Oral Octreotide Capsules and Paltusotine in Management of Acromegaly.

TouchREVIEWS in endocrinology Pub Date : 2024-04-01 Epub Date: 2023-11-08 DOI:10.17925/EE.2023.20.1.3
David S McLaren, Khyatisha Seejore, Julie Lynch, Robert D Murray
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引用次数: 0

Abstract

Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.

口服奥曲肽胶囊和帕曲肽治疗肢端肥大症。
注射用体生长抑素受体配体(iSRL)是肢端肥大症患者最常用的药物疗法,但满意率却不尽如人意。注射会导致局部红斑、不适和皮下结节的形成,每 4 周还需前往初级或二级医疗机构进行注射,十分不便。一些患者还注意到,在注射周期即将结束时,与肢端肥大症相关的症状会有所突破。为了提高这些患者的接受度并最终改善他们的健康状况,我们开发了两种口服SRL,即口服奥曲肽胶囊(OOC)和帕妥索汀。口服奥曲肽胶囊结合了肠溶衣和瞬时渗透增强剂,前者可将奥曲肽输送到小肠,后者可提高口服生物利用度。每天两次的 OOC 和皮下注射奥曲肽 100 µg 可获得相似的奥曲肽水平。III 期研究显示,在之前接受稳定剂量 iSRL 治疗的患者中,至少有 60% 的患者使用 OOC 可维持同等的生化控制。在长期研究中,对 OOC 的反应可持续 3 年之久。Paltusotine 是一种新型强效口服非肽基体生长抑素受体亚型-2 配体。对健康志愿者的研究显示,该药对生长激素释放激素诱导的生长激素分泌和胰岛素样生长因子-I(IGF-I)的抑制与重复剂量有关。在最近的 II 期研究中,对 iSRL 单药治疗部分应答(IGF-I 为正常值上限的 1.0 - 2.5 倍)的肢端肥大症患者在改用每日一次的帕曲托汀治疗 13 周后,87% 的患者的 IGF-I 控制在基线的 20% 或更低水平。OOC和帕妥索汀的不良反应与iSRL的不良反应相似,发生频率也相似。在治疗肢端肥大症的药物疗法中,OOC和帕妥索汀是备受欢迎的新药;然而,还需要更多有关疗效、肿瘤控制和缩小的数据,才能将这种药物纳入肢端肥大症的治疗方案中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
2.40
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