Drugs R D. 2003;4(4):231-5. doi: 10.2165/00126839-200304040-00003.
ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with Parathyroid Hormone; TOP) has been designed to assess the bone-building and fracture-reducing potential of the drug, and over 2600 postmenopausal women with osteoporosis who have not received previous drug therapy for osteoporosis have been enrolled. Treatment will be completed in September 2003, but more than 75% of patients enrolled in the TOP study have chosen to enrol in an Open Label Extension Study (OLES), which allows for a total treatment period of up to 24 months. NPS Pharmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. In September 2002, NPS Pharmaceuticals announced that it has met its patient enrolment target (n > 150) for its POWER (PTH for Osteoporotic Women on Estrogen Replacement) study; a 24-month phase III trial initiated in Europe in November 2001. In this trial, women with osteoporosis receive SC injections of ALX 111 or placebo, in combination with their existing hormone replacement therapies, to test the bone building potential of the drug. In addition to the POWER study, a clinical trial sponsored by the National Institutes of Health (NIH) is being conducted to evaluate the potential of ALX 111 to build bone in combination with another osteoporosis medication. The 'PaTH' study (PTH/alendronate) is designed to assess the effect of various combinations and sequential uses of ALX 111 and Merck's Fosamax, a drug for slowing the loss of bone due to osteoporosis. The PaTH study, initiated in May 2000 and scheduled to conclude in September 2003, involved 238 patients with postmenopausal osteoporosis. It is thought that alendronic acid and ALX 111, when administered in combination, may act in an additive manner to treat osteoporosis because they act in different ways; alendronic acid acts to inhibit resorption and ALX 111 speeds up bone formation and resorption, with a net increase in formation. Results of this study are still being analysed but preliminary results appear to be positive. The effect of ALX 111 on bone cell cultures underare still being analysed but preliminary results appear to be positive. The effect of ALX 111 on bone cell cultures under conditions of microgravity was tested in orbit on the Space Shuttle Columbia, which was launched on 16 January 2003 but did not survive re-entry. This study was one in a series of studies known as 'OSTEO' and had been prepared by researchers from NPS Pharmaceuticals using Millenium Biologix' OSTEO Mini-Lab System. Under space flight conditions, astronauts experience a loss in bone density at a rate up to ten times faster than that of earth-bound patients with osteoporosis, and it was hoped that this study would indicate the mechanism of action of ALX 111 at cellular and genetic levels. The results of these studies were represented by the samples of human bone cells, which were lost during the re-entry tragedy.
ALX 111[甲状旁腺激素(1 - 84)-NPS Allelix，重组人甲状旁腺激素，rhPTH(1 - 84)，PREOS]是一种全长重组人甲状旁腺激素。因其具有刺激骨形成的特性，故有作为抗骨质疏松药物的潜力。此简介摘自研发洞察，这是阿迪斯国际有限公司制作的一个药学情报数据库。推荐ALX 111给药1至2年，且可与抗吸收剂如雌激素或双膦酸盐联合使用。1999年12月，Allelix生物制药公司与NPS制药公司合并。合并后的公司在美国以NPS制药公司运营，在加拿大以NPS Allelix运营。此次合并使得ALX 111在美国、欧洲和南美洲开始了III期研究。NPS制药公司已与生物成像技术公司签署协议，该公司将为此次试验提供所有图像处理和分析。1994年前，加拿大的Allelix生物制药公司和葛兰素公司参与了一项合资企业，以研究ALX 111在骨质疏松症中的疗效。随后，直到1998年9月，Allelix与瑞典的阿斯特拉公司合作开发ALX 111。阿斯特拉公司获得了ALX 111在全球的独家权利，并负责该药物的研发。然而，由于其与捷利康合并组成阿斯利康，阿斯特拉将ALX 111的所有权利归还给了Allelix。1999年12月，Allelix生物制药公司与NPS制药公司合并。合并后的公司在美国以NPS制药公司运营，在加拿大以NPS Allelix运营。此次合并使得ALX 111在美国、欧洲和南美洲开始了III期研究。ALX 111治疗骨质疏松症的III期试验已完成患者入组，II期试验已在加拿大和荷兰完成。这项为期18个月的III期多中心、安慰剂对照试验(甲状旁腺激素治疗骨质疏松症；TOP)旨在评估该药物的促骨生成和减少骨折的潜力，已招募了2600多名未接受过骨质疏松症药物治疗的绝经后骨质疏松症女性。治疗将于2003年9月完成，但参与TOP研究的患者中超过75%选择参加开放标签扩展研究(OLES)，该研究允许总治疗期长达24个月。NPS制药公司已与生物成像技术公司签署协议，该公司将为此次试验提供所有图像处理和分析。2002年9月，NPS制药公司宣布其针对POWER(雌激素替代治疗的骨质疏松症女性的PTH)研究已达到患者入组目标(n>150)；这是一项于2001年11月在欧洲启动的为期24个月的III期试验。在该试验中，患有骨质疏松症的女性接受皮下注射ALX 111或安慰剂，并结合其现有的激素替代疗法，以测试该药物的促骨生成潜力。除了POWER研究外，美国国立卫生研究院(NIH)赞助的一项临床试验正在进行，以评估ALX 111与另一种骨质疏松症药物联合使用时促骨生成的潜力。“PaTH”研究(PTH/阿仑膦酸盐)旨在评估ALX 111与默克公司的福善美(一种用于减缓因骨质疏松症导致的骨质流失的药物)的各种联合使用和序贯使用的效果。PaTH研究于2000年5月启动，计划于2003年9月结束，涉及238名绝经后骨质疏松症患者。据认为，阿仑膦酸和ALX 111联合使用时可能以相加方式治疗骨质疏松症，因为它们作用方式不同；阿仑膦酸作用于抑制吸收，而ALX 111加速骨形成和吸收，净形成增加。该研究结果仍在分析中，但初步结果似乎是积极的。ALX 111对微重力条件下骨细胞培养的影响仍在分析中，但初步结果似乎是积极的。2003年1月16日发射但在重返大气层时未能幸存的哥伦比亚号航天飞机在轨道上对ALX 111在微重力条件下对骨细胞培养的影响进行了测试。这项研究是一系列名为“OSTEO”的研究之一，由NPS制药公司的研究人员使用Millenium Biologix的OSTEO微型实验室系统进行准备。在太空飞行条件下，宇航员骨密度损失的速度比患有骨质疏松症的地面患者快多达10倍，人们希望这项研究能在细胞和基因水平上揭示ALX 111的作用机制。这些研究的结果由在重返大气层悲剧中丢失了的人骨细胞样本代表。
