Lenacapavir Sodium

编者按：本文来自药智网，作者白纸扇；赛柏蓝授权转载，编辑凯西012025Q1畅销药TOP10GLP-1药物市场规模继续扩大，司美格鲁肽一季度销售额近80亿美元，替尔泊肽销售额61.5亿美元，成为增长最快的领域。肿瘤领域，Keytruda虽然保持了4%的同比增长，但环比已开始下滑。自免领域，继HUMIRA（修美乐）后，STELARA也因为专利到期，销售额开始大幅下滑，已跌出TOP10榜单。而新任自免药物DUPIXENT也增长疲软，亟待破局。数据来源：根据公开资料整理023款GLP-1药物上榜作为划时代的肿瘤治疗药物——Keytruda（K药，帕博利珠单抗），自2014年9月首次获美国FDA批准上市以来，其临床适应症不断拓展，获批适应症达到40项，在研适应症百余项。2023年其全球销售收入250.11亿美元，问鼎全球“药王”，并在2024年销售额继续增长18%，达到295亿美元。然而“药王”在多年高增长后，正面临市场竞争的空前压力，销量已呈现触顶之势。据默沙东财报，K药2025Q1销售额72.1亿美元，同比增长4%，而环比首度出现下滑。图片来源：空之客排名第二的是诺和诺德的降糖药Ozempic（司美格鲁肽），2025年Q1销售额327.21亿丹麦克朗，约46亿美元（按今年第一季度平均汇率计算：1丹麦克朗=0.141美元），同比增长18%。值得注意的是，排名第10的Wegovy为司美格鲁肽的另一品牌，用于体重控制。该药2025Q1销售额173.6亿丹麦克朗，约24亿美元，同比增长85%。此外，司美格鲁肽的口服降糖制剂Rybelsus销售额为56.95亿丹麦克朗（约8.03亿美元）。如果合并计算司美格鲁肽的三个品牌，合计销售额约79亿美元，超过K药，成为新的“药王”。紧随Ozempic的是礼来的Mounjaro（替尔泊肽）。作为GLP-1/GIP受体双重激动剂，其创新机制使其在糖尿病治疗中展现出优越的血糖控制效果，还具备显著的减重效果。虽然2022年才上市，晚于司美格鲁肽5年，但其单季销售额已达38.4亿美元。另外，替尔泊肽减肥品牌Zepbound在今年第一季度销售额23.1亿美元，两品牌合计销售额61.5亿美元，是司美格鲁肽的最大竞争对手，也是未来药王的有力竞争者。不过，与去年相比，今年的GLP-1药物市场竞争或许将更加激烈，尤其是美国市场已进入白热化阶段。诺和诺德演示PPT显示，司美格鲁肽的市场份额正在被替尔泊肽蚕食。无论是在糖尿病还是减重市场，替尔泊肽的总处方量和新处方量都在逆袭，超过司美格鲁肽。图片来源：诺和诺德财报而替尔泊肽虽然同比增长率超过100%，但环比增速仅剩13%，或许GLP-1市场将提前进入存量竞争阶段。为应对竞争，礼来推出Zepbound小剂量装，以价格优势争夺市场。诺和诺德则一边争取美国PBM公司的支持。近期，美国PBM公司CVS Health宣布，将于今年7月1日起，将礼来的Zepbound从其“首选目录”中删除，相反，CVS将优先考虑诺和诺德的Wegovy。这一举措被海外分析机构视为GLP-1价格战升级的标志性信号。一边拓展中国等新市场。2024年6月，司美格鲁肽减重适应症在中国获批上市，商品名为诺和盈，11月中旬在国内上市，2025Q1已斩获6.86亿丹麦克朗。03半数产品增长乏力GLP-1之外，其他领域就没那么强劲的增长势头了。肿瘤领域，K药销量已有触顶之势，而且未来将面临专利到期和双抗等新型疗法迭代等多重挑战。不过，强生的多发性骨髓瘤明星产品Darzalex（达雷妥尤单抗）上市十年仍保持着20%的同比增速，未来还有不少增长空间。自免领域，在修美乐专利到期后，赛诺菲和再生元的IL-4R抗体Dupixent（度普利尤单抗）登顶“药王”。2025Q1其全球销售额达到34.8亿欧元，同比增长20.3%。但相较于上一季度环比增长仅为0.69%，已显增长疲态。虽然去年斩获了慢性阻塞性肺病(COPD)这一备受瞩目的适应症，但对销量的影响十分有限。今年4月，Dupixent又斩获慢性自发性荨麻疹适应症，希望能助力其单季销售额突破35亿欧元。比起Dupixent的增长乏力，艾伯维的抗IL-23单抗Skyrizi（利生奇珠单抗）强势崛起。其Q1销售额达到34.3亿美元，同比增长高达71%。而艾伯维的另一款自免新星Rinvoq（乌帕替尼）在Q1销售额17.2亿美元，同比增长57%，也有望挤进TOP10行列。凭此，艾伯维有望在今年夺回其自免领域领导地位。TOP10榜单中还有3款小分子药物，但未来前景都不太乐观。BMS的Eliquis（阿哌沙班）是一款口服抗凝药物，具有使用方便、疗效确切等特点，在临床上广泛应用于血栓性疾病的预防和治疗，长期以来一直保持着较高的市场份额。但是今年销售额已开始下滑，其Q1收入35.7亿美元（-4%），而且其核心专利将于2026年到期，未来销量可能进一步下滑。吉利德的抗艾滋病药Biktarvy（比克替拉韦+恩曲他滨+丙酚替诺福韦）凭借有效的抗病毒作用和良好的耐受性，成为多数艾滋病患者的首选治疗药物之一。2025年Q1其销售额为31.50亿美元，同比增长7%，但环比下降17%，与此前相比呈现出放缓态势。不过，吉利德早已准备好迭代产品，在2033年Biktarvy失去市场独占权之前，有望推出九款HIV产品，包括每年两次注射的新型HIV长效疗法Lenacapavir（来那帕韦），该药于2022年在欧美获批用于治疗HIV-1感染，并被《科学》杂志评选为2024年度重大突破药物之一。此外，lenacapavir预计将于2025年夏季获批用于HIV-1感染的暴露前预防（PrEP）。福泰制药的囊性纤维化药物TRIKAFTA/KAFTRIO在2024年销售额成功突破百亿美元，但今年一季度数据显示，其销量已接近天花板。Q1销售额25.4亿美元，同比增长2%，环比下降7%。04有望挺进前10的品种在2025年第一季度的畅销药TOP10榜单中，糖尿病与肥胖领域已超越肿瘤、自身免疫疾病领域，成为孕育畅销药最多的新阵地，映射出全球医药市场周期的不断演变。目前，Ozempic、Mounjaro和Wegovy这三款产品强势跻身全球畅销药TOP10榜单前列，而Zepbound高速增长，不久后也将杀入前十行列。肿瘤领域自2014年PD-1单抗问世以来，免疫疗法迎来了十年的高速发展，但K药登顶“药王”后，增长已显著放缓。不过，新一代抗肿瘤药物ADC、双抗已展现出迭代优势。ADC领域，第一三共和阿斯利康的Enhertu（德曲妥珠单抗）快速放量，单季度销售额已突破10亿美元，今年全年预计将达到50亿美元。双抗领域，康方生物的依沃西单抗打败K药，成为备受期待的下一代肿瘤免疫治疗方案。自免领域，Humira和Stelara两大百亿美元大单品专利到期后，销售额大幅下滑，已无缘前十。但艾伯维的两款自免新星正强势崛起，Skyrizi已成为仅次于Dupixent的自免畅销药，而Rinvoq目前排名前30，未来也有望挺进前十。另外，自免领域还在孕育新的大单品，Argenx公司的FcRn拮抗剂艾加莫德（Vyvgart）于2021年12月首次获得FDA批准上市，2023年便已跨入十亿美元俱乐部。目前该药已批三个适应症，全身性重症肌无力（gMG）、原发性免疫性血小板减少症（ITP）和慢性炎性脱髓鞘性多发性神经病（CIDP）。该药今年一季度收入7.9亿美元，同比增长99%。目前，Argenx还在挖掘Vyvgart的治疗潜力，十余个新适应症正在探索中，未来其销售峰值可能超过百亿美元。图片来源：药智数据未来，随着医药研发的不断深入和市场需求的变化，畅销药榜单的格局还将会继续发生新的变化，让我们拭目以待。参考资料：1.各企业2025年第一季度报2.空之客：【医苑观畴】2025年一季度海外药企进展更新：默沙东MRK3.E药经理人：美国最大PBM“站队”诺和诺德，礼来大跌10%，GLP-1“双姝”价格战开打！4.抗体圈：JPM 2025|吉利德Biktarvy在2033年失去市场独占权前，有望推出九款HIV产品END内容沟通：郑瑶（13810174402）

iStock, Jorm Sangsorn As the Trump administration slashes funding for HIV-related research and infrastructure, Gilead, Immunocore and more are targeting the next goalpost: a cure. Since Donald Trump took office in January, the National Institutes of Health has seen its funding cut for numerous HIV studies, alarming researchers and likely reducing the chances of achieving the president’s own 2019 goal of ending HIV in the U.S. by 2030. Against this backdrop, biopharma companies such as Gilead Sciences and Immunocore are pursuing the holy grail—a cure. Medicine has made considerable strides against HIV since the advent of the epidemic in 1981. The death rate from HIV in the U.S. fell from 16.2 per 100,000 infected people in 1995 to 1.3 per 100,000 in 2022, according to Statista , as antiretroviral therapy (ART) controlled the virus in people with HIV and, more recently, pre-exposure prophylaxis (PrEP) allowed high-risk individuals to protect themselves against infection in the first place. This progress could be in danger, however. As of April 11, the NIH had cancelled approximately 770 active research grants, Scientific American reported . Of the projects axed as of that date, 29% were related to HIV/AIDS, according to the publication. These programs and those focused on COVID-19 made up a disproportionate amount of the culled research, accounting for 46% of halted projects despite these areas garnering less than 4% of 2024 NIH grants. Martin Rhee, director of clinical research at Gilead, said that NIH funding is key to HIV research. “Federal funding is really, really important, for scientific innovation, but also at the level of implementation as well,” he told BioSpace . Rhee pointed to the AIDS Clinical Trials Group (ACTG) and the HIV Prevention Trials Network (HPTN) as two federally funded groups that have “really played an important role” in bringing drugs to the market. Gilead, whose ART Sunlenca (lenacapavir) earned FDA approval in December 2022, has partnerships with ACTG for clinical trials. As this arm of the HIV space is challenged by cuts under the new administration, Gilead and other private sector players are carrying on the mission. Industry “also [has] a very, very important role to play in drug development,” Rhee said, “and we will continue to focus on scientific innovation and really bringing important scientific discoveries to patients who need them.” Now that the virus is largely under control in the U.S., the focus is on keeping it that way with PrEP and discovering a cure for the now decades-old threat. Going for a Cure Near-term, the goal in the HIV space is to offer options that require less frequent dosing. “When you look at the underlying reasons why [disease in] some people may not be suppressed, often what comes up is the stigma of daily pill-taking and also just the sheer burden of having to take a pill every day,” Rhee explained. Currently approved for as a twice-yearly injection, Gilead is looking to reduce that frequency to once per year. At the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in March, Gilead presented Phase I data showing that two novel once-yearly formulations of lenacapavir led to higher plasma concentrations of the drug than were needed to show efficacy in Phase III trials of patients treated twice a year. The company expects to launch a Phase III trial for once-yearly lenacapavir in the second half of 2025, according to a March press release . Alongside Gilead, GSK and ViiV are also working on long-acting antivirals. But the ultimate goal is to totally rid patients of the virus such that treatment is not necessary at all. “Cure will always be, I think, the final goal post in some ways,” Rhee said. The challenge, he continued, is that HIV has never been cured naturally. “We have elite controllers, but really no good example of a naturally cured infection.” There have been cases, however, that have spurred hope for a curative HIV treatment. The most famous is probably that of Timothy Ray Brown, aka “the Berlin patient.” Brown, who was diagnosed with HIV in 1995, developed acute myeloid leukemia 12 years later. Brown received a bone marrow transplant from a donor who was naturally resistant to HIV thanks to a rare mutation in the CCR5 gene. Miraculously, the virus was undetectable in his system just three months later despite the fact that Brown had stopped taking his antiviral medicine the day of the procedure. From then until his death from cancer in September 2020, the HIV was never detected again. Unfortunately, bone marrow transplants aren’t feasible for every patient. “That’s been the major, major challenge within the HIV cure field, because we want to develop an intervention and regimen that is scalable,” Rhee said. But the virus doesn’t make it easy. “Biologically and scientifically, it is very, very challenging because of the diversity of the virus [and] also the way it evades the immune system and goes undetected . . . through a reservoir,” he explained. Historically, no one has been able to show any impact on the reservoir, David Berman, EVP of research and development at Immunocore, told BioSpace . But that doesn’t mean biopharma is giving up. While antiretroviral therapies block the HIV from replicating, they do not eliminate the reservoir. Although fully eradicating the virus from the body—what might be called a true cure—is still a lofty goal, researchers are focused on a functional cure, or remission, where the reservoir has shrunk to a smaller size and immune control is induced for what remains. Devi SanGupta, head of Gilead’s HIV cure strategy, said that, most likely, “a combination of agents will be required both really for a functional cure, or a complete cure.” Among those agents could be Gilead’s bispecific T cell engager GS-8588. One arm of the molecule targets HIV that is expressed on infected cells, while the other targets T cells, explained SanGupta. “It’s actually trying to bring the T cells together with the infected HIV infected cells, so that those T cells can then destroy the infected cells.” Pennsylvania and Maryland–based Immunocore is also developing a bispecific T cell engager. In January 2022, Kimmtrak was approved by the FDA for uveal melanoma, becoming the first T cell receptor therapy to win the regulator’s greenlight. “Now we’re turning to HIV,” Berman said. “I think the dream has always been to have some type of immunotherapy approach where you can harness the immune system to target the virus.” At CROI, Immunocore presented data from a Phase I/II trial showing that its candidate, IMC-M113V, elicited “signals of dose-dependent viral control after antiretroviral treatment (ART) is interrupted,” according to a March press release . Typically, one in a million T cells in the blood will have the virus in them, so a key data point for Immunocore was looking at the level of HIV RNA in the T cells. And reductions were seen, “so we believe the mechanism may be working,” Berman said. In the trial, 16 patients with HIV taking ART were given weekly IV infusions of IMC-M113V for 12 weeks. After stopping all treatment, three participants given the highest dose of 300 micrograms saw an initial rebound in viral load, “and then it went back down,” Berman said. Immunocore will continue to monitor these patients to see if the virus will “start to burn itself out.” The company also plans to test higher dose levels. Meanwhile, Excision is taking a CRISPR-based approach, claiming on its website to have “demonstrated the first functional therapeutic treatment for HIV in animals.” In May 2024, the biotech presented data from a Phase I/II study of EBT-101, showing “important clinical evidence that a gene editing treatment modality can be safely delivered for targeting the HIV DNA reservoirs in human cells,” Rachel Presti, professor of Medicine at Washington University School of Medicine in St. Louis and a principal investigator on the trial, said in a statement . Achieving a functional cure for HIV is important for three reasons, Berman stressed. First, even with the virus suppressed, the reservoir can cause mild but chronic inflammation, which can have an impact on the cardiovascular system, he said. “So there’s a need to get that chronic inflammation under control.” Second, with ART, there is a risk of resistance, particularly when people are inconsistent with treatment. And finally, there’s a social stigma when somebody has transmissible levels of HIV. Ecosystem Disrupted Unfortunately, it may be this very social stigma that weakens one of HIV research’s prime funding sources. “I can only predict that [the NIH cuts are] because of the population that it affects,” John Meade, senior program manager for Policy at the AIDS Vaccine Advocacy Coalition (AVAC), told BioSpace . “HIV research has always been based on the marginalized and the most vulnerable populations, and cutting those will only hurt those populations, which I think is the goal of this administration.” Whatever the reason, the HIV space is feeling the pressure, and SanGupta emphasized the role that Gilead and its peers play in ensuring the research continues. “It’s an ecosystem,” she said, “and we’re doing our best in that ecosystem to keep things moving and also making sure that we’re engaging with the lawmakers as appropriate.”