Tirzepatide

近期，美国卫生与公众服务部（HHS）在肥胖症药物医保覆盖政策上的一系列动作，引发了社会各界的广泛关注。这不仅关乎众多肥胖症患者的切身利益，也对医药行业的发展有着深远影响。与此同时，HHS 内部的大规模调整仍在持续，使得这一事件背后的走向更加扑朔迷离。医保政策反转，未来存变数特朗普政府上周推翻了拜登时期提出的将抗肥胖治疗纳入医疗保险（Medicare）D 部分覆盖范围的提案。这一决定让众多期待能通过医保获取诺和诺德的 Wegovy、礼来的 Zepbound 等抗肥胖药物的患者大失所望。这些药物每月治疗费用约 1100 美元，根据 2024 年 10 月美国国会预算办公室报告，若纳入医保，2026 - 2034 年联邦支出可能因此增加约 350 亿美元 ，高昂的成本或许是政策反转的重要原因。不过，HHS 并未完全堵死未来的可能性。本周一，HHS 发言人在回应 Endpoints News 时表示，虽然当前该提案 “不合适”，但部门 “可能会考虑未来的政策选项”，前提是综合评估这些药物的成本效益平衡。发言人提到，医疗保险和医疗补助服务中心（CMS）在进一步审查药物潜在益处（如更新的临床适应症）和相关成本（包括对州医疗补助机构等利益相关者的财政影响）后，可能会重新审视抗肥胖药物的医保政策。这一表态给未来医保覆盖肥胖症药物带来了一丝希望。值得注意的是，礼来和诺和诺德等公司一直在拓展药物适应症。今年 1 月，诺和诺德的 Ozempic 获得 FDA 批准用于治疗慢性肾脏病；去年 12 月，礼来的 Zepbound 获批用于治疗睡眠呼吸暂停。此外，这些公司还在探索肥胖症药物在多囊卵巢综合征（MASH）、阿尔茨海默病、帕金森病和癌症等疾病方面的应用。Jefferies 分析师罗杰・宋认为，Medicare 医保政策的走向可能成为扩大肥胖症药物覆盖范围的关键信号。HHS 内部变动，引发连锁反应在医保政策变动的同时，HHS 内部也经历着大规模变革。自 2 月肯尼迪担任卫生部长以来，以提高效率为名，HHS 进行了大规模裁员，FDA 也未能幸免。据统计，自年初以来，HHS 已有约 2 万名员工离职或被裁，占原员工总数的 25% 左右。上周，美国参议员比尔・卡西迪（共和党，路易斯安那州）和伯尼・桑德斯（独立党，佛蒙特州）致信肯尼迪，要求他在 4 月 10 日美国参议院卫生、教育、劳工和养老金委员会（HELP）听证会上就大规模人事变动做出解释。然而，截至目前，该听证会并未如期举行。HELP 委员会办事员办公室的一名工作人员助理向 Endpoints News 表示，本周 “肯定不会举行” 听证会。该委员会 4 月 14 日 - 25 日将进入休会期，之后是否会安排听证会听取肯尼迪的证词仍有待观察。除了裁员，肯尼迪在 3 月还宣布成立新机构 “健康美国管理局”，将药物滥用和心理健康服务管理局、国家职业安全与健康研究所等现有部门纳入其中。这一系列变动显示出 HHS 正在进行全面的架构调整，其最终目标和实际影响仍有待进一步观察。HHS 在肥胖症药物医保政策上的摇摆不定，以及内部的持续变革，给肥胖症药物市场和医疗保障体系带来了诸多不确定性。未来，HHS 能否在平衡财政支出和满足患者需求之间找到合适的解决方案，医保政策又将如何影响肥胖症药物的研发和推广，值得持续关注。参考来源：https://www.biospace.com/policy/hhs-leaves-door-open-to-future-medicare-coverage-of-obesity-drugs识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

iStock, leolintang Wegovy and Zepbound are just the latest drug dyads to face-off in the competitive pharma market, continuing a legacy of rivalry that includes blockbuster drugs Keytruda, Humira and Eliquis. Obesity is the most competitive space in biopharma right now. The two frontrunners, Novo Nordisk and Eli Lilly, are locked in a very tight fight for leadership in a market that by some estimates could reach a jaw-dropping $150 billion in the next few years. Novo moved first. Its GLP-1 analog semaglutide was first cleared by the FDA in 2017 as Ozempic for type 2 diabetes. Some four years later, in July 2021, semaglutide won another approval as Wegovy , this time specifically indicated for chronic weight management. Lilly’s weight-loss blockbuster tirzepatide, in comparison, is a relative late-comer, first reaching the U.S. market in 2022 as Mounjaro for type 2 diabetes Then in November 2023, the FDA approved the drug as Zepbound for obesity , setting up the head-to-head battle with Wegovy in the massive and swiftly growing weight loss market. Despite being years behind, Lilly is chipping away at Novo’s lead. Costanza Alciati, pharma analyst at GlobalData, told BioSpace in an email that tirzepatide’s efficacy edge has helped Lilly catch up. Broadly speaking, according to Alciati, the safety profiles of Zepbound and Wegovy are similar, with both drugs sharing common side effects like nausea and vomiting. Both products are also matched in terms of the route and frequency of administration. However, Zepbound’s “weight loss efficacy seems to be higher than Wegovy’s,” Alciati said, adding that “according to trials, there seems to be less muscle mass loss associated with Zepbound’s treatment than Wegovy’s.” Currently, Novo’s first-mover advantage and sprawling global footprint has allowed it to maintain a slight lead over Lilly. Last year, the Danish pharma logged roughly $26 billion in sales for Ozempic and Wegovy worldwide, while Lilly’s tirzepatide franchise brought in nearly $16.5 billion globally. But with an aggressive commercial strategy, Lilly is quickly gaining ground. “Eli Lilly’s drug has now been launched in all major markets,” Alciati said. Last month, the Indianapolis pharma launched Mounjaro in India, beating Novo to tap the market of the world’s most populous country. Aside from Wegovy and Zepbound, pharma has witnessed many other dramatic drug rivalries play out over the years, from Keytruda’s comeback and subsequent dominance over Opdivo and the burgeoning competition between Leqembi and Kisunla. In this article, BioSpace looks at some of the biggest pharma face-offs. Cancer: Merck’s Keytruda vs BMS’ Opdivo In the oncology arena, few drugs can hope to stand up against Merck’s blockbuster PD-1 inhibitor Keytruda, which has become a cornerstone of cancer care since its first approval in September 2014. As of writing, Keytruda has more than 41 approvals under its belt. These include several forms of melanoma, hepatocellular carcinoma, breast cancer and, crucially, lung cancer. For the last two years, it has also been the pharma’s top-selling product , bringing in $29.5 billion in 2024. But it wasn’t always that way. Keytruda once played second fiddle to Bristol Myers Squibb’s PD-1 blocker Opdivo. Approved in December 2014, just months behind Keytruda, Opdivo initially took a sizeable lead in the market, bringing in $942 million in 2015 versus Keytruda’s $566 million. “Initially, Bristol Myers Squibb was dominating that race,” William Blair partner Matt Phipps told BioSpace in an interview last month. “They had broader approvals and bigger indications.” Merck, according to Phipps, “completely overtook” BMS due to better trials and crucial approvals in lung cancer. Opdivo never recovered. Last year, the drug brought in $9.3 billion —less than a third of Keytruda’s sales. Still, BMS continues to carve out a cancer niche for Opdivo. In January, BMS won the race to bring a subcutaneous PD-1 treatment to the market, with the FDA signing off on a new formulation of Opdivo that can be delivered with an injection under the skin. Merck’s application for subcutaneous Keytruda is still under review. Meanwhile, an NSCLC approval in October 2024 made Opdivo the first PD-1 blocker that can be used both before and after surgery. Cardio: BMS, Pfizer’s Eliquis vs Bayer, J&J’s Xarelto Two blood thinners brought by four of the biggest pharmas are battling it out in cardiovascular disease. Bristol Myers Squibb and Pfizer’s oral anticoagulant Eliquis is the stronger competitor. Despite being approved more than a decade ago, Eliquis’ market presence continues to grow, surging 9% year-on-year to bring in $13.3 billion in 2024. Meanwhile, its closest competitor is a distant second. Though it won the FDA’s blessing a year ahead of Eliquis in 2011 , Bayer and Johnson & Johnson’s Xarelto has fallen behind its competitor in terms of market share. The drug peaked in 2021 when it earned J&J $2.44 billion in the U.S. and Bayer just over $5 billion in international markets, for a total of around $7.5 billion. Last year Bayer reported roughly $3.85 billion in international sales for Xarelto, while J&J recorded $2.37 billion in the U.S.—a total of over $6.2 billion. There are likely several reasons for why Eliquis has cleanly outperformed Xarelto, and one of them might be a question of clinical value. A 2021 study published in JAMA showed that in a Medicare population of more than 580,000 patients with atrial fibrillation, Xarelto was associated with significantly elevated risks of major ischemic or hemorrhagic events, such as fatal bleeding, as compared with Eliquis. Total mortality was also worse with Xarelto. Similarly, a 2023 study in Circulation found that Xarelto significantly heightened the risk of ischemic stroke and major bleeding versus Eliquis in patients in the Optum Clinformatics Data Mart database. There have been no well-designed and well-controlled head-to-head trials to compare the drugs. Alzheimer’s: Biogen, Eisai’s Leqembi vs Lilly’s Kisunla Decades of dispiriting clinical failures have finally produced two winners in Alzheimer’s disease. A tough market showdown has followed. In one corner is Biogen and Eisai’s embattled Leqembi and on the other is Eli Lilly’s newer challenger Kisunla. The anti-amyloid antibody Leqembi first won regulatory clearance in January 2023 under the FDA’s accelerated pathway before becoming the industry’s first fully approved Alzheimer’s therapy in July 2023. The buzz around Leqembi was strong, despite questions about the strength of the efficacy results and whether the benefits outweighed the risks. Phase III data presented in September 2022 helped revitalize the anti-amyloid theory, experts said at the time. In June 2023, an FDA advisory committee unanimously endorsed Leqembi’s full approval. Meanwhile, Kisunla’s path to approval was more fraught. In January 2023, the FDA turned down Lilly’s bid for accelerated approval, citing the need for more data from patients who had been treated for at least 12 months. The drug eventually won the regulator’s blessing in July 2024 , almost a year to the day behind Leqembi. Now, however, Leqembi’s edge doesn’t seem so large. Biogen and Eisai have struggled to get the drug off the ground and have been forced at least twice to lower their sales projection for the asset. In March, for instance, Eisai revealed that it expects Leqembi to bring in from ¥250 billion to ¥280 billion (approximately $1.7 billion to $1.9 billion) in its fiscal year 2027—a roughly 50% decline from a prior projection. For fiscal year 2024, which ends this month, the Japanese firm expects full-year sales of around $280 million for Leqembi. Lilly has already launched Kisunla in the U.S. but has yet to report sales figures. But both drugs have faced concerns about side effects called ARIA, which can signal bleeding or swelling in the brain. They have also faced slow uptake as physicians and health systems struggle to adapt to the new treatment paradigm. I&I: AbbVie’s Humira vs J&J’s Stelara Two pharma giants are duking it out in the immunology space with blockbuster drugs that are past their prime. AbbVie’s Humira was for six straight years the world’s best-selling drug. The biologic peaked in 2022 , bringing in $21.2 billion. But since losing key patent protections in 2023, its sales have declined steeply : last year, Humira made just under $9 billion . On the other hand, J&J’s Stelara never reached the same sales heights as Humira. At its peak in 2023, Stelara raked in $10.86 billion before dipping 4.6% to $10.34 billion last year. Like AbbVie’s biologic, Stelara is contending with copycat competitors. After it lost market exclusivity in 2023, several biosimilars have entered the U.S. market, including Amgen’s Wezlana and Sandoz’s Pyzchiva . Both Humira and Stelara work by tamping down the inflammatory response and share a substantial overlap in their indications, including psoriatic arthritis, plaque psoriasis, Crohn’s disease and ulcerative colitis. The specific mechanisms by which the drugs exert their therapeutic effects differ, however. Humira targets TNF-alpha, while Stelara acts on IL-12 and IL-23. All three molecules are crucial parts of the inflammatory cascade and often act synergistically, with slight differences in functionality. IL-12 and IL-23 explicitly encourage inflammation, for instance, while TNF-alpha can have both pro- and anti-inflammatory effects. In May 2021, a head-to-head study showed that despite these mechanistic nuances, Stelara and Humira are largely clinically similar. In patients with Crohn’s disease, Stelara induced a 64.9% clinical remission rate at 52 weeks, while Humira achieved a 61% remission rate at the same time point—a difference that failed to reach statistical significance. Lymphoma: AstraZeneca’s Calquence vs AbbVie’s, J&J’s Imbruvica The blood cancer field is witness to a BTK inhibitor battle between AbbVie and J&J’s Imbruvica, the first-comer, and AstraZeneca’s Calquence, which entered the ring four years later. The bad blood between the two goes way back to the biotech days, when Pharmacyclics developed what would become Imbruvica and rival Acerta Pharma championed Calquence. The rivalry was chronicled in Nathan Vardi’s book For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug . Both drugs work by blocking the Bruton’s tyrosine kinase, an enzyme that plays a crucial signaling role in the proliferation and activity of B cells. Because they share a mechanism of action, the two products also have wide overlap in their indications. Imbruvica and Calquence are both approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). Currently, Imbruvica has a slight edge. Last year, AbbVie reported nearly $3.35 billion in worldwide sales for the drug, as opposed to Calquence’s $3.13 billion. Imbruvica also has broader coverage: Aside from the indications that it shares with Calquence, it is also approved for chronic graft versus host disease and the rare blood cancer Waldenström’s macroglobulinemia. But Calquence is quickly gaining ground. In 2024, AstraZeneca’s asset grew 24% year-on-year, while Imbruvica slid 6.9%. Calquence is also catching up clinically. A May 2024 readout showed that AstraZeneca’s drug, when combined with standard chemoimmunotherapy, can boost progression-free survival in untreated patients with mantle cell lymphoma (MCL). AbbVie and J&J had pulled Imbruvica’s accelerated approval in this indication nearly a year before. Calquence remains approved for MCL under the FDA’s accelerated pathway. Meanwhile, real-world data presented at the 2024 Congress of the European Hematology Association showed that patients with CLL or SLL who were treated with Calquence had longer time to discontinuation or death than comparators on Imbruvica. Time to next treatment was also longer in the Calquence group, as reported by OncLive at the time.