Lopinavir

Receipt of award notice for second $1.0 million tranche of NIAID funding brings total NIH funding award for DARE-HPV to $2.0 million Funding award milestone follows Daré's announcement last week of the initiation of its Phase 2 clinical study of DARE-HPV — representing the first time women with persistent high-risk HPV infection may have access to this pharmacologic treatment as part of a clinical trial DARE-HPV targets high-risk HPV infection, the cause of virtually all cervical cancer cases in the U.S., for which there are currently no FDA-approved pharmacologic treatments Award reflects Daré's strategy of leveraging non-dilutive government funding, including both NIH grants and ARPA-H contract support for DARE-HPV, to advance a differentiated pipeline addressing some of the most persistent unmet needs in women's health SAN DIEGO, May 26, 2026 (GLOBE NEWSWIRE) -- Daré Bioscience, Inc. (NASDAQ: DARE) , a purpose-driven health biotech company solely focused on closing the gap in women's health between promising science and real-world solutions, today announced receipt of a Notice of Award from the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), obligating the second and final tranche of $1.0 million under the previously announced up to $2.0 million NIAID grant award for DARE-HPV, Daré's investigational treatment for persistent high-risk human papillomavirus (HPV) infection. The total amount of the award across the project period, which commenced in late 2024, is $2.0 million. This award (Award Number 5R44AI188623-02) was issued under the Small Business Innovation Research (SBIR) program in support of the project titled "A first-in-class product for the clearance of high-risk human papillomaviruses," with Andrea Ries Thurman, MD, Medical Director of Daré, serving as Project Director. The receipt of this award notice follows Daré's announcement on May 18, 2026 of the initiation of its Phase 2 clinical study of DARE-HPV, a significant clinical development milestone that marks the first time women with persistent high-risk HPV infection may have access to this pharmacologic treatment as part of a clinical trial. The Phase 2 study is a randomized, placebo-controlled, double-blind trial designed to evaluate the safety and antiviral activity of DARE-HPV in approximately 100 women with confirmed persistent high-risk HPV infection over an up to 21-day course of daily treatment, with topline data expected in 2027. "The NIH's continued commitment to DARE-HPV is a powerful validation of the unmet need driving this program," said Sabrina Martucci Johnson, President and CEO of Daré Bioscience. "An estimated 6 million women in the United States each year experience a high-risk HPV infection and have no FDA-approved pharmacologic option. They are told to wait and watch as the virus either clears on its own or, in far too many cases, progresses to precancerous or cancerous disease. Last week, we initiated our Phase 2 study to advance our potential alternative to that 'watchful waiting' paradigm. The NIAID funding award we are announcing today will help sustain the non-clinical and translational work that underpins this program, together with our ARPA-H-funded contract that supports the Phase 2 study. Daré was built to pursue exactly these kinds of high-impact, underserved opportunities, and we are grateful to NIH, ARPA-H, our clinical investigators, and the women participating in the Phase 2 study for helping us do just that." About the DARE-HPV NIAID Award This Notice of Award (Award Number 5R44AI188623-02) obligates $1.0 million for the second project year budget period from December 1, 2025 through November 30, 2026. The total federal award across the project period, which commenced December 17, 2024, is $2.0 million. The NIAID grant supports non-clinical activities to advance the development of DARE-HPV. The project is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R44AI188623. The content of this press release is solely the responsibility of Daré Bioscience, Inc. and does not necessarily represent the official views of the National Institutes of Health. About DARE-HPV DARE-HPV is an investigational, proprietary fixed-dose formulation of lopinavir and ritonavir in a soft gel vaginal insert being developed as a potential non-surgical, localized, self-administered treatment for persistent high-risk HPV infection. Lopinavir and ritonavir are protease inhibitors with established antiviral activity. HPV infection is the underlying cause of virtually all cervical cancer cases in the United States. An estimated six million women per year in the United States experience high-risk HPV infection, for which there are currently no FDA-approved pharmacologic treatments. If clinically successful and approved, DARE-HPV could be the first FDA-approved pharmacologic treatment for HPV infection. DARE-HPV development is supported by an up to $10 million contract funded by ARPA-H (Advanced Research Projects Agency for Health), as well as the NIAID grant award described herein. Daré's Investigational New Drug (IND) application for DARE-HPV was cleared by the FDA in February 2026, and Daré initiated its Phase 2 clinical study (ClinicalTrials.gov ID: NCT07601074) in May 2026. About the National Institute of Allergy and Infectious Diseases (NIAID) NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website at About Daré Bioscience Daré Bioscience is a purpose-driven health biotech company solely focused on closing the gap in women’s health between promising science and real-world solutions. Every innovation Daré advances is based in advanced science and backed by rigorous, peer-reviewed research. From contraception to menopause, pelvic pain to fertility, vaginal health to infectious disease, Daré is working to close critical gaps in care using science that serves her needs. For decades, women have been told to “wait it out” or “live with it,” while innovations that could improve their quality of life languish in the regulatory or funding pipeline. With growing awareness around menopause, sexual health, and vaginal health, the conversation is shifting. However, access to real, evidence-based solutions continues to lag. Daré was founded to change that. As a female-led health biotech company, Daré is accelerating the development of credible, science-based solutions that meet the high standards of clinical rigor – randomized, controlled trials; validated endpoints; peer-reviewed publications; and current Good Manufacturing Practice (cGMP) requirements. To learn more about Daré’s mission to deliver differentiated therapies for women and its innovation pipeline, please visit . Daré may announce material information about its finances, products and product candidates, clinical trials and other matters using the Investors section of its website ( ), SEC filings, press releases, public conference calls and webcasts, and social media channels. The information Daré posts on its investor relations website or through social media channels may be deemed to be material information. Daré encourages investors, the media, and others interested in the company to review the information Daré posts in the Investors section of its website, to follow Daré Bioscience, Inc. on LinkedIn, and to follow these X (formerly Twitter) accounts: @SabrinaDareCEO and @DareBioscience. Any updates to the list of social media channels the company may use to communicate information will be posted in the Investors section of Daré’s website. Forward-Looking Statements Daré cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “plan,” “potential,” “prepare,” “aim,” “should,” “would,” “target,” “advance,” “positioned,” or the negative version of these words and similar expressions. In this press release, forward-looking statements include, but are not limited to, statements relating to the significance of the NIH award to Daré and the DARE-HPV program, DARE-HPV’s potential as a safe and effective treatment for clearance of high-risk HPV infection, DARE-HPV’s potential to be the first FDA-approved pharmacologic treatment for high-risk HPV infection, the conduct and completion of the Phase 2 clinical study of DARE-HPV and the timing of topline data from the study, the anticipated benefits of DARE-HPV, including its potential to reduce the incidence of cervical cancer in the U.S., the potential for DARE-HPV to redefine the treatment paradigm for HPV infection, Daré’s expectation of receipt of additional funding under its ARPA-H award, and the potential market opportunity for DARE-HPV, if approved. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Daré’s actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including, without limitation, risks and uncertainties related to: failure or delay in conducting or completing a clinical trial and the inherent uncertainty of outcomes of clinical trials; the risk that positive findings in early clinical and/or nonclinical studies of a product candidate may not be predictive of success in subsequent clinical and/or nonclinical studies of that candidate; Daré’s ability to develop, obtain FDA or foreign regulatory approval for, and commercialize its product candidates and to do so on communicated timelines; the risk that Daré’s product candidates may fail to demonstrate acceptable safety and tolerability or sufficient efficacy in clinical trials; Daré’s ability to design and conduct successful clinical trials, to enroll a sufficient number of patients, to meet established clinical endpoints, to avoid undesirable side effects and other safety concerns, and to demonstrate sufficient safety and efficacy of its product candidates; Daré’s dependence on third parties to conduct clinical trials and manufacture and supply clinical trial material and commercial product; the potential that a product candidate in clinical development may never advance into or through a pivotal clinical study or obtain FDA or foreign regulatory approval; the risk that the FDA, other regulatory authorities, members of the scientific or medical communities or investors may not accept or agree with Daré’s interpretation of or conclusions regarding data from clinical studies of its product candidates; the risk that development of a product candidate requires more clinical or nonclinical studies than Daré anticipates, or that the duration of a study or number of study subjects must be significantly greater than anticipated; Daré’s ability to achieve the milestones required for it to receive additional payments under its ARPA-H award; the potential for significant delays in disbursement of government awarded funds or termination of an award before Daré’s receipt of the full amount of obligated funds; Daré’s ability to raise additional capital when and as needed to execute its business strategy and continue as a going concern; Daré’s dependence on grants and other financial awards from governmental entities and a private foundation; Daré’s ability to maintain compliance with Nasdaq’s continued listing requirements and continue to have its common stock listed on The Nasdaq Capital Market; the effects of macroeconomic conditions, geopolitical events, and major changes and disruptions in U.S. government policies and operations on Daré’s ability to raise additional capital or on Daré’s operations, financial results and condition, and ability to achieve current plans and objectives; the risk that the current regulatory pathway known as the FDA’s 505(b)(2) pathway for drug product approval in the U.S. is not available for a product candidate as Daré anticipates; the risk that developments by competitors make Daré’s product or product candidates less competitive or obsolete; difficulties establishing and sustaining relationships with development and/or commercial collaborators; failure of Daré’s products or product candidates, if approved, to gain market acceptance or obtain adequate coverage, pricing and reimbursement from third-party payors; Daré’s ability to retain its licensed rights to develop and commercialize a product or product candidate; Daré’s ability to satisfy the monetary obligations and other requirements in connection with its exclusive, in-license agreements covering the critical patents and related intellectual property related to its products and product candidates; Daré’s ability to adequately protect or enforce its, or its licensor’s, intellectual property rights; the lack of patent protection for the active ingredients in certain of Daré’s product candidates which could expose its products to competition from other formulations using the same active ingredients; product liability claims; governmental investigations or actions relating to Daré’s products or product candidates or the business activities of Daré, its commercial collaborators or other third parties on which Daré relies; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; and cybersecurity incidents or similar events that compromise Daré’s technology systems and/or significantly disrupt Daré’s business or those of third parties on which Daré relies. Daré’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. For a detailed description of Daré’s risks and uncertainties, you are encouraged to review its documents filed with the U.S. Securities and Exchange Commission, including Daré’s recent filings on Form 8-K, Form 10-K and Form 10-Q. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Daré undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Contacts: Daré Bioscience Investor Relations innovations@darebioscience.com Source: Daré Bioscience, Inc.

1799年12月14日清晨，乔治·华盛顿离世前，现代医学并非束手无策，反而用尽了当时所有医疗手段。多位医生反复为他放血，使用催吐剂、灌肠剂与发泡疗法，穷尽18世纪上流医学界最主流的积极治疗手段。当晚，华盛顿因疑似急性细菌性会厌炎，加之失血过多不幸离世。这场悲剧的根源，从来不是医生无所作为，而是他们在毫无实证依据的情况下，过度施治、盲目自信。 放血疗法能够沿用数千年，究其根源，是它契合了当时主流的疾病诊疗理论。这套疗法逻辑通顺、直观可见、极具权威性，诊疗场面也极具仪式感，形成了一套固化的诊疗思维：疾病源于体内气血过剩、阴阳失衡、气血瘀滞，而医者只需切开血管，便能调和身体秩序。直至皮埃尔-夏尔-亚历山大·路易等临床医师开始统计诊疗结局、开展对照研究、验证放血疗法是否真能改善患者预后，这套古老疗法才逐渐丧失科学说服力。 REMAP-CAP研究中的伊维菌素临床试验，正延续了这段医疗史的前车之鉴。将其与放血疗法类比，并非指代伊维菌素存在直接毒性或疗法野蛮粗暴——该试验采用临床常规剂量的伊维菌素，并未引发严重不良反应。二者真正的共性，更为深远且暗藏隐患：医疗行业在公共卫生危机期间，极易将逻辑合理性、主观诊疗信心、积极干预行为，等同于能够切实惠及患者的临床实证。 这类认知误区有着相似的特征：药理作用理论依据单薄、大众认可度远超临床数据、权威人士笃定其疗效、临床普及速度远早于完整实证落地。因此，REMAP-CAP试验的意义，早已超越验证伊维菌素疗效本身，更是一场现代医学“及时叫停无效疗法”的实践探索。 这一研究极具现实意义，新冠疫情绝非单纯的科学研究难题。全球范围内新冠确诊死亡病例超700万，疫情期间临床医生始终身处恐惧迷茫、舆论审视、药物紧缺的高压环境下艰难决策。部分治疗方案凭借随机对照试验证实有效后迅速普及；还有部分疗法仅凭价格低廉、易获取、理论可行、贴合大众心理诉求，或是经公众人物推崇，在缺乏充足临床数据支撑的情况下投入临床应用，伊维菌素便是此类疗法最典型的代表。 此次临床试验带来的核心启示，绝非仅证实伊维菌素无法为住院新冠患者带来治疗获益，更深层次的意义在于：淘汰无效疗法，与推广有效疗法同等重要。医学的进步，不只在于研发全新治疗手段，更在于学会理性取舍，主动摒弃错误的诊疗方式。放血疗法：盲目施治的医疗执念 放血疗法绝非小众诊疗手段，而是近代以前主流的核心治疗方式，盛行多国、流传数百年，内科医师、外科医师乃至理发外科医师（中世纪欧洲职业，剃头匠兼职做手术、拔牙、放血、治外伤，是早期民间基层医者）均广泛使用。19世纪欧洲医疗行业愈发规范化专业化之际，放血疗法的应用反而达到顶峰。 由此可见，该疗法长久盛行，并非源于医者愚昧无知，而是一套逻辑自洽却背离医学真相的诊疗体系，极具迷惑性。 在信奉体液学说的医者眼中，放血疗法合乎诊疗逻辑。发热、炎症、气血壅滞、情绪躁动等病症，在当时看来都需要通过排泄体内多余体液来调理。这种治疗方式主动性强、适配不同患者、诊疗过程直观，患者能切身感受到干预行为，家属也能亲眼所见，医者也切实采取了诊疗措施。在疾病带来的负面情绪氛围中，这种看得见的干预行为，本身就具备心理安抚作用。 这也是无效疗法难以彻底取缔的核心原因：这类疗法满足了循证医学难以兼顾的心理需求——医者渴望有所作为、患者渴求治愈希望、大众期盼直观诊疗手段，而非直面医学无法确诊、无法治愈的现实困境。放血疗法赋予了医疗固定的干预仪式，而新冠疫情期间诸多跨界复用的药物，也陷入了同样的误区。 放血疗法走向没落，并非诞生了更完善的疾病理论，而是源于临床数据统计。皮埃尔-夏尔-亚历山大·路易运用数据统计分析法，针对肺炎等疾病展开研究，对比早期放血与晚期放血患者的预后差异。以现代医学标准来看，他的研究存在诸多漏洞，但其研究理念极具颠覆性：临床诊疗的权威性，必须依靠大批量患者的实际预后数据来佐证。 这也正是REMAP-CAP试验传承的医学精神。研究的核心不在于论证伊维菌素的药理作用是否存在理论依据，而在于验证使用伊维菌素的患者，预后是否优于未使用者。摒弃主观理论猜想，依托对照试验验证疗效，是医学发展史上里程碑式的进步。主观笃定，素来与实证相去甚远 伊维菌素并非冷门药物，作为广泛应用的抗寄生虫药，早已列入世界卫生组织基本药物清单，临床应用数十年，适应症明确。大众对这款药物的熟悉度，为其疫情期间的推广埋下伏笔。 这款药物口服便捷、价格低廉、全球易得，且用药安全数据成熟，本是疫情中极具潜力的备选治疗药物。倘若其真能对抗新冠病毒，必将为全球公共卫生事业带来巨大变革。 但主观用药期许，终究无法等同于药理临床实效。疫情期间各界对伊维菌素疗效的笃定程度，始终与临床实证的完善程度严重不符。REMAP-CAP试验补充附录中明确记载：伊维菌素一度被奉为“新冠神药”，在高、中、低收入国家跳过临床试验广泛投入使用，各类公益组织、临床诊疗指南纷纷推崇，甚至登上政治议事议程，各类新冠患者用药后痊愈的舆论宣传层出不穷。受大众用药热潮影响，部分地区还出现医药游说、医疗机构强制采购，甚至药物走私等乱象。 伊维菌素从一项待验证的药物复用猜想，演变成全民追捧的社会风潮，二者有着本质区别。尚未普及的无效药物猜想可自然搁置，一旦大范围融入常规临床诊疗，便会演变为整个医疗体系的治理难题。 疫情期间，美国门诊伊维菌素处方量暴涨：疫情前每周平均处方量约3600张，2021年1月8日当周峰值飙升至3.9万张。美国疾控中心随后发出预警，滥用伊维菌素、误用兽用伊维菌素制剂的情况频发，药物中毒求助案例大幅增加。后续全国调研显示，擅自使用伊维菌素、羟氯喹治疗新冠的人群，大多轻信不实医疗言论，对医护人员与科研人员缺乏信任，极易盲从阴谋论，信息获取渠道也相对片面。 唯有结合这一社会背景，才能读懂REMAP-CAP试验的深层价值。该试验绝非单纯的药物疗效验证，更是一场医学实证回归之战——在大众主观认知远超临床实证的大环境下，重塑临床诊疗以数据为核心的准则。放血疗法依托传统体液学说盛行，伊维菌素依托网络舆论风靡，二者共性在于：尚未经临床证实疗效，便已获得广泛社会认可度。 图2：放血疗法与新冠伊维菌素疗法的兴起及淘汰历程药理推演，终究难成临床预判 伊维菌素用于新冠治疗的研究起源，和多数跨界复用药物一致，最初源于实验室体外实验研究。卡利团队研究证实，伊维菌素可在体外抑制新冠病毒复制。鉴于该药物已获批上市、普及度高，这一实验结论迅速引发全民关注。 此外，还有研究提出其具备抗炎作用，动物实验也得出相关利好结论，从抗病毒、调节机体免疫两大层面，构建起看似合理的药理作用猜想。 但从体外细胞实验落地到人体临床应用，存在巨大的鸿沟，有效药物浓度是核心阻碍。疫情初期，施密特团队便提出观点：临床常规剂量的伊维菌素，无法达到体外实验中抑制新冠病毒所需的药物浓度，常规剂量下难以实现临床疗效。REMAP-CAP试验补充附录也印证了这一观点：目前学界提出的伊维菌素抗新冠作用机制繁多，但尚无任何一种机制具备确切临床疗效，且部分起效所需药物浓度，根本无法在人体临床用药中实现。 就连伊维菌素原研药企默沙东，也在2021年2月公开表态：综合现有临床前研究数据，未发现伊维菌素具备治疗新冠的科学依据，无确凿临床证据证实其疗效，绝大多数相关研究也缺乏完善的用药安全数据。美国食品药品监督管理局也明确声明，未批准伊维菌素用于新冠预防与治疗，现有临床试验数据均无法证实其对人体新冠感染具备治疗效果。 以上结论，并非否定开展伊维菌素新冠临床试验的必要性，而是坚决反对未经验证便盲目笃定疗效。药理层面具备可行性，是开展临床试验的合理理由，却绝不能替代临床试验本身。当年放血疗法同样具备完整的理论机制，最终被淘汰，只因这套理论体系，始终无法挽救患者生命。假说纵然立论薄弱，试验仍需严谨求证 不少人认为，伊维菌素药理依据薄弱、药代动力学存在缺陷、早期临床数据可信度低，本就无需投入精力研究。但这一观点在药物已经大范围投入临床后便不再成立。 当一款药物跳过实证直接普及，研究核心便从“这款药物是否有效”，转变为“证实无效后，该如何叫停临床应用”，这也是REMAP-CAP试验具备重要伦理价值的核心原因。 研究人员在试验附录中明确表示：无论是临床前药理研究，还是早期临床数据，均无法支撑大众对伊维菌素抗新冠疗效的狂热追捧，但鉴于该药物已在全球临床大范围滥用，开展高质量随机对照试验迫在眉睫，这也是此项研究的核心初衷。 即便一款药物具备临床获益的概率极低，一旦流入常规诊疗流程，就必须开展严谨的临床试验验证疗效。缺乏随机对照试验数据支撑，临床诊疗只能依靠个案案例、主观臆断与行业权威言论；唯有依托实证数据，才能顺利淘汰无效疗法。 能够助力临床摒弃无效用药方案的临床试验，绝非失败的研究。 2022年起，越来越多门诊临床试验证实伊维菌素无新冠治疗价值。考克兰系统综述明确指出，无任何可靠证据证实伊维菌素可治疗新冠、预防新冠病毒感染；洛佩斯-梅迪纳团队研究证实，伊维菌素无法缩短轻症新冠患者症状消退时长；TOGETHER临床试验证实，早期使用伊维菌素，无法降低门诊新冠患者住院率与急诊留观时长。除此之外，COVID-OUT、I-TECH、ACTIV-6等多项临床试验，即便提升用药剂量、延长用药疗程，依旧未能证实其具备显著临床疗效。 世界卫生组织现行诊疗指南也态度明确：除正规临床试验外，严禁将伊维菌素用于新冠临床治疗。 即便诸多门诊研究否定其疗效，仍留有关键临床空白：伊维菌素对住院新冠患者、危重症新冠患者是否有效？在高价生物制剂、新型抗病毒药物难以普及的地区，这类廉价易得的药物是否存在临床价值？这一问题具备极强的临床意义与全球公共卫生研究价值，绝非多余研究。 放血疗法的淘汰历程同样印证这一道理：它并非在穷尽所有病症、所有施治剂量、所有适用人群的对照试验后才被摒弃，而是整体诊疗价值被彻底推翻后，逐步退出医疗舞台。医学研究无需穷尽所有可能性，只需证实临床常规应用无价值，便足以叫停普及使用。REMAP-CAP研究究竟做了什么？ REMAP-CAP并非依附常规诊疗开展的传统双臂对照试验，而是一项国际性、嵌入式、多维度、适应性平台临床试验，主要针对重症肺炎（含新冠呼吸道重症感染）患者，同步开展多项治疗方案疗效研究。 该试验设计优势显著：可对患者进行多维度随机分组，运用贝叶斯统计模型，还能依托不断积累的临床数据，动态调整试验分组比例。伊维菌素试验分组详情 研究时间：2021年6月11日—2022年9月9日 研究地区：巴基斯坦、印度、爱尔兰 研究对象：确诊或疑似新冠感染的成年住院患者 人群划分：ICU内需呼吸、循环器官支持治疗者划为危重症患者，其余住院患者划为非危重症患者 干预方案：试验组口服伊维菌素，每日剂量0.2毫克/千克，单日最大剂量24毫克，最长连续用药5天，或直至患者出院；对照组不使用伊维菌素，其余诊疗方案严格遵循当地临床常规标准 主要研究终点：无器官支持治疗天数（综合分级评估指标，死亡为最差预后结果；存活患者统计21天内无需呼吸、循环器官支持治疗的存活时长） 简单来说，该指标核心评估两点：患者是否存活，以及患者多久能够脱离重症生命支持治疗。 这一评估指标高度适配重症医学临床研究。单一死亡率评估过于片面：依靠长期呼吸机、血管活性药物、肾脏替代治疗维持生命，长期滞留ICU的存活患者，与快速康复脱离重症干预的患者，预后质量天差地别。而无器官支持治疗天数，既能评估生存率，也能直观反映重症疾病给患者带来的身心与医疗负担。 十九世纪路易统计肺炎患者预后否定放血疗法，如今REMAP-CAP试验统计无器官支持治疗天数验证伊维菌素疗效，二者研究手段不同，坚守的医学准则高度一致：摒弃主观理论猜想，以患者真实预后数据为唯一评判标准。临床试验核心研究结果 此次试验最终纳入150例可统计主要研究终点数据的患者，其中危重症患者61例，非危重症患者89例。受此前多项门诊临床试验证实伊维菌素无效影响，试验招募患者数量持续锐减，最终因实际开展难度过大提前终止，并非达到试验预设的贝叶斯统计无效终止标准。核心数据结果 危重症患者：两组患者中位无器官支持治疗天数均为-1，死亡为最主要预后结局；伊维菌素组住院生存率35.1%，对照组37.5%，疗效对比无统计学差异，无任何数据证实伊维菌素可提升危重症患者生存率、加快康复速度。 非危重症患者：伊维菌素组住院出院率84.1%，对照组77.8%，数值上略占优势，但数据校正后误差范围极大，疗效优势可信度极低，无法作为临床常规用药依据，极易引发片面解读。 次要研究终点数据同样未能证实伊维菌素具备临床获益：该药物无法缩短ICU入住时长、住院时长，无法提升患者90天生存率，也无法降低患者进展为有创机械通气、体外膜肺氧合支持治疗乃至死亡的风险，更无法改善患者发病14天临床病情分级。 用药安全性层面，两组均未出现严重药物不良反应，证实此次临床常规剂量用药安全性良好，但用药安全绝不等于具备临床疗效，无法作为常规临床用药的依据。 当年医者依靠个案存活案例佐证放血疗法有效，如今大众也极易将用药后痊愈的个案，错误归因为药物起效，混淆“先后关系”与“因果关系”。而REMAP-CAP试验彻底规避这一误区，研究核心从不局限于“部分患者用药后康复”，而是验证“用药人群康复概率是否显著高于未用药人群”，这也是主观诊疗经验与严谨临床科学的本质区别。试验结论解读：非有效、亦未彻底证实无效 该试验最易被误解的结论为：伊维菌素既未证实临床有效，也未彻底判定完全无效，但基本可确定其无法改善患者无器官支持治疗天数与住院生存率。 这一表述并非模棱两可，而是贝叶斯临床试验严谨的客观表述。该试验提前设定明确判定标准：疗效判定标准为疗效优势后验概率超99%；无效判定标准为疗效提升概率低于95%。此次试验两项判定标准均未达成，并非代表临床应用无任何影响，只是尚未达到平台试验预设判定阈值，便因现实因素提前终止。 客观理性的解读应为：该试验无法彻底排除所有用药剂量、用药时机、感染毒株亚型、特定人群下伊维菌素存在微弱疗效的可能性，但足以证实此次试验所用用药方案，对住院危重症、非危重症新冠患者无显著临床获益，仅凭现有数据，完全足以否定其住院临床常规应用的合理性。 医学领域淘汰无效疗法向来循序渐进，放血疗法并非仅凭一项试验便彻底消亡，而是历经层层数据验证、多方质疑、预后对比后，逐步退出主流诊疗体系，伊维菌素的临床应用取缔也应遵循这一准则。叫停一款药物无需做到绝对定论，只需掌握充足实证，证实持续临床应用缺乏医学依据即可。试验的全球公共卫生价值 此次试验一大核心亮点，同时也是数据解读难点在于：96%的受试患者来自巴基斯坦，3%来自印度。不同于以往低收入国家单纯沿用欧美临床研究结论，该试验直接在药物易得、性价比高、临床需求迫切的地区开展研究，研究结论更贴合当地临床实际。 新冠疫情期间，全球医疗资源分配不均问题愈发凸显，高价生物制剂、新型特效抗病毒药物在多数欠发达地区难以普及。在此背景下，大众追捧伊维菌素这类廉价仿制药，从用药可及性层面而言情有可原。 人们渴望平价抗疫药物无可厚非，错误之处在于：尚未证实疗效，便大肆推广普及。 试验基线诊疗数据也印证了全球重症诊疗水平的差距：此次受试患者中，92%入院48小时内使用糖皮质激素，78%使用瑞德西韦，仅5%患者使用托珠单抗、萨利单抗等高价免疫调节药物，核心受限因素便是药物价格与供应不足。受试人群整体死亡率偏高，危重症患者死亡率达64%，非危重症患者死亡率达19%。 这一现状也提醒医学界：不同地区新冠患者入院诊疗时机、重症器官支持治疗启动标准、有效免疫药物普及程度截然不同，各地临床常规诊疗方案也存在巨大差异。 因此，类比放血疗法评判伊维菌素时需保持理性：资源匮乏地区临床医师追捧此类无实证药物，并非缺乏辨别能力，而是身处全球临床实证滞后、本地治疗手段匮乏的双重困境。 平价抗疫药物值得全力开展严谨临床试验，一旦证实有效，便能最大限度惠及医疗资源紧缺地区人群。而REMAP-CAP试验最珍贵的价值，便是直面欠发达地区的临床诊疗困境，就地开展实证研究，而非照搬发达国家研究结论。有效疗法推广与无效疗法取缔是一体两面 新冠疫情期间，医学领域既见证了有效疗法快速普及，也完成了多项无效疗法的临床淘汰。RECOVERY试验证实地塞米松可降低吸氧、有创通气新冠住院患者28天死亡率后，迅速纳入全球临床常规诊疗；REMAP-CAP试验证实白介素6受体拮抗剂可改善危重症新冠患者预后后，托珠单抗、萨利单抗也正式纳入危重症新冠核心治疗方案，这都是依托实证快速推广有效疗法的典型案例。 反之，REMAP-CAP试验也曾证实，洛匹那韦-利托那韦、羟氯喹及其联合用药，相较于常规诊疗，反而会加重危重症新冠患者病情。取缔无效疗法的临床价值，丝毫不亚于推广全新有效疗法。 临床试验的价值，从来不是筛选出越多可用药物越好，而是最大限度守护患者预后与生命健康，伊维菌素的临床研究便属于后者。 主动取缔无效临床干预手段，绝非消极无为的诊疗态度，更不是放弃救治患者，而是主动摒弃依靠大众期许、临床习惯、舆论推崇、恐慌心理、行业固有思维维系，却无任何确切疗效的诊疗方式。 放血疗法的没落，便是近代医学尚未提出“无效疗法取缔”概念时，最早的临床淘汰实践。医者放下放血针，并非日渐冷漠，而是临床诊疗开始以患者真实预后数据为核心准则。这一医学理念，也让我们明白：阴性结果的临床试验，同样能为临床诊疗带来巨大正向价值。 医疗领域低价值诊疗行为的危害早已形成明确研究定论：这类干预手段不仅会带来直接药物不良反应，还会加重患者心理负担、挤占优质医疗资源、造成医疗经费浪费，甚至引发一系列后续过度诊疗行为。如今，主动摒弃低价值临床诊疗手段，已成为全球医疗体系亟待解决的难题，绝非单纯依靠传播临床知识便能实现。 尤其当临床诊疗习惯、行业固有认知、舆论风向与实证结论相悖时，依托循证医学取缔无效疗法更是举步维艰，这也正是伊维菌素相关临床试验意义重大的根源。 滥用无疗效新冠药物的危害，远不止药物毒副作用：会挤占有效治疗手段的应用空间、延误患者最佳正规治疗时机、激化医患沟通矛盾、消解大众对正规医疗的信任、浪费公共医疗资源，阻碍新型有效诊疗方案的研究与推广。 美国医保机构统计数据显示，疫情期间大量医保资金用于无疗效的伊维菌素新冠处方，造成巨额不必要医疗开支，足以印证：即便低价药物，大规模无意义滥用，依旧会造成沉重的医疗资源损耗。 试验利弊客观评析客观局限性 试验样本量偏小，研究数据误差范围较大 试验为开放标签试验，无法彻底规避主观诊疗偏见 试验因实际招募难度提前终止，未达成预设统计学无效判定标准 采用临床常规实用剂量，未尝试更高用药剂量 受试人群绝大多数为南亚人群，地域人群覆盖面有限 基线阶段危重症患者接受有创通气治疗比例偏低，与临床真实危重症诊疗场景存在偏差 以上短板均客观存在，但依旧无法支撑伊维菌素临床常规应用的合理性。 针对用药剂量的争议最为普遍：不少观点认为提升用药剂量或许能实现疗效。但疫情初期药代动力学研究早已证实，人体可耐受的安全用药浓度，根本无法达到体外实验抑制病毒所需浓度；后续多项高剂量、长疗程伊维菌素临床试验，依旧未能证实其具备稳定临床疗效。一味归咎于用药剂量不足，早已脱离客观医学研究范畴。 样本量不足导致数据偏差属实，而数据双向偏差也印证了核心观点：我们无法绝对断言伊维菌素在任何新冠感染场景、任何人群中均无丝毫作用，但更不能凭借不稳定的小幅利好数据，盲目推崇普及用药。结合此次试验与全球多项随机对照试验结论、权威诊疗指南，足以证实其无临床常规应用价值。 人群地域局限性反而提升了试验实用价值：受试人群集中在医疗资源有限、用药性价比优先级更高的南亚地区，恰恰在这类最期盼平价抗疫药物的地区证实无效，研究结论的现实指导意义更为重大。 将伊维菌素与放血疗法类比或许略显严苛，常规剂量伊维菌素不存在放血疗法那般极具创伤性的伤害。但二者核心误区完全一致：仅凭理论可行、干预直观、大众推崇、贴合心理期许便盲目普及，忽略最核心的患者预后数据。试验核心价值 REMAP-CAP伊维菌素临床试验虽存在瑕疵，却是疫情期间不可或缺的重要研究。 直面社会大众早已普及的用药乱象，用严谨试验解答临床刚需难题 聚焦医疗资源紧缺地区，针对性开展平价药物疗效验证 依托适配疫情突发研究需求的平台试验设计开展研究 同步纳入危重症与普通住院患者，覆盖全层级住院人群 选用兼顾生存率与康复质量的科学评估指标 如实公布研究数据偏差，拒绝片面解读试验结论 最为关键的是，此项研究彻底打破了伊维菌素依靠舆论热度维系的用药认知误区。医学领域中，叫停无效疗法远比推广全新疗法更加艰难：推广新疗法自带希望与新意，极易获得大众认可；而叫停无效疗法，不仅要打破大众固有期许，还要直面医患沟通的压力，告知大众追捧的治疗方案并无实际疗效。 此类临床试验，能够让临床诊疗决策脱离个人主观偏好，依托客观概率数据制定方案，这也正是当年路易数据统计分析法革新放血疗法诊疗认知的核心意义。自此，临床诊疗再也不能单纯依靠传统理论、行业权威、治愈个案下定论，必须直面大批量患者的真实诊疗结局。临床实践落地建议 除正规获批临床试验外，严禁将伊维菌素常规用于成人新冠住院患者（含危重症患者）治疗。这一建议并非排斥平价基层用药，也并非无视全球医疗资源不均的现状，而是依托REMAP-CAP试验阴性结论、全球多项随机对照试验一致阴性结果、前期药理研究隐患以及各国药监机构、权威诊疗指南共同得出的严谨结论。 各级医疗机构需主动落实无效疗法取缔工作：将伊维菌素剔除新冠常规用药清单，同步修订本地临床诊疗方案；指导临床医师妥善做好医患沟通工作，理性劝导患者摒弃盲目用药观念；杜绝“以防万一”式的随意开具处方行为。 看似温和无害的低价值药物，取缔难度往往最大。但这类药物即便无明显毒副作用，依旧会挤占临床诊疗精力、扰乱诊疗优先级、耽误正规有效治疗。 纵观医学发展史，医学进步不仅依托抗生素、麻醉技术、无菌操作、重症监护等全新医疗技术的诞生，更源于主动摒弃催吐疗法、发泡疗法、盲目放血等主观臆断式诊疗手段。 现代医学的进步往往润物无声：悄然剔除无效用药清单、修订临床诊疗指南、坦诚告知患者诊疗真相、临床医师主动放弃无获益的安抚性用药。 未来一旦爆发新一轮公共卫生疫情，依旧会重现相似的用药乱象：具备理论可行性、低价易得、贴合大众心理诉求的药物会快速走红，尚未完善的初步研究数据被大肆炒作，公众舆论先于科研人员笃定药物疗效。 应对此类乱象，无需消极质疑全盘否定，只需秉持三大原则：快速开展临床试验、客观解读研究数据、积极推广证实有效的诊疗方案、果断叫停无实证的无效干预手段。总结 切勿将REMAP-CAP伊维菌素临床试验视作舆论对立的附属产物，它更是一场现代医学“理性叫停无效疗法”的经典研究范本。该研究针对一款理论依据薄弱、却凭借强大社会舆论热度大范围普及的药物开展验证，最终证实：无论危重症还是普通新冠住院患者，使用伊维菌素均无法显著提升生存率、加快脱离重症器官支持治疗。 此项试验虽未彻底穷尽所有用药可能性，但已然彻底否决其住院临床常规应用的医学价值。 放血疗法的没落警示医学界：将积极诊疗行为等同于临床疗效，是医疗行业最危险的认知误区；伊维菌素的临床研究历程印证，在舆论传播、政治导向、大众求生欲的助推下，这类认知误区依旧会以全新形式重现；而REMAP-CAP试验则树立了纠正误区的医学准则：立足大批量患者临床数据、对照分析真实预后、理性果断叫停无效诊疗。 这份研究成果意义深远。在重症医学领域，主动舍弃无效诊疗干预，往往能够挽救更多生命。部分临床试验旨在研发全新治疗方案，而此类临床试验，旨在纠正医学界走入歧途的诊疗误区。 放血疗法最终退出历史舞台，并非医学诊疗愈发保守无为，而是临床诊疗彻底摆脱传统理论、诊疗仪式、行业权威与主观期许的束缚，真正以患者实际预后数据为核心准则。REMAP-CAP伊维菌素临床试验，正是延续这一严谨求真的医学传承——当临床数据最终战胜主观执念，仅凭理论猜想与大众追捧维系的无效疗法，终将彻底退出临床舞台。