Desflurane

Each puff of a metered-dose inhaler expels a potent hydrofluorocarbon gas with upwards of 3,000 times the greenhouse warming potential of carbon dioxide. It is becoming more widely known that the healthcare sector is a significant contributor to greenhouse gas emissions, accounting for nearly 9% of the total in the U.S. But perhaps less recognized is that common substances routinely used in care—anesthetic gasses, even inhalers—are part of the problem.  Digging into the science, the irony becomes obvious: The mechanisms for keeping patients safe during a procedure or an asthma attack are also poisoning the environment. Desflurane, a common inhaled anesthetic, has heat-trapping properties hundreds to thousands of times greater than carbon dioxide. Meanwhile, nitrous oxide, a sedative used in surgery, has a warming potential 273 times that of carbon dioxide and greatly damages the ozone layer, which is crucial to absorbing harmful radiation from the sun. Even metered-dose inhalers that contain a seemingly small amount of hydrofluorocarbon gas have been shown to contribute meaningfully to emissions. At the end of last month, a small group of safety net hospitals and municipal health departments joined a 10-month collaborative in an effort to test decarbonization interventions and measure their results. The cohort, led by the Institute for Healthcare Improvement, includes sustainability professionals, clinicians and other healthcare leaders across six states. Each organization is expected to pick an improvement project and will receive support from experts and peers to carry it out. “For safety net hospitals who deliver care on tight margins and serve patient populations disproportionately impacted by the effects of climate change, investing in lowering carbon emissions holds the potential to advance their mission, strategy, and financial health,” the IHI said in its request for applications. The last IHI decarbonization cohort wrapped up in December 2023. More than a dozen organizations participated in 16 quality improvement projects. More than half measured reductions either in waste or purchases of anesthetic gas. Several sites decommissioned central nitrous oxide and eliminated desflurane from their operating rooms. Fierce Healthcare spoke to some of the participants about what they were able to achieve.   Thinking big by going small   Nitrous oxide, commonly used in dentistry, can be stored in one of two ways: in large centralized tanks that deliver the gas to operating rooms through piping, or in portable cylinder tanks. Choosing between the two might seem inconsequential. Indeed, one benefit of a centralized system is having to change the tanks less often. However, several hospitals around the world recently discovered that between 75% and 95% of their nitrous oxide leaks out through the central piping before it ever reaches the patient, wasting resources and polluting the atmosphere.  Addressing this waste was a goal for Northwell, which joined the last IHI decarbonization cohort. But to do so, the health system would need to figure out how the gas was being procured and used at its facilities. With more than 800 ambulatory sites and 20-odd hospitals, this would prove no small task.  “When you’re as big as we are, that was quite a challenge,” Teresa Murray Amato, M.D., VP of Clinical Sustainability and Resource Stewardship and director of geriatric emergency medicine at Northwell Health, told Fierce Healthcare. Amato started by looking for allies—“probably the best way to start,” she said—such as the head of anesthesia at her own hospital, who was really interested in sustainability. “Try to go for the easiest first,” Amato said.  As part of its emergency management work, Northwell works to ensure it has a three-day supply of essential resources. Keeping that in mind, Amato’s team decided to test if anesthesiologists would have enough nitrous oxide if they were to only use the portable tanks for three days. The clinicians recorded how long they used the gas and at what flow rates.  That information and anecdotal conversations revealed the gas was being used very infrequently, and Amato’s team extrapolated the use and determined that decommissioning centralized nitrous oxide systems would not negatively impact clinical practice. Spreading awareness of the environmental harms also reduced nonessential uses of nitrous oxide. For Northwell, eliminating the large tanks didn't mean getting rid of nitrous oxide altogether, it just consolidates resources in a more practical way. There are some cost savings too, though not as great as the enormous benefits to the environment. Even if someone left a portable tank open by accident and it leaked entirely, the impact would be a fraction of that of a centralized tank, according to Amato. “It’s such a simple solution, but it’s a challenge in a very large, highly matrixed organization,” Amato said. Armed with the success from this project, the proof of concept is now helping fuel other similar projects forward. “Now, everybody wants to be the next one to go,” Amato noted. Northwell’s new goal is to have almost no central tanks by the end of 2024.   The dark side of inhalers    To expel the medication, each puff of a metered-dose inhaler relies on a hydrofluorocarbon gas, a potent greenhouse gas with upwards of 3,000 times the warming potential of carbon dioxide. This gas contributes to climate change, which can lead to events that worsen asthma and in turn further drive up the use of inhalers. Though each inhaler seems small, 144 million were prescribed in the U.S. alone in 2020. And three-quarters of those contained the gas. In England, metered-dose inhalers have been found to represent 3% of total National Health Service carbon emissions, equal to the carbon emissions from all the electricity used by the NHS. “They actually have a pretty substantial contribution to healthcare’s overall environmental impact,” Gregg Furie, M.D., medical director for climate and sustainability at Brigham and Women's Hospital, told Fierce Healthcare.  Alternatives, like dry powder and soft mist inhalers, exist. This was an area Mass General Brigham wanted to tackle through the IHI collaborative. “We saw it as an opportunity to provide some structure to a project that we initially wanted to focus on,” Furie said.  The health system leaned on the institute's staff to learn how to bring a range of diverse stakeholders to the table. “There are way more stakeholders than you think there are,” Jonathan Slutzman, medical director for environmental sustainability at Mass General Hospital, told Fierce Healthcare. The collaboration also offered regular check-ins and a framework for accountability, which forced momentum internally, Slutzman added. Their goal was to reduce the overall share of metered-dose inhalers that are prescribed and to shift to alternatives where possible. They also hoped to raise awareness of the environmental impact of certain inhalers within the organization. They don't yet have concrete data on the project's outcomes to share. “This is not something that many practitioners are aware of,” Furie noted. “We are the ones who ultimately prescribe these devices… this is something that we feel we have real agency to do something about.” While the shift to alternative inhalers across the U.S. has been slow, Furie expects that to begin to change. That shift is being partly driven by increased scrutiny of the patent process and high prescription costs at the federal level. Apart from provider-driven efforts to move away from metered-dose inhalers, other solutions need to come from industry innovations and policy reform, per Furie. The FDA is studying the challenges of developing inhalers with a lower warming potential—but Slutzman believes the agency can be doing more to protect sustainability. One could argue that environmental impact should be a part of evaluating the safety of a drug, he said. “FDA should be able to encourage or make it easier for drug delivery devices that we know are environmentally better,” Slutzman said. “That would enable us to prescribe better inhalers.”   Centering climate as a broader priority    The idea for the collaboration began when the Agency for Healthcare Research and Quality commissioned IHI to develop a primer on decarbonization. IHI sought input from an expert panel, collaborating with the National Academy of Medicine and Health Care Without Harm to co-design resources along the way. “There are more and more organizations engaging in this area, which is very exciting and it is very important to ensure there is no duplication of efforts,” IHI Director Bhargavi Sampath, MPH, told Fierce Healthcare. Afterwards, the organization wanted to put the primer into practice by way of a collaborative, intended to inspire leader engagement, boost teams’ confidence and skills and build will across departments. “It really takes a very big group of people to do this work,” said IHI Project Director Becka DeSmidt.  Anyone looking for organizational buy-in on sustainability initiatives is advised to stress the potential for cost savings, the moral obligation to address the climate for patient health and that prioritizing such initiatives can help retain current or recruit future staff. “We’ve heard a lot from clinicians directly about how meaningful and engaging this work can be and clinician advocacy can be really powerful in helping an organization make these commitments,” DeSmidt told Fierce Healthcare. Two organizations participating in the collaborative successfully made the case for additional sustainability hires by leveraging the progress they were making on their projects as well as the cost savings they were seeing. Two others integrated clinical decarbonization metrics into their key performance indicators amid “the growing acceptance of integrating climate priorities into broader system strategies,” DeSmidt said. “Something we were really excited about was the promise of bringing climate more centrally into health system priorities,” Sampath echoed, “to advance some of the climate work that really needs to take place more locally at the frontline and with clinician leadership.”

精彩内容 近日，恒瑞医药创新药研发进展不断：SHR-A1811(Her2 ADC)纳入突破性疗法，氟唑帕利新适应症获批，SHR-4849、SHR-9539、HRS-5346等首次在国内获批临床......目前公司有23款创新药在国内获批，2023年创新药收入首破百亿；178款新药（150款1类新药）处于申请临床及以上阶段，其中27款已报产或步入III期临床，上市可期；2019年至今拿下19个首仿，10个新品在路上。近年来公司海外BD动作不断，17个创新药的临床试验顺利推进中。 创新药收入首破百亿！150款1类新药霸屏 受集采和医保降价影响，2021、2022年恒瑞医药陷入营收、净利双降的窘境。但在集采影响逐渐出清及创新药加持下，2023年公司业绩实现止跌回升，并将上升势头延续到了2024年一季度。 4月17日晚间，恒瑞医药发布2023年年报及2024年一季度报。2023年公司实现营业收入228.20亿元，同比增长7.26%；归母净利润43.02亿元，同比增长10.14%。2024年一季度，公司实现营收59.98亿元，同比增长9.2%；归母净利润13.69亿元，同比增长10.48%。 在经历集采的阵痛后，创新药已然成为恒瑞医药的重心，并逐渐成为其业绩增长的主要推动力。2023年公司创新药收入达106.37亿元（含税，不含对外许可收入），虽然面临外部环境变化、产品降价及准入难等因素影响，仍然实现了22.1%的同比增长，占营收比重达到46.6%。 截至目前，恒瑞医药已在国内获批上市14款自研创新药（13款1类新药）、2款合作引进创新药、6款2类改良型新药及1款生物类似药，涉及抗肿瘤、麻醉镇痛、消化代谢、抗感染等多个治疗领域，创新成果稳居行业领先地位。 得益于国家医保助力及出色的商业化能力，恒瑞医药近年来获批上市的新药放量明显，如2021年6月获批的海曲泊帕乙醇胺，2023年在中国三大终端六大市场（统计范围详见本文末）终端的销售额超过12亿元，同比增长约104%；同样于2021年6月获批的贝伐珠单抗注射液是恒瑞医药首款生物类似药，2023年销售额突破6亿元，同比增长约102%；2021年底获批的达尔西利，2023年销售额超过2亿元，同比增长约506%；2022年6月获批的瑞维鲁胺，2023年销售额超过2亿元。 为保证创新成果产出，恒瑞医药持续加大创新力度。2023年公司研发投入61.50亿元，近十年来（2014-2023）累计研发投入接近350亿元。米内网数据显示，含合作引进的新药在内，目前恒瑞医药在国内有178款新药（不含已有批文、撤回或不批准品种）处于申请临床及以上阶段，其中有150款为1类新药。 恒瑞医药国内在研新药来源：米内网综合数据库 从研发进度看，27款新药（20款1类新药）处于NDA或III期临床阶段（不含II/III期临床），上市可期；从治疗类别看，处于获批临床及以上阶段的173款新药涵盖13个治疗大类，集中在抗肿瘤和免疫调节剂、消化系统及代谢药、神经系统药物三大领域。 ADC为恒瑞医药在抗肿瘤领域最为重要的布局，目前公司已有11个新型、具有差异化的ADC分子成功获批临床，其中注射用SHR-A1811（Her2 ADC）、注射用SHR-A1921（Trop2 ADC）已步入III期临床，注射用SHR-A1904（Claudin18.2 ADC）处于Ib/III期临床，注射用SHR-A2009（HER3 ADC）、注射用SHR-A1912（CD79b ADC）、注射用SHR-A2102（Nectin-4 ADC）等处于I/II期临床。 针对热门的CLP-1靶点，恒瑞医药已有6款相关产品获批临床，其中长效胰岛素+GLP-1类似物HR17031注射液（2型糖尿病）、GIP/GLP-1双重激动剂HRS9531注射液（减重）已步入III期临床；GLP-1受体激动剂诺利糖肽注射液（2型糖尿病/肥胖）、口服GLP-1受体激动剂HRS-7535片（2型糖尿病/肥胖）正在开展II期临床；GLP-1/GCGR双重激动剂SHR-1816注射液（糖尿病）、口服GLP-1/GIP双受体激动剂HRS9531片（超重或肥胖/2型糖尿病）处于I期临床。 拿下19个首仿！10个新品在路上 除了不断加码创新药，恒瑞医药在仿制药亦有布局，重点关注首仿、高端剂型等。 据不完全统计，2019年以来，公司有19个首仿（含剂型首仿）在国内获批生产并视同过评，其中注射用塞替派、环磷酰胺胶囊、布比卡因脂质体注射液、昂丹司琼口腔溶解薄膜、盐酸艾司氯胺酮注射液至今仍为独家品种，10%脂肪乳(OO)/5.5%氨基酸(15)/葡萄糖(20%)注射液至今仍为国产独家品种。 2019年以来恒瑞医药获批上市的首仿来源：米内网中国申报进度（MED）数据库 截至目前，恒瑞医药有65个品种过评/视同过评，其中36个为国内首家，注射用塞替派、布比卡因脂质体注射液、10%脂肪乳(OO)/5.5%氨基酸(15)/葡萄糖(20%)注射液、美司钠注射液、环磷酰胺胶囊、碘化油注射液(罂粟乙碘油注射液)、昂丹司琼口腔溶解薄膜、注射用环磷酰胺、盐酸艾司氯胺酮注射液、吸入用地氟烷等为独家过评。 恒瑞医药已过评品种中，共有30余个品种被纳入国采，其中有24个品种中标。公司多个核心仿制药已被纳入集采，集采影响将逐步出清。米内网数据显示，2023年中国公立医疗机构终端恒瑞医药销售额超10亿元的仿制药中，1个已被纳入集采，2个未被纳入集采且暂不满足初步条件，1个未被纳入集采且满足初步入围条件。 除去已获批/撤回或不批准品种，目前恒瑞医药还有10个新分类申报品种在审，其中9个品种暂无首仿（含剂型首仿）获批，剩下1个品种仅有1家国产企业及原研厂家拥有生产批文。 恒瑞医药新分类申报且在审品种来源：米内网中国申报进度（MED）数据库 镓[68Ga]伊索曲肽注射液、镥[177Lu]氧奥曲肽注射液是恒瑞医药在核药领域布局的首对放射性精准诊疗产品；艾氟洛芬贴剂是公司首款以新注册分类申报的贴膏剂产品；ω-3鱼油中长链脂肪乳/氨基酸(16)/葡萄糖(30%)注射液为肠外营养三腔袋，复方氨基酸(16AA)/葡萄糖(12.6%)电解质注射液为肠外营养双室袋。 探索出海新模式，国际化进程持续推进 5月16日晚，恒瑞医药公告称，将具有自主知识产权的GLP-1组合创新药HRS-7535、HRS9531、HRS-4729在除大中华区以外的全球范围内开发、生产和商业化的独家权利有偿许可给美国Hercules公司。 根据协议，恒瑞医药将获得1.1亿美元的首付款和近期里程碑款，累计不超过2亿美元的临床开发及监管里程碑款，累计不超过57.25亿美元的销售里程碑款。作为对外许可交易对价的一部分，恒瑞医药还将取得美国Hercules公司19.9%的股权，成为Hercules的股东之一。据悉，这种交易模式在海外MNC中不乏先例，但在国内确实是比较新的探索。 作为国内创新药出海的活跃分子，恒瑞医药近两年来BD动作不断：2023年，从SHR2554（EZH2抑制剂）开启首章，到与Merck达成最高可达14亿欧元的交易，一年时间共达成5起海外BD授权，交易总额超40亿美元。值得一提的是，与Merck的合作是恒瑞医药首次与全球大型跨国企业牵手；2024年，开篇即王炸，不仅达成超60亿美元的合作（超过2023年全年交易总额），还入股了Hercules，探索出海新模式。 2023年以来恒瑞医药部分license-out项目来源：公司公告，米内网整理 国际化是恒瑞医药多年来坚持的战略方针，公司坚持自主研发与开放合作并重，在内生发展的基础上加强国际合作，已从最初的仿制药出口逐步走向“仿制药+创新药”出口的并行阶段。 通过与多家药企合作，恒瑞医药将卡瑞利珠单抗、吡咯替尼、SHR2554、SHR-1701、SHR-1905、SHR0302、SHR-A1904、HRS-1167、HRS-7535、HRS9531、HRS-4729等多款具有自主知识产权的创新药对外授权。 在自主研发上，近几年来，恒瑞医药有多个仿制药的ANDA申请获得美国FDA批准，包括他克莫司缓释胶囊、钆布醇注射液、碘克沙醇注射液、钆特酸葡胺注射液等，其中他克莫司缓释胶囊为中美双首仿。 此外，截至2024年3月31日，恒瑞医药已在海外布局了17个创新药，其中PD-1单抗卡瑞利珠单抗（联合阿帕替尼一线治疗晚期肝细胞癌）已向FDA递交新药上市申请（BLA），SHR0302、吡咯替尼、氟唑帕利、海曲泊帕乙醇胺等均处于III期临床阶段。 恒瑞医药海外创新药临床进展（截至2024年3月31日） 资料来源：米内网数据库、公司公告等注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至6月7日，如有疏漏，欢迎指正！ 本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦