Butorphanol Tartrate

Statistically significant lower "Drug Liking" for the 81mg and 162mg doses of oral nalbuphine vs. butorphanol covering our clinical dose range Company to host a conference call and webcast today at 5:00 p.m. ET NEW HAVEN, Conn., Dec. 3, 2024 /PRNewswire/ -- Trevi Therapeutics, Inc. (Nasdaq: TRVI), a clinical-stage biopharmaceutical company developing the investigational therapy Haduvio™ (oral nalbuphine ER) for the treatment of patients with chronic cough in idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC), today announced positive results from the human abuse potential (HAP) study of oral nalbuphine. The HAP study was a randomized, double-blind, double-dummy, active and placebo controlled five-way crossover study in recreational drug users. The study's primary endpoint was the peak effect (Emax) for "Drug Liking" ("at this moment"), assessed on a bi-polar, 100-point visual analog scale (VAS). The VAS scale for this endpoint ranges from strong disliking (0) – to neither like nor dislike (50) – to strong liking (100). Oral nalbuphine was analyzed across three different doses (ranging from a low dose to a supratherapeutic dose) for its "Drug Liking" compared to the active comparator, intravenous (IV) butorphanol, and placebo. Topline results demonstrated a statistically significant lower "Drug Liking" for the clinical doses of oral nalbuphine (81mg and 162mg) compared to 6mg IV butorphanol. The supratherapeutic dose of oral nalbuphine (486mg) was numerically lower than the 6mg IV butorphanol for "Drug Liking" but the results were not statistically significant. Primary Endpoint* *All analyses performed were on the Modified Completer Population, which was prespecified in the statistical analysis plan for the primary endpoint. Secondary Endpoints Secondary endpoints included pharmacodynamic markers and patient reported outcomes, which were generally consistent with the primary endpoint. No serious adverse events were reported in the study. "We're very pleased with our study results," said James Cassella, Ph.D., Chief Development Officer of Trevi Therapeutics. "The positive butorphanol drug liking effect versus placebo demonstrates the validity and robustness of our study design. Our clinical program has studied doses ranging from 27mg to 162mg and we believe these results are consistent with the known profile of nalbuphine. We look forward to reporting data from our two ongoing chronic cough studies in IPF and RCC, two conditions where patients continue to have a significant unmet need." Jack Henningfield, Ph.D., Vice President, Research, Health Policy and Abuse Liability at Pinney Associates added, "Nalbuphine is currently unscheduled in the U.S. and has been for several decades. It has remained unscheduled because of its years of experience with little evidence of diversion, abuse, or contribution to overdose deaths. This experience, coupled with these HAP results, continues to support the conclusion that nalbuphine extended-release has potential to address an important health need without the public safety risks posed by the opioids that are often prescribed for chronic cough." The results of the HAP study will be included in the 8-factor analysis of the abuse potential of nalbuphine for nalbuphine ER that would be submitted as part of any new drug application (NDA) submission to inform scheduling considerations. The Company will host a conference call and webcast to review the topline results today, December 3rd, at 5:00 p.m. ET. The live webcast, including audio and presentation slides, will be accessible at the time of the meeting and can be accessed here. To participate in the conference call by phone, please dial (877) 870 4263 (domestic) or (412) 317 0790 (international) and ask to join the Trevi Therapeutics call. No code is necessary for access. An archived replay of the webcast will also be available for 30 days on the Company's website following the event. About the Human Abuse Potential Study for Oral Nalbuphine The HAP study was conducted in two parts. The first part of the study characterized various IV butorphanol doses in order to select a dose to be studied as the comparator. The second part of the HAP study being reported in this release was a randomized, double-blind, double-dummy, active and placebo-controlled five-way crossover study. The U.S. Food and Drug Administration, or FDA, agreed to the comparator (butorphanol), comparator route of administration (IV to mimic intranasal exposure), comparator dose (6mg), and nalbuphine doses. This study compared the likeability of three doses of oral nalbuphine with 6mg of IV butorphanol using various drug-liking scales, including the primary endpoint, which measured the peak effect for "Drug Liking" assessed using a bi-polar visual analog scale. Safety and physiological measures, pharmacokinetic data, and abuse-related adverse events were also evaluated. About Trevi Therapeutics, Inc. Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing the investigational therapy Haduvio™ (oral nalbuphine extended-release) for the treatment of chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC). Haduvio acts on the cough reflex arc both centrally and peripherally as a kappa agonist and a mu antagonist (KAMA), which are opioid receptors that play a key role in controlling cough hypersensitivity. Nalbuphine is not currently scheduled by the U.S. Drug Enforcement Agency. Chronic cough is highly prevalent among approximately 140,000 IPF patients in the U.S., with up to 85% of IPF patients experiencing chronic cough. The impact of chronic cough is significant with some IPF patients coughing up to 1,500 times per day and may lead to worsening disease, a higher risk of progression, death, or need for lung transplant. Chronic cough also often leads to a decline in patients' social, physical, and psychological quality of life. There are no approved therapies for the treatment of chronic cough in IPF and current off-label treatment options provide minimal benefit to patients. Refractory chronic cough affects approximately 2-3 million adults in the U.S. and is caused by cough reflex hypersensitivity in both the central and peripheral nerves. It is highly disruptive and accompanied by a wide range of complications, ranging from urinary incontinence in females to sleep disruption and social embarrassment that causes significant social and economic burdens for patients and those around them. Haduvio is being developed for the treatment of moderate to severe RCC. There are also no approved therapies for RCC in the U.S. Trevi intends to propose Haduvio as the trade name for oral nalbuphine ER. Its safety and efficacy have not been evaluated by any regulatory authority. For more information, visit and follow Trevi on X (formerly Twitter) and LinkedIn. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding Trevi's business plans and objectives, including future plans or expectations for Haduvio and plans and timing with respect to clinical trials and clinical data, expectations regarding the abuse potential of Haduvio, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions. Risks that contribute to the uncertain nature of the forward-looking statements include: uncertainties regarding the success, cost and timing of Trevi's product candidate development activities and ongoing and planned clinical trials; the risk that positive data from a clinical trial may not necessarily be predictive of the results of later clinical trials in the same or a different indication; uncertainties regarding Trevi's ability to execute on its strategy; uncertainties with respect to regulatory authorities' views as to the data from Trevi's clinical trials and next steps in the development path for Haduvio in the United States and foreign countries, uncertainties inherent in estimating Trevi's cash runway, future expenses and other financial results, including Trevi's ability to fund future operations, including clinical trials, as well as other risks and uncertainties set forth in the quarterly report on Form 10-Q for the quarter ended September 30, 2024 filed with the Securities and Exchange Commission and in subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Trevi undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Contact Katie Barrett Trevi Therapeutics, Inc. 203-304-2499 [email protected] Media Contact Rosalia Scampoli 914-815-1465 [email protected] SOURCE Trevi Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

近日，河北省牵头开展京津冀药品集采，并对部分通用名独家和竞争不充分化学药品展开集采。 本次集采覆盖的155个药品中涉及多个大品种——雷尼替丁、地佐辛、布托啡诺、氟比洛芬贴等。 这些产品背后更是波及多家上市或知名药企。 根据国家药监局数据，雷尼替丁注射剂涉及华北制药、江苏吴中、亚宝药业、成都倍特等企业。 地佐辛注射剂涉及扬子江药业等。 布托啡诺注射剂涉及恒瑞医药、国药集团、苑东生物、福安药业等。 纳布啡注射剂涉及扬子江药业、人福药业、苑东生物、国药集团等。 21世纪经济报道记者从权威人士处了解到，本次河北药品集采可以不降价报价，但不能中选，最终按省标执行，至于未来是否影响销售、会不会出附加文件，暂未可知。 另外，本次集采还覆盖了超过20个自费药品。 中国医药教育协会医疗装备发展促进工作委员会委员刘检告诉21世纪经济报道，之前有很多自费药被纳入联盟采购，但都不像这一次如此集中。 “但对自费药物进行集采的目的更多在于促进合理用药，因此很难做到带量或对使用量进行兜底。”刘检表示。 波及多家上市药企 本次集采覆盖多个大品种，波及众多上市或知名药企。 对于盐酸雷尼替丁注射液，根据米内网数据，成都倍特该产品在近年来取得高速增长——2020年在中国公立医疗机构终端的销售额仅为2000万元水平，2021年大涨446.8%，销售额突破1亿元。 2022年再涨189.95%，销售额冲破3亿元，2023年增长率为38.12%，销售额首次涨至4.5亿元以上。 雷尼替丁是一种强效的H2-受体阻滞剂，属于抑酸药，可用于消化性溃疡出血、弥漫性胃粘膜病变出血，目前畅销剂型有注射剂、胶囊剂、片剂等。 同在集采目录内的镇痛药布托啡诺属于第二类精神药品，涉及恒瑞医药、福安药业、国药集团等上市公司，其中恒瑞医药的市场份额遥遥领先。 根据PDB数据，从2023年前三季度来看，有3家企业在样本公立医院销售布托啡诺，合计7个剂型规格，均为国产企业。 其中恒瑞医药的三个规格销售金额占比为99.4%，排位第一，福安药业庆余堂制药两个规格占比为0.4%，国药集团国瑞药业两个规格占比为0.2%。 近年来国内公立医院布托啡诺销售金额先升后降。 2019年销售金额大幅上升81.2%，销售数量大幅增长59.1%。 此后三年告别高速增长，2020年至2022年的销售金额分别下降11.6%、上升4.8%和下降8.3%。到2022年，国内公立医院布托啡诺销售额为11.61亿元。 但是到2023年前三季度，布托啡诺的销售金额同比提升33.2%，销售数量同比增长29.6%。 值得关注的是，国内已有地区对布托啡诺进行“砍价”。 2020年，青岛市医保局推动全市公立医疗机构成立药械采购联合体，吸收200多家公立医疗机构，对3类药物进行联合议价采购，最终布托啡诺注射液降幅19.2%。 但仍有新进者希望入局，2024年4月，苑东生物的酒石酸布托啡诺注射液收到国家药监局签发的《药品注册证书》，然而获批不到8个月，就要面对集采。 以及在2024年3月，苑东生物制药的盐酸纳布啡注射液获批上市，同属于第二类精神药品，镇痛效果与吗啡基本相当。 然而与布托啡诺一样，纳布啡注射同样在本次河北集采的名单之内。 2022年，该药物在中国公立医疗机构终端的销售额已超过8亿元。 根据国家药监局数据，目前纳布啡注射液只有国药集团、人福药业、扬子江药业和苑东生物四家企业获批。 用量或难兜底 除了对大品种的覆盖，对24个自费药物进行集采也是河北地区的独特之处。 据了解，2022年7月， “八省二区”第四批集采的18个品种中，有13款药品属于自费药物，集采后价格平均降幅62.7%，最高降幅达94.2%。 但是在刘检看来，本次河北对自费药物密集集采的主要目的可能不是降价，而是为了促进合理用药。 据分析，控费和促进合理用药，是集采的两大作用，对自费药物进行集采，更多是为了解决临床使用合规问题。 此前自费药被纳入集采，多是进入过重点监控或合理用药目录，临床确实有需求但使用不太合规。而不合规的最突出特点，就是费用不经过医保局直接进入医院，现金流系统具有不透明性，那么医院就有了大量使用自费且具有治疗作用药物的动力。 “现在国家要找到多出来的、不合理的临床需求，以及解决自费现金流问题，以此来迫使临床合理合规使用这类药物。集采即是重要方法。”刘检表示。 然而此种目的的集采似乎很难做到带量，因为临床需求尚未识别是否合理，那么当前使用量的合理与否，也仍存疑问。 所以需要通过降价或其他方式识别出合理的使用量，同时也需要用量有一定自主浮动空间。 刘检向21世纪经济报道记者分析，临床用药的合理性问题非常专业，不是几个专家或某个组织就能评判，所以国家只能建立一种反向保护策略——消除不合理使用的因素，把价格降下来，让医院失去创收驱动力，合理的临床需求自然就会有一定呈现。 “就是希望通过集采看到降价后的使用量，进而判断此前是否合理，若降价后临床使用量大幅下降，就说明此药物临床价值有限，主要由创收驱动，下一步就要采取其他方式继续促进合理用药。”刘检说。 但也有产品哪怕被降价或者被挪出医保，使用量依然居高不下——例如地佐辛。 地佐辛已经被部分地区谈判降价、逐渐被各地挪出医保目录，并被纳入第二批国家重点监控合理用药药品目录。 据米内网数据，2020年中国城市公立医院化学药市场的TOP 20品牌金额中，扬子江药业集团的地佐辛注射液位列第一，销售额达54亿元，而2019年这一数据更是接近68亿元。 但哪怕被挪出医保目录、销售额有所下降，其用量仍然不容小觑。 PDB数据库显示，地佐辛在镇痛药中的销售占比有所下降，2019-2022年占比分别为45.1%、45.4%、43.2%和36.8%，2023年前三季度占比进一步下降为27.6%。 但2019年以来，地佐辛的销售额一直稳居镇痛药的首位。 对此，刘检表示，哪怕学术界对地佐辛存有争议，但在急诊科仍然有很大的用药需求量，所以是否进医保和合理用药之间其实不存在强关联。 “集采也一样，如果降价后临床使用量在增加，就说明此产品确实有临床刚需，降价也就能够降低患者负担，这是国家医改中的‘一石二鸟’甚至‘一石三鸟’之策。因此，当以检验是否合理用药以及促进合理用药为目的时，就很难给药品进行用量的兜底。”刘检说道。 来源：21世纪经济报道 商务合作 130 6172 3098 zakk.cui@siqibest.com 点击 阅读原文 了解更多