Zilucoplan

Aside from entrenched rivals like AstraZeneca’s Ultomiris, Vyvgart is now facing pressure from a pair of myasthenia gravis biologics newcomers introduced by UCB. As argenx continues to scoop up biologics market share with its antibody fragment Vyvgart in generalized myasthenia gravis (gMG), the Dutch immunology outfit is confident that it’s “just at the beginning of the growth curve” in its inaugural indication, executives said on an analyst call Thursday. Not content to rest on its laurels, either, argenx is leveraging the commercial insights it’s garnered over the past two years as it preps for the launch of Vyvgart’s next potential approval in chronic inflammatory demyelinating polyneuropathy (CIDP), slated for an FDA decision by June 21. Argenx this morning reported 83% year-over-year and 6% quarter-over-quarter revenue growth to $398 million in the first three months of 2024. The autoimmune company’s sales currently hinge on Vyvgart and the drug’s Halozyme-partnered subcutaneous formulation Vyvgart Hytrulo, both of which are approved in gMG in the U.S. and many other countries. Vyvgart also boasts a single approval for the rare bleeding disorder immune thrombocytopenia (ITP) in Japan. The company’s sales growth this quarter reflects the “strong medical need in myasthenia gravis,” as well as the “quality” of Vyvgart and the “excellent execution” of the drug’s commercial rollout, analysts with ODDO BHF wrote in a note to clients Thursday. The analysts stuck by their thesis that the products remain well positioned to hit peak sales of $11 billion in 2035—an estimate that accounts for future indications like CIDP, too. Aside from the opportunities in gMG and CIDP, argenx also aims to broaden Vyvgart’s reach with the introduction of a prefilled syringe. The company said in an earnings release that it’s on track to submit a U.S. application for that delivery format in 2024’s second quarter. Still, Vyvgart is far from the only gMG biologic in town. Aside from entrenched rivals like AstraZeneca’s Ultomiris, Vyvgart is now facing pressure from a pair of newcomers introduced by UCB. UCB won back-to-back nods for two separate gMG therapies last year, starting with a green light for its subcutaneous monoclonal antibody Rystiggo in July. In October, the company’s med Zilbrysq—a targeted C5 inhibitor with a different mechanism of action than Rystiggo—snared FDA backing as the first subcutaneous gMG-targeted therapy patients can administer themselves, according to UCB. But despite those new challengers, argenx’s chief operating officer, Karen Massey, said the company isn’t seeing a significant impact from competition.  In fact, argenx continues to see Vyvgart’s market share grow quarter over quarter among biologics, she said during the call. She credited much of that growth to the product’s subcutaneous version, which saw a 34% uptick in U.S. patients this quarter. Massey said the company continues to see many new patient starts on Vyvgart, with more than 50% of those novel prescriptions coming from people who are switching over from an oral gMG therapy. “I think the more innovation that comes to market, the more the biologic share overall is going to grow and the more we’ll be able to help lead within that biologic share,” Massey said. “I’m very confident that we’re just at the beginning of the growth curve with MG,” the COO added. Building on Massey’s point, argenx CEO Tim Van Hauwermeiren noted on the company’s call that argenx recently kicked off a Vyvgart study in seronegative myasthenia gravis as well, which has the potential to become a label-expanding study. Roughly 15% of gMG patients are estimated to be seronegative, which could provide a meaningful addition to the drug’s current green light, the CEO said. All told, there are now more than 10,000 gMG patients on argenx’s treatment globally, the company noted (PDF) in a slide deck accompanying its earnings presentation. As for Vyvgart’s upcoming opportunity in CIDP, argenx has been busy establishing a “comprehensive launch plan” to help educate both neurologists and patients around the benefits of switching over to the med, Massey said. With the CIDP therapies on tap today—typically steroids and intravenous immunoglobulin—roughly 88% of patients still experience residual symptoms despite ongoing treatment, argenx’s research has shown. Given the drug’s successful phase 3 trial in CIDP last month and its clean safety profile, argenx figures patients and doctors will be enticed to make the switch to Vyvgart because they won’t “have to balance that trade-off between efficacy and treatment burden,” Massey said. Argenx plans to adopt the same pricing approach it used in gMG for Vyvgart’s potential green light in CIDP, including through value-based arrangements with payers, Massey said, noting access talks for that potential launch are “on track.” Since its commercial debut in late 2021, argenx has touted the potential for Vyvgart as a pipeline in a product. But while Vyvgart is faring well in many disease areas, the drug has shown its limitations in recent months, too. Alongside earnings Thursday, argenx revealed that it’s discontinuing planned development of the FcRn inhibitor in ANCA-associated vasculitis, which describes a group of rare autoimmune diseases marked by inflammation and damage to the small blood vessels. The decision comes after a risk assessment of ongoing studies following recent clinical misfires in ITP and the chronic blistering disease pemphigus.

2023年，FDA的CDER一共批准了55款新分子实体（NME）药物，其中包括6款多肽类药物，占据CDER今年批准新分子实体药物的11%，称得上大获丰收之年。多肽获批新药从治疗领域来看，抗肿瘤（一款用于治疗；一款用于肿瘤诊断）、抗感染和罕见病（Rett综合征、全身性重症肌无力）领域各2款。 · DAYBUE（trofinetide，曲非奈肽）是一种新型的IGF-1氨基末端三肽的类似物，于2023年3月被FDA批准用于治疗2岁及以上儿童的雷特综合征。这是治疗雷特综合症的里程碑式事件，在审批过程中，FDA授予了DAYBUE优先审评、孤儿药和快速通道认定的头衔。 · REZZAYO（rezafungin）是一种新型棘白菌素，通过抑制β-1,3-葡萄糖合成酶从而扰乱真菌细胞壁的完整性来发挥作用，也成为十多年来首个获得FDA批准的新棘白菌素。 · POSLUMA（flotufolastat F 18）于2023年5月25日，得到FDA监管批准，用于疑似转移的前列腺癌男性的PSMA阳性病变的PET。它是第一个获得FDA批准的采用专有放射性杂交技术开发的PSMA靶向成像剂。 · PAXLOVID由于疫情原因在2021年12月22日获得了FDA的紧急使用授权，但正式获批日期是2023年5月25日。PAXLOVID中包含两种活性成分nirmatrelvir和ritonavir，它们都是拟肽类物质，两种拟肽相得益彰，造就了Paxlovid“沧海横流，方显英雄本色”的医药史地位。 · APHEXDA（motixafortide）与非格司亭(G-CSF)联合使用，将造血干细胞动员至外周血，用于多发性骨髓瘤患者的采集和随后的自体移植。这是十年来美国批准的第一个用于治疗多发性骨髓瘤的干细胞动员创新药物。 · ZILBRYSQ（zilucoplan）获FDA批准用于治疗抗乙酰胆碱受体（AChR）抗体阳性的全身型重症肌无力（gMG）成年患者。该药是一种每日一次经皮下给药的新型大环肽类C5补体抑制剂。2019年，其被FDA授予孤儿药资格，2023年12月1日，zilucoplan获得了欧盟委员会针对gMG的批准。 Global多肽药物的优势在于其有较高的靶向性和选择性，以及相对较低的毒副作用。FDA已批准的多肽药物主要分布在7大疾病治疗领域，包括罕见病、肿瘤、糖尿病、胃肠道、免疫、心血管疾病、骨科等。 2022年全球市场销售额排名前十的多肽类药物中前八名均为糖尿病或肥胖症用药，主要以GLP-1受体激动剂为主。其中销售额最高的司美格鲁肽2022年全球销售额达到109.14亿美元，度拉糖肽以74.40亿美元紧随其后。此外，GLP-1类药物（司美格鲁肽）在糖尿病和肥胖相关的心衰（HFpEF）和慢性肾病（CKD）领域均取得优异治疗效果，并在积极拓展阿尔兹海默（AD）和非酒精性脂肪肝（NASH）等适应症。随着司美格鲁肽、度拉糖肽等GLP-1多肽药物销售快速增长，全球肽类药物市场规模有望加速扩容，迎来多肽药物的春天。 目前全球获批的多肽类药物约180种，2022年全球多肽药物市场规模达729亿美元，2023年全球多肽药物市场规模将达到795亿美元，从区域分布来看，目前美国和欧洲是多肽药物最主要的市场，其中，美国占比高达42.43%。而司美格鲁肽作为一种新型多肽药物，以其卓越的疗效和广阔的市场前景，成为了2023年的多肽“爆款”药物。 其作为诺和诺德的明星产品，在2023年共取得了212.01亿美元的销售额，其中注射液Ozempic（2型糖尿病）收入139.17亿美元，同比增长60%；片剂Rybelsus（2型糖尿病）收入27.26亿美元，同比增长66%；注射液Wegovy（肥胖）收入45.57亿美元，同比增长407%。这一成就的背后，是多肽药物行业的飞速发展和技术创新的不断突破。 Domestic中国多肽药物市场的产品结构与国际成熟市场差异显著，国内销售额较大的多肽药物主要是抗肿瘤和免疫调节类产品，与发达国家相比，中国多肽药物其他治疗领域市场份额还相对较少，随着我国鼓励创新药研发和推进仿制药一致性评价工作的政策出台，预计未来将有更多具有显著临床效果的多肽创新药和多肽仿制药获批上市，使得我国多肽药物市场进一步扩容。 我国多肽药物市场由2016年的415.8 亿元增长至2020年的595亿元，期间复合增长率达到9.37%。预计2023年中国多肽类药物市场规模将达到881亿元。 多肽创新药物的研发与生产存在较高壁垒，下游药企倾向于和专业的多肽CDMO或原料药企业合作，实现降本增效。根据弗若斯特沙利文数据，2021-2030年全球多肽CDMO市场规模有望由22亿美元增长至118亿美元，CAGR为21%；中国多肽CDMO市场规模有望从13亿元增长至185亿元，CAGR为34%。国内多肽CDMO虽然起步较晚，但凭借成本优势和技术、产能上的突破，有望赶超海外头部企业。 References参考文献 1、《GLP~1多肽药物固相合成载体和辅助材料行业分析，GLP~1多肽药物成长可期，固相载体和纯化材料有望受益-231110》，野村东方国际证券，2023.11 2、《多功能GLP-1药物引领行业发展，关注上游原料药板块》，平安证券，2023.11 内容来源于网络，如有侵权，请联系删除。