Hyperparathyroidism, Primary

▎药明康德内容团队编辑阿斯利康（AstraZeneca）今日宣布，已达成最终协议，拟斥资10.5亿美元收购致力于开发针对罕见内分泌疾病的创新疗法的生物技术公司Amolyt Pharma。这项拟议的收购将使阿斯利康获得名为eneboparatide（AZP-3601）的研发项目。Eneboparatide是一种处于3期临床研究的治疗性多肽，具有创新作用机制，旨在满足甲状旁腺功能减退症（hypoparathyroidism）患者的未竟医疗需求。在甲状旁腺功能减退症患者中，甲状旁腺激素（PTH）生产不足导致钙和磷的严重失调，可能导致改变生活的症状和并发症。它是已知患者人数最多的罕见病之一，约80%患者为女性。甲状旁腺功能减退症的临床表现影响许多组织和器官系统，特别是肾脏和骨骼。Eneboparatide是一种PTH受体1（PTHR1）激动剂，具有独特作用机制，它通过与PTHR1的特定构象结合，旨在满足甲状旁腺功能减退症的治疗目标。2期临床数据显示，eneboparatide实现了血清钙水平的正常化，以及可能消除患者对每日钙和维生素D补剂的依赖。在慢性甲状旁腺功能减退症和高钙尿症的成人中，结果显示eneboparatide使尿中的钙水平正常化，有助于预防慢性肾病发生。此外，eneboparatide维持了骨矿物质密度，这是为骨质疏松或骨质减少症风险增加的患者提供的一个重要潜在益处。▲Amolyt公司的研发管线（图片来源：Amolyt公司官网）Eneboparatide之外，Amolyt公司的研发管线中还包括AZP-3813，一种肢端肥大症潜在治疗方法；和AZP-40XX，潜在治疗原发性甲状旁腺功能亢进症（PHPT）和恶性肿瘤性高钙血症（HHM）的方法。根据协议条款，阿斯利康将斥资高达10.5亿美元收购Amolyt Pharma。这包括8亿美元预付款，以及基于实现特定监管里程碑时支付的2.5亿美元额外付款。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] AstraZeneca to acquire Amolyt Pharma, expanding late-stage rare disease pipeline. Retrieved March 14, 2024, from https://www.astrazeneca.com/media-centre/press-releases/2024/astrazeneca-to-acquire-amolyt.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

AstraZeneca is splashing out $800 million upfront to bolster its rare disease pipeline with the purchase of Amolyt Pharma and its Phase III asset for chronic hypoparathyroidism.Marc Dunoyer, chief executive of AstraZeneca’s rare-disease unit Alexion, noted that patients with chronic hypoparathyroidism “face a significant need for an alternative to current supportive therapies,” with Amolyt’s eneboparatide holding “the potential to lessen the often debilitating impact of low parathyroid hormone and avoid the risks of high-dose calcium supplementation.”Eneboparatide – also known as AZP-3601 – is a PTH receptor 1 agonist that in Phase II studies has shown the ability to achieve normalisation of serum calcium levels, as well as the potential to eliminate dependence on daily calcium and vitamin D supplementation. AstraZeneca noted that in adults with chronic hypoparathyroidism and hypercalciuria, eneboparatide normalised calcium in urine, while it also preserved bone mineral density.According to Amolyt’s website, its pipeline also includes AZP-3813 for acromegaly - with initial Phase I results expected later this year - and the preclinical candidate AZP-40XX for primary hyperparathyroidism and humoral hypercalcemia of malignancy.Along with the upfront payment, Amolyt shareholders are eligible to receive an additional $250 million payable upon achievement of a specified regulatory milestone. The acquisition is expected to close by the end of the third quarter.

Pictured: AstraZeneca's headquarters in Silicon Valley/iStock, Sundry Photography AstraZeneca on Thursday announced that it is acquiring rare disease specialist Amolyt Pharma in a deal that could reach $1.05 billion in value. Under the terms of the agreement, AstraZeneca will buy Amolyt’s outstanding shares for a total of $800 million, due on the deal’s closing. Amolyt will also be entitled to a contingent payment of $250 million upon meeting a yet-undisclosed regulatory milestone. The partners expect to complete the transaction in the third quarter of 2024, pending regulatory clearances and other customary closing conditions. After the acquisition is closed, Amolyt and its employees will join AstraZeneca’s rare disease unit Alexion. At the center of the acquisition is Amolyt’s late-stage candidate for the rare disease hypoparathyroidism, which is characterized by low levels of the parathyroid hormones in the blood. Patients with hypoparathyroidism also have abnormal levels of calcium and phosphorous, which can lead to complications such as kidney problems and heart failure. “Chronic hypoparathyroid patients face a significant need for an alternative to current supportive therapies, which do not address the underlying hormone deficiency,” Alexion CEO Marc Dunoyer said in a statement, adding that eneboparatide could “lessen the often-debilitating impact of low parathyroid hormone” while also avoiding the “risks of high-dose calcium supplementation.” Dubbed eneboparatide, Amolyt’s candidate for hypoparathyroidism activates the parathyroid hormone receptor 1, leading to stable and sustained calcium levels in the blood and normal calcium excretion through the urine. According to the biotech’s website, this mechanism of action allows eneboparatide to treat the symptoms of hypoparathyroidism and avoid kidney disease, while also slowly removing the need for calcium and vitamin D supplementation. Eneboparatide also helps preserve bone integrity by normalizing bone turnover levels and lowering bone resorption. In a Phase IIa study, 93% of patients who were treated with eneboparatide were able to stop standard of care treatment using calcium and vitamin D supplementation. Urinary calcium excretion also dropped to normal levels, while serum calcium levels remained within target range. Patients also showed stable bone mineral density, including those who had osteopenia. In May 2023, Amolyt announced that it had competed an end-of-Phase II meeting with the FDA and that it would launch a Phase III study of eneboparatide in hypoparathyroidism. The biotech at the time envisioned the study, dubbed Calypso, to be the largest Phase III trial to date in this indication. Top-line data are expected by the end of 2024. In addition to eneboparatide, AstraZeneca will also gain ownership of AZP-3813, which is being assessed for acromegaly with topline Phase I data expected in the first half of this year. Amolyt is also developing AZP-40XX, which is still in the very early stages of development for primary hyperparathyroidism and humoral hypercalcemia of malignancy. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.