2015年1月23日，美国FDA宣布批准Natpara（甲状旁腺激素）用于控制甲状旁腺功能减退患者的低血钙症（血钙水平低）。在美国约有6万人患有这种罕见疾病。
甲状旁腺激素协助调节体内的钙、磷水平，当甲状旁腺激素分泌异常以致激素水平过低时，即发生甲状旁腺功能减退症。
甲状旁腺功能减退症由甲状旁腺功能丧失引起，常在甲状旁腺切除手术后发生，很少由自身免疫或先天性疾病引起。甲状旁腺功能减退症患者因为血钙水平低，可出现麻木、刺痛、肌肉颤搐、肌痉挛或肌抽筋、心律异常，以及癫痫。
甲状旁腺功能减退症还与肾衰、肾结石、出现白内障及软组织钙化等长期并发症相关。
Natpara是一种甲状旁腺激素注射剂，一天注射一次，可帮助调节体内的钙水平。FDA因Natpara用于治疗罕见疾病而授予其孤儿药资格。
FDA药物评价与研究中心代谢与内分泌产品部门主任、医学博士Guettier称，“甲状旁腺功能减退症患者的治疗选择有限，但该疾病的各种症状可严重影响患者的生命质量。Natpara为不能通过钙补充剂及活性形式维生素D来控制体内钙水平的患者提供了一种替代选择。”
Natpara的安全性及有效性在一项纳入124名参与者的临床试验中得到评估，参与者随机分配至给予Natpara或安慰剂治疗。试验旨在确定Natpara是否可以作为活性形式维生素D或口服钙补充剂的替代品，或用来减少活性形式维生素D或口服钙的用量。
结果显示，Natpara治疗组有42%的参与者在减少钙补充剂及活性形式维生素D剂量的情况下达到了正常血钙水平，而安慰剂治疗组的这一比例为3%。
Natpara带有一项黑框警告，已在Natpara大鼠试验中观察到骨癌（骨肉瘤）的发生。目前尚不清楚Natpara是否会在人体内引起骨肉瘤，但由于潜在的骨肉瘤风险，Natpara仅被推荐用于不能通过钙补充剂及活性形式维生素D来控制低血钙症的患者，以及使用Natpara后潜在收益大于潜在风险的患者。
Natpara治疗的最常见不良反应包括，酸麻感、搔痒、刺痛感或皮肤灼热、低血钙、头痛、高血钙和恶心。Natpara由位于美国NPS制药公司生产。
New Drugs Online Report for parathyroid hormone
Information
Generic Name: parathyroid hormone
Trade Name: Preotact (EU), Natpara (US)
Synonym: NPSP558
Entry Type: Licence extension / variation
Development and Regulatory status
UK: Pre-registration (Filed)
EU: Pre-registration (Filed)
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Jan 15: The FDA has approved Natpar® in Hypoparathyroidism. [15]
26/01/2015 11:56:07
Dec 14: European Medicines Agency validates marketing authorisation application for Natpar® in Hypoparathyroidism [14].
03/12/2014 09:44:09
Oct 14: The FDA have postponed their final decision to Jan. 24, 2015. [13]
27/10/2014 09:48:41
Sept 14: FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 8-5 that the available data support the approval of the drug for the long-term treatment of hypoparathyroidism. US FDA decision due 24/10/14. [12]
16/09/2014 10:46:04
Jul 14: Marketing authorisation for osteoporosis withdrawn at the request of the manufacturer [11].
10/07/2014 15:12:40
Jan 14: Granted orphan drug status in the EU for the treatment of hypoparathyroidism [9].
08/01/2014 08:48:22
Oct 13: Filed in the US[8]
28/10/2013 14:29:26
Sep 12: Filing in the US now expected mid-2013. The delay is due to the Medical Device Division of FDA asking the company to modify the instructions for using the injection pen device to deliver Natpara which require Usability Testing using the modified instructions to be repeated before filing [7].
11/09/2012 09:05:31
Orphan drug status in US [1]
04/01/2011 11:31:01
Trial or other data
Nov 11: Positive top-line data from Phase III REPLACE 28-week study. The primary efficacy endpoint was defined as a 50% or greater reduction in oral calcium supplementation and active vitamin D therapy and a total serum calcium concentration that was normalised or maintained vs. baseline after 24 weeks of treatment. In an intent-to-treat analysis, 53% (48/90) of NPSP 558-treated patients achieved the main outcome vs. 2% (1/44) of placebo-treated patients. At week 24, 43% (36/84) of patients treated with NPSP 558 were able to achieve independence from active vitamin D therapy and a calcium supplementation dose of 500 mg/day or less, vs. 5% (2/37) for patients treated with placebo. 13/134 pts discontinued early, 7 were placebo-treated and 6 were NPSP 558 treated. Overall, the incidence of adverse events and serious adverse event were similar among both groups. [5]
07/11/2011 17:03:15
March 11: Last patient randomised in the REPLACE trial. A total of 135 patients were randomised in this study. [4]
03/03/2011 08:57:26
Feb 11: NCT01297309 (RACE) is a 12-month open-label extension study investigating the safety and tolerability of NPSP558 for the treatment of 40 adults with hypoparathyroidism. The primary outcome measures are: a reduction in oral calcium or an oral calcium dose of ≤500mg; a reduction in oral calcitriol to ≤0.25mcg; and an albumin-corrected total serum calcium concentration that is normalized or maintained vs baseline value (≥7.5mg/dL) and ULN, all measured after 52 weeks of treatment & 4 weeks of follow-up. The study will start in Apr 11 and is due to complete Jan 13 [3].
22/02/2011 10:06:41
Dec 10: NCT01268098 is a randomized, dose-blinded study to investigate the safety and efficacy of NPSP558 at fixed doses of 25 and 50µg in 40 adults with hypoparathyroidism. Primary outcome is a reduction in oral calcium supplementation to ≤500 mg/day, a reduction in calcitriol dose to ≤0.25 µg/day, and an albumin-corrected total serum calcium level between 7.5mg/dL and the upper limit of normal at 8 weeks. All patients will inject NPSP558 25 or 50 mcg SC once daily into alternating thighs in the morning via a multidose injection pen device. The study will start in Jan 11 and complete Dec 11 [2].
04/01/2011 11:31:47
In December 2008, the PIII REPLACE trial (NCT00732615) started, eva luating once-daily subcutaneous doses of NPSP 558 at 50, 75 or 100μg vs placebo n 110 adult patients with hypoparathyroidism. The study had a maximum 10-week screening and stabilisation period, followed by a 24-week treatment period. Effiacy is determined by a reduction in calcium and vitamin D supplementation. The trial is being conducted in the US, Canada and Europe and is expected to complete Aug 2011 [1].
04/01/2011 11:31:13
References
Available only to registered users
Category
BNF Category: Drugs affecting bone metabolism (06.06)
Pharmacology: Recombinant human parathyroid hormone-1-84
Epidemiology: This is a rare disorder. Found equally in males and females [10].
Indication: Hypoparathyroidism
Method(s) of Administration
Subcutaneous
Company Information
Name: Nycomed
US Name: NPS Pharmaceuticals
Further Information
Anticipated Commissioning route (England) -
In timetable: -
PbR Awaiting Update |
