. These forward-looking statements reflect MediWound’s current views as of the date hereof and MediWound undertakes, and specifically disclaims, any obligation to update any of these forward-looking statements to reflect a change in their respective views or events or circumstances that occur after the date of this release except as required by law. MediWound Contacts:Hani LuxenburgChief Financial OfficerMediWound Ltd.ir@mediwound.comDaniel FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com Media Contact: Ellie HansonFINN Partners for MediWoundellie.hanson@finnpartners.com+1-929-588-2008

一、前言 凝胶剂（Gel）是指原料药与能形成凝胶的辅料制成的具凝胶特性的稠厚液体或半固体制剂。凝胶剂可分为全身用凝胶剂（Transdermal gel）和局部用凝胶剂（Topical gel）两类。按给药途径不同，可以进一步将局部用凝胶剂分为皮肤用凝胶剂、眼用凝胶剂、阴道用凝胶剂、直肠用凝胶剂等。 表12000年至2024年FDA批准的局部皮肤用凝胶剂产品（NDA） 笔者研通过调取FDA网站上发布的新药申请批准情况，收集了从2000年至2024年这25年时间里FDA批准上市（已撤市的产品不纳入统计）的具有专有名称的局部皮肤用凝胶剂产品。各产品的具体信息见表1和表2。从表中可以看出，从2000年至2024年，FDA共批准上市了26款局部皮肤用凝胶剂NDA上市申请，平均每年批准1款。 表22000年至2024年FDA批准的局部皮肤用凝胶剂产品处方组成 二、产品分析 2.1 凝胶基质选择 局部皮肤用凝胶剂的常用辅料有凝胶基质、pH调节剂、保湿剂、防腐剂、稳定剂、助溶剂、增溶剂及透皮吸收促进剂等。其中，凝胶基质的选择在凝胶制剂的处方开发中尤为重要。 在FDA批准的这26款局部皮肤用凝胶剂中，除Zelsuvmi用到了两种凝胶基质（羟丙基纤维素+羧甲基纤维素钠）外，其余25款均只用了一种凝胶基质。而在这25款产品中，共有16款使用了卡波姆（Carbomer）作为凝胶基质，占到总数的64%。其次是丙烯酰胺/丙烯酰基二甲基牛磺酸钠共聚物（3款，12%）、羟丙基纤维素（2款，8%）、羟乙基纤维素（2款，8%），黄原胶（1款，4%）、葵花油（1款，4%）。 2.1.1 卡波姆 卡波姆是凝胶剂中一种常用凝胶基质，常用比例为0.5%-2.0%。卡波姆是丙烯酸的高分子聚合物，结构中含有52%至68%的羧基基团，当使用中和剂（如氢氧化钠、三乙醇胺、氢氧化钾等）中和后其卷曲的分子会因电荷斥力而张开，从而显著增加其黏稠度，形成凝胶。 卡波姆有多种型号，包括卡波姆940、941、974、980、981等。在16款以卡波姆为凝胶基质的产品中，有6款使用了卡波姆980（占比37.5%），其次是卡波姆940（5款，31.25%）。卡波姆941、卡波姆981和卡波姆974等型号均各有一款产品（如上图所示）。 根据交联剂的不同可将卡波姆分为卡波姆均聚物、卡波姆共聚物和卡波姆互聚物。卡波姆940、941、974、980、981都属于卡波姆均聚物，即通过烯丙基蔗糖或季戊四醇烯丙基醚交联得到的丙烯酸聚合物。卡波姆940、941在合成过程中使用了苯作为聚合溶液，而如今药品辅料应用中对苯的使用限制越来越严格，因此这两种型号现在很少使用。卡波姆980、981在合成中使用环己烷和乙酸乙酯制成的共溶剂体系，适合作为外用凝胶制剂的凝胶基质；卡波姆980和981是卡波姆940和941的对应产品，若已在上市老品种中使用了卡波姆940和卡波姆941，则可以分别替换成卡波姆980和卡波姆981。卡波姆974使用乙酸乙酯作为聚合溶液，完全不含苯，是更为安全的一种卡波姆型号，可用于口服以及粘膜接触的制剂处方中。 2.1.2丙烯酰胺/丙烯酰基二甲基牛磺酸钠共聚物 法国Seppic公司开发的Sepineo P600主要由丙烯酰胺/丙烯酸二甲基牛磺酸钠共聚物（acrylamide/sodium acryloyldimethyl taurate copolymer）组成，这种共聚物被分散在异十六烷（isohexadecane）中，并以聚山梨酯80（polysorbate 80）作为稳定剂。在FDA批准的这26款局部皮肤用凝胶剂中，共有3款（见表2）使用到了到了这种凝胶基质。该凝胶基质具有自凝胶化、增稠和乳化油相的能力，适合用于凝胶和油包水乳胶剂（emulgel）的处方中，常用比例为1%-5%。Sepineo P600以液体形式存在，遇水时由于静电排斥作用，带负电的聚合物会瞬间膨胀，形成一个三维网络结构。在较低浓度下，Sepineo P 600就能提供较高的粘度，在广泛的pH范围内（3-12）都能保持稳定，这使其能够适应不同配方的需求，且与多种溶剂（如乙醇、甘油等）相容性良好。 2.1.3其它 羟丙基纤维素、羟乙基纤维素、羧甲基纤维素钠均为纤维素衍生物，也常用于外用凝胶剂的制备中，具有良好的生物相容性和安全性，由于型号以及生产厂家众多，因此使用方法及用量还应具体参考的产品说明书。 黄原胶（Xanthan gum）能够在溶液中形成不同形式的螺旋结构，并通过分子间的相互作用（如氢键、疏水作用等）形成复杂的网络结构，这种网络结构是黄原胶作为凝胶基质的基础。黄原胶是一种阴离子聚合物，这意味着它在水中电离后带有负电荷。由于电荷相互作用，黄原胶通常与阳离子表面活性剂、聚合物或防腐剂不兼容，因为它们之间的电荷吸引会导致沉淀现象的发生。黄原胶溶液能在含有高达60%的有机溶剂（如乙醇或异丙醇等）时保持稳定，这意味着黄原胶可以在这些溶剂的混合体系中作为凝胶基质使用。 葵花油（sunflower oil）严格意义上来说并不算是一种凝胶基质，目前它仅在Filsuvez这款产品中作为凝胶基质使用。Filsuvez的活性成分桦木三萜是从桦树皮中得到的提取物，由天然存在的三萜类物质组成，该处方中含有10%的桦木三萜和90%的葵花油。这种桦木三萜提取物可以使油类物质凝胶化，从而可以形成半固体、粘弹性的油凝胶（oleogel），并具有触变性。 2.2 适应症分析 FDA批准的这26款局部皮肤用凝胶剂NDA上市申请中，适应症以寻常痤疮居多，占到总数的一半（即50%）。其次是玫瑰痤疮（11.6%）、足藓（7.7%）、皮肤T细胞淋巴瘤患者的皮肤病变（7.7%）以及其它（23%）。关节炎痛、光化性角化病、热烧伤患者皮肤焦痂的去除、结节性硬化症相关的面部血管纤维瘤、大疱性表皮松解症、传染性软疣等适应症均各有1款产品。 2.3 药物类型分析 在这些局部皮肤用凝胶剂中，药物类型以小分子药物居多，包括贝沙罗汀、克林霉素磷酸酯、壬二酸、甲硝唑、氨苯砜（2款）、特比萘芬、阿达帕林、维A酸、双氯芬酸钠，盐酸萘替芬、盐酸氮芥、酒石酸溴莫尼定、盐酸5-氨基酮戊酸、西罗莫司。此外还包括三款具有特殊结构或组成的药物（anacaulase-bcdb、桦木三萜、贝达西美钠），其中anacaulase-bcdb是一种从菠萝植物的茎中提取的蛋白水解酶混合物，富含多种具有生物活性的蛋白质和糖类，通过无菌过滤和冷冻干燥技术制成；桦木三萜是从桦树的树皮中提取的植物药（botanical drug）, 是一种由五环三萜类化合物组成的混合物；贝达西美钠结构复杂，是一种包含多个硅氧烷和硅酸根的共聚物，这些部分通过特定的比例和方式连接在一起，可以释放一氧化氮从而发挥治疗作用。 这些产品中还包含4种固定剂量组合复方药物，即过氧苯甲酰+克林霉素磷酸酯（3款）、克林霉素磷酸酯+维A酸（2款）、阿达帕林+过氧苯甲酰（2款）、阿达帕林+过氧苯甲酰+克林霉素磷酸酯（1款），均用于治疗寻常痤疮。这些组合通过药物间的协同作用可以更好地发挥治作用。 来源：药事纵横 投稿/内容沟通：华籍美人（Ww_150525） 近期精华文章