SHP-610(SHP-610) - 药物靶点：HS_专利_临床

概要

基本信息

药物类型

酶

别名

Recombinant human heparan N-sulfatase、rhHNS、HGT-1410

+ [2]

靶点

HS

作用方式-

作用机制

硫酸乙酰肝素硫酸酯酶替代物

治疗领域

遗传病与畸形内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

黏多醣贮积症III型

原研机构

Shire Plc

在研机构-

非在研机构

Shire Plc

权益机构-

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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关联

2

项与 SHP-610 相关的临床试验

NCT02350816

/ Terminated临床2期

An Open-Label Extension of Study HGT-SAN-093 Evaluating the Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Mucopolysaccharidosis Type IIIA Disease

This extension study will allow participants to continue receiving treatment with HGT-1410 and to initiate treatment in patients who received no-treatment in Study HGT-SAN-093, and will evaluate the long-term safety and efficacy of the study drug.

开始日期2015-04-08

申办/合作机构

Shire Plc

NCT02060526

/ Completed临床2期

A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of rhHNS (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Early Stage Mucopolysaccharidosis Type IIIA Disease

Sanfilippo syndrome Type A, or Mucopolysaccharidosis (MPS) IIIA, is a rare lysosomal storage disease caused by deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, there is an accumulation of the glycosaminoglycan, heparan sulfate, resulting in progressive neurodegeneration. Symptoms are usually first noted in the 1st or 2nd year of life, although definitive diagnosis is often delayed, with an average age of diagnosis of 4.5 years. The disease is characterized by developmental delays initially, followed by neurological developmental arrest, then regression. These developmental deficits are typically associated with severe behavioral disturbances. Patients have a significantly reduced lifespan, with few surviving beyond the 2nd or 3rd decade.
The purpose of this study is to evaluate the safety and efficacy of recombinant human heparan-N-sulfatase (rhHNS) in pediatric patients with Early Stage Mucopolysaccharidosis Type III A Disease.

开始日期2014-02-26

申办/合作机构

Shire Plc

100 项与 SHP-610 相关的临床结果

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100 项与 SHP-610 相关的转化医学

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100 项与 SHP-610 相关的专利（医药）

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5

项与 SHP-610 相关的文献（医药）

2021-12-01·Molecular genetics and metabolism2区 · 生物学

Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A

2区 · 生物学

Article

作者: Marchal, Jan Pieter ; Wijburg, Frits A ; Nestrasil, Igor ; Shapiro, Elsa ; Alexanderian, David ; de Ruijter, Jessica ; Tump, Evelien ; Rust, Stewart ; Heap, Fiona ; Jones, Simon A

INTRODUCTION:

Currently, there is no effective therapy for mucopolysaccharidosis IIIA (MPS IIIA). Intravenously-administered enzyme replacement therapies, while effective in other forms of MPS without neurological involvement, have not been successful in patients with MPS IIIA, as they are unable to cross the blood-brain barrier to improve neurological symptoms. We evaluated the long-term safety, tolerability, and clinical outcomes of recombinant human heparan-N-sulfatase (rhHNS) administered intrathecally (IT) in children with MPS IIIA in a phase 1/2 extension study.

METHODS:

Patients aged ≥3 years with MPS IIIA who had previously completed a phase 1/2 study and received ≥5 of the 6 planned rhHNS infusions via IT administration, were eligible for inclusion. Patients who received 10 mg in the phase 1/2 study had their dose increased to 45 mg. Patients who were treated with 45 mg or 90 mg rhHNS IT in the phase 1/2 study remained on this monthly dose in the extension study. rhHNS was administered via an intrathecal drug delivery device (IDDD). Primary endpoints included the type and severity of adverse events, presence of anti-rhHNS antibodies in the CSF and serum, and changes in laboratory values. Secondary endpoints included standardized neurocognitive assessments and brain magnetic resonance imaging.

RESULTS:

In the extension study, 12 patients with a mean (SD) age of 9.6 (7.3) years continued treatment with rhHNS IT for a median of 264.4 weeks. Ten of 12 patients completed the extension study. rhHNS IT was generally well-tolerated. All patients experienced at least one treatment-emergent adverse event (TEAE), most being mild or moderate in severity. No serious adverse events (SAEs) were considered related to the study drug, and no deaths occurred. Most SAEs were related to malfunctions of the IDDD. Declines from baseline in Bayley Scales of Infant Development, Third Edition or Kaufman Assessment Battery for Children, Second Edition, Nonverbal Index developmental quotient scores were evident at all rhHNS dosing groups: -17.97%, -18.99%, and -12.12% in the 10/45, 45, and 90 mg groups, respectively, at Month 54.

CONCLUSIONS:

Overall, rhHNS IT was well tolerated in the extension study. However, rhHNS IT was unable to slow the neurocognitive decline of patients with MPS IIIA. This study was subsequently terminated early because pre-specified efficacy criteria were not met, and the study did not yield clinical proof of concept. (Clinicaltrials.gov Identifier NCT01299727).

2021-09-01·Molecular genetics and metabolism2区 · 生物学

A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A

2区 · 生物学

Article

作者: Muschol, Nicole ; Cleary, Maureen ; Wijburg, Frits A ; Alexanderian, David ; Whitley, Chester B ; Shapiro, Elsa ; Gasperini, Serena ; Del Toro, Mireia ; Sevin, Caroline ; Muenzer, Joseph

Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a rare autosomal recessive lysosomal disorder characterized by deficient heparan-N-sulfatase (HNS) activity, and subsequent accumulation of heparan sulfate, especially in the central nervous system. The disease is associated with progressive neurodegeneration in early childhood. For this open-label extension study of a phase 2b clinical trial, we report on safety and cognitive decline in patients receiving intrathecal (IT) administration of recombinant human HNS (rhHNS). Of 21 patients who completed the phase 2b study, 17 continued in the open-label extension. Patients receiving rhHNS IT 45 mg continued to receive the same treatment regimen (i.e., every 2 weeks or every 4 weeks) throughout the extension. Patients receiving no treatment in the phase 2b study were re-randomized to the treatment groups. Neurocognition was assessed using the Bayley Scales of Infant and Toddler Development®, Third Edition (BSID-III). Adverse events were recorded over the duration of the treatment period. Cognitive decline was observed in most patients in both treatment groups; however, improvements in BSID-III development quotient score were observed for two patients, in receptive and expressive communication scores for three patients each, in fine motor skills for one patient, and in gross motor skills for six patients. Treatment-emergent adverse events that occurred with rhHNS IT were mostly mild, none led to study discontinuation, and there were no deaths. The extension study was terminated early as the primary endpoints of the phase 2b study were not met, and no statistical analyses were carried out. Although cognitive decline was apparent in most patients, improvements were observed in a small group of patients. Greater declines were observed in patients at the higher end of the age range, suggesting earlier intervention may increase the possibility of a response to treatment. rhHNS IT treatment remained generally well tolerated up to 96 weeks.

2019-02-01·Molecular genetics and metabolism

Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial

Article

作者: Muschol, Nicole ; Cleary, Maureen ; Wijburg, Frits A ; Shapiro, Elsa ; Kerr, Douglas ; Whitley, Chester B ; Gasperini, Serena ; Del Toro, Mireia ; Sevin, Caroline ; Muenzer, Joseph ; Alexanderian, David ; Bhargava, Parul

BACKGROUND:

Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate in the central nervous system and is associated with progressive neurodegeneration in early childhood. We report on the efficacy, pharmacokinetics, safety, and tolerability of intrathecal (IT) administration of recombinant human HNS (rhHNS) from a phase IIb randomized open-label trial.

METHODS:

Twenty-one patients, randomized 1:1:1 to rhHNS IT 45 mg administered every 2 weeks (Q2W), every 4 weeks (Q4W), or no treatment, were assessed for amelioration in neurocognitive decline as determined by the Bayley Scales of Infant and Toddler Development®, Third Edition. The primary efficacy goal was defined as ≤10-point decline (responder) in at least three patients in a dosing cohort after 48 weeks. Other efficacy assessments included adaptive behavioral function, assessments of cortical gray matter volume, and glycosaminoglycan (GAG) levels in urine.

RESULTS:

A clinical response to rhHNS IT was observed in three treated patients (two in the Q2W group, one in the Q4W group). Cerebrospinal fluid heparan sulfate and urine GAG levels were reduced in all treated patients. However, most secondary efficacy assessments were similar between treated patients (n = 14; age, 17.8-47.8 months) and untreated controls (n = 7; age, 12.6-45.0 months). Treatment-emergent adverse events that occurred with rhHNS IT were mostly mild, none led to study discontinuation, and there were no deaths.

CONCLUSION:

rhHNS IT treatment reduced heparan sulfate and GAG levels in treated patients. Though the primary neurocognitive endpoint was not met, important lessons in the design and endpoints for evaluation of cognitive and behavioral diseases resulted.

TRIAL REGISTRATION:

ClinicalTrials.govNCT02060526; EudraCT 2013-003450-24.

1

项与 SHP-610 相关的新闻（医药）

2016-11-01

·BioSpace

In 3Q Report, Shire Breaks Out Data From Baxalta Acquisition and Announces Several Program Terminations

November 1, 2016 By Mark Terry , BioSpace.com Breaking News Staff Third-quarter financial reports show how companies are doing going into the end of the year. And this year, at least, they show a number of biopharma companies killing programs. Biogen announced in its third-quarter report that it was ending development of MT-1303 for various immune disorders like multiple sclerosis (MS), and Crohn’s disease. Pfizer announced today that it was ending its PCSK9 cholesterol program. And Shire reported that it was terminating its SHP610 program for Sanfilippo A after a failed Phase IIb study. In its third-quarter report, Shire stated, “The Phase IIb study of SHP610 in pediatric patients with early stage Sanfilippo A did not meet its primary endpoint of slowing the cognitive decline in patients. Shire intends to terminate all clinical trials of SHP610 and plans to publish the results of the SHP610 program for the benefit of the San Filippo community.” It also indicated that as of October 21, Shire was terminating a deal with CTI BioPharma Corp. and returning all rights related to pacritnib to CTI. It also ended relationships with SFJ Pharmaceuticals and its biosimilar collaboration with Coherus Biosciences . “Additionally,” the company said, “Shire has delivered notice of exercise of its right to terminate its biosimilar collaboration with Momenta Pharmaceuticals, Inc. and such termination will be effective upon expiration of the applicable termination notice period. These collaborations were acquired through the Baxalta acquisition.” Overall, Shire’s third-quarter revenues and earnings didn’t quite hit forecasts. The company didn’t raise guidance, but evidence shows that its June acquisition of Baxalta incurred higher costs than expected. Setting aside Baxalta data, Shire’s product sales grew by 12 percent. All of its legacy franchises grew during the third quarter. Both neuroscience and internal medicine grew by 15 percent. Flemming Ornskov , Shire’s chief executive officer, said in a statement, “During the third quarter, we made rapid progress integrating our new company while delivering record quarterly product sales growth and remaining on track to meet our full year Non GAAP guidance. The launch of Xiidra is off to a very strong start, and we are using this momentum to build a leadership position in pharmaceutical ophthalmics.” Xiida brought in $14 million in the third quarter. The company showed a third-quarter loss of $386.8 million, and on a per-share basis, lost $1.29. When adjusted for non-recurring costs and discontinued operations, it was $3.17 per share. According to Zacks Investment Research, nine analysts estimated an average earnings of $3.18 per share. The company’s problems seem to be more operational, than product-related. In the third quarter, it showed $3.315 billion in product sales, a growth of 110 percent. Even excluding Baxalta products, it showed $1.769 billion, a 12 percent growth for the quarter, with total revenues up 109 percent. However, its U.S. GAAP operating loss from continuing operations was $406 million in the quarter. Since the beginning of the year, Shire stock had dropped 18 percent, and 26 percent in the last 12 months. Shire is currently trading for $166.35.

临床2期并购财报临床失败上市后研究

100 项与 SHP-610 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
黏多醣贮积症III型	临床2期	美国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	阿根廷	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	法国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	德国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	意大利	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	荷兰	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	西班牙	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	英国	Shire Plc	2014-02-26

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01299727 (CTgov)	临床1/2期	黏多醣贮积症III型	12	HGT-1410 (HGT-1410/rhHNS 10 mg)	鹹憲齋夢鏇襯遞築鑰獵 = 積範鹽構獵選蓋蓋範蓋獵衊鏇齋廠簾廠繭鏇遞 (鏇窪鬱齋齋蓋築積積獵, 醖獵繭願窪選襯糧積蓋 ~ 獵製鬱膚廠顧餘艱夢繭) 更多	-	2020-04-21
				HGT-1410 (HGT-1410/rhHNS 45 mg)	鹹憲齋夢鏇襯遞築鑰獵 = 憲鬱鑰餘醖獵膚醖觸簾獵衊鏇齋廠簾廠繭鏇遞 (鏇窪鬱齋齋蓋築積積獵, 醖餘夢齋獵觸糧壓鏇簾 ~ 鏇蓋獵觸鑰鏇廠觸製鏇) 更多
NCT02350816 (CTgov)	临床2期	黏多醣贮积症III型	17	HGT+HGT-1410 (Group 1)	願鑰廠鏇簾鹽製艱夢餘 = 憲夢鹽鏇築簾鬱觸構蓋衊衊糧獵鏇鬱齋醖淵夢 (淵遞憲淵廠蓋廠淵鏇夢, 醖齋築鏇構觸鏇糧餘壓 ~ 鏇獵蓋餘鬱遞糧鹹窪蓋) 更多	-	2020-04-20
				HGT-1410 (Group 2)	願鑰廠鏇簾鹽製艱夢餘 = 餘憲糧壓願淵觸簾膚製衊衊糧獵鏇鬱齋醖淵夢 (淵遞憲淵廠蓋廠淵鏇夢, 觸鏇糧齋簾繭蓋窪遞製 ~ 壓鹹願遞遞艱蓋繭遞窪) 更多
NCT01155778 (CTgov)	临床1/2期	黏多醣贮积症III型	12	HGT-1410 (HGT-1410 10 mg)	蓋憲簾襯繭憲蓋廠夢醖 = 壓選選鏇膚襯窪憲網壓壓糧網顧蓋積糧襯遞餘 (窪襯遞顧憲製鏇觸淵觸, 壓蓋膚築衊築鏇鹽繭壓 ~ 範顧壓鏇獵襯顧齋鏇艱) 更多	-	2018-12-12
				HGT (HGT-1410 45 mg)	蓋憲簾襯繭憲蓋廠夢醖 = 蓋觸壓淵製獵願鹽糧簾壓糧網顧蓋積糧襯遞餘 (窪襯遞顧憲製鏇觸淵觸, 觸鬱鏇憲網鹹選餘廠淵 ~ 齋鑰窪顧夢鏇糧顧遞糧) 更多
NCT02060526 (CTgov)	临床2期	黏多醣贮积症III型	21	HGT-1410 (No HGT-1410)	繭齋築糧網選鬱簾餘衊 = 蓋鑰窪膚築淵積範願鏇餘簾糧製淵廠網膚顧廠 (夢醖衊齋廠範齋餘鬱蓋, 繭積積鏇膚鹹窪壓蓋壓 ~ 膚鏇壓簾壓鑰鑰選襯廠) 更多	-	2017-03-03
				HGT-1410 (HGT-1410 45 mg Q2W)	繭齋築糧網選鬱簾餘衊 = 願觸憲製襯鬱醖鏇選選餘簾糧製淵廠網膚顧廠 (夢醖衊齋廠範齋餘鬱蓋, 襯獵蓋襯衊獵遞鹹範憲 ~ 獵鬱顧製蓋遞構築製構) 更多