University of Iowa

1 Columbia University Medical Center New York, New York 2 Brigham and Women's Hospital Boston, Massachusetts 8 University of Kansas Medical Center Kansas City, Kansas 10 University of Pennsylvania Philadelphia, Pennsylvania 11 University of Virginia Health System Charlottesville, Virginia 13 Vanderbilt University Medical Center Nashville, Tennessee 14 Indiana University Medical Center Indianapolis, Indiana 17 Mayo Clinic Rochester, Minnesota 18 National Institutes of Health Bethesda, Maryland 20 Stanford University School of Medicine Stanford, California 25 The State University of New York at Buffalo Buffalo, New York 28 VA San Diego Healthcare System San Diego, California 32 Massachusetts General Hospital Boston, Massachusetts 33 University of Maryland Medical System Baltimore, Maryland 36 University of Southern California Los Angeles, California 37 Temple University Philadelphia, Pennsylvania 38 Ernest Orlando Lawrence Berkeley National Laboratory Berkeley, California 40 Emory University Atlanta, Georgia 41 University of California, Los Angeles - UCLA Los Angeles, California 42 Johns Hopkins Medical Institutions Baltimore, Maryland 44 The University of Texas Southwestern Medical Center Dallas, Texas 45 The University of Michigan Medical School Ann Arbor, Michigan 46 University of Texas Medical Branch Galveston, Texas 47 University of California, San Diego San Diego, California 48 The University of Iowa Iowa City, Iowa 51 The Methodist Hospital DBA (doing business as) "Houston Methodist" Houston, Texas 56 University of Texas Health Science Center at San Antonio San Antonio, Texas 59 Loma Linda University Medical Center Loma Linda, California 62 VA Greater Los Angeles Healthcare System Los Angeles, California 63 University of Alabama at Birmingham Birmingham, Alabama 70 Thomas Jefferson University Philadelphia, Pennsylvania 71 University of California, San Francisco San Francisco, California 78 University of Utah Salt Lake City, Utah 91 University of Wisconsin School of Medicine and Public Health Madison, Wisconsin 92 University of California - Davis Medical Center Sacramento, California 101 NYU Langone Health New York, New York 103 North Shore University Hospital Manhasset, New York 105 Memorial Sloan-Kettering Cancer Center New York, New York 122 Washington University School of Medicine St. Louis, Missouri 125 Corewell Health (formally Beaumont Health) Royal Oak, Michigan 135 University of Colorado Anschutz Medical Campus Aurora, Colorado 145 University of Minnesota Minneapolis, Minnesota 160 State University of New York at Stony Brook Stony Brook, New York 161 University of Pittsburgh Pittsburgh, Pennsylvania 170 University of Tennessee Medical Center Knoxville, Tennessee 175 Wake Forest University Health Sciences Winston Salem, North Carolina 179 Louisiana State University Health Sciences Center in Shreveport Shreveport, Louisiana 184 The University of Washington Seattle, Washington 185 West Virginia University Hospitals Inc. Morgantown, West Virginia 186 Karmanos Cancer Institute (KCI) Detroit, Michigan 201 Banner University Medical Center - Phoenix (BUMCP)/ Banner Alzheimer's Institute (BAI) Phoenix, Arizona 202 University of North Carolina at Chapel Hill Chapel Hill, North Carolina 203 Tennessee Valley Healthcare System (Nashville VA Medical Center) Nashville, Tennessee 206 Yale University New Haven, Connecticut 207 Medical College of Wisconsin Milwaukee, Wisconsin 208 BAMF (Bold Advanced Medical Future) Health Grand Rapids, Michigan Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

5月18日（当地时间），Applied Therapeutics宣布其AKR1B1抑制剂(醛糖还原酶抑制剂)Govorestat治疗SORD缺乏症（山梨醇脱氢酶缺乏症，为腓骨肌萎缩症一种亚型）的2/3期临床研究（INSPIRE）12个月完整结果及18、24月顶线结果将在2025年周围神经学会（PNS）口头汇报。INSPIRE研究为旨在评估Govorestat治疗CMT-SORD患者有效性和安全性的随机、双盲、安慰剂对照的2/3期临床研究。56例CMT-SORD患者以2：1的比例随机接受每日一次Govorestat或安慰剂治疗。主要临床终点是12 个月时的10米步行跑步测试 （10MWRT），该测试不再包含在CMT-FOM（腓骨肌萎缩症相关测评量表）综合评分中。其他关键试验目标包括血液山梨醇水平影响、山梨醇水平与临床结果的相关性以及CMT-健康指数 （HI）。1、12月研究完整结果：对截止2024年2月的49例患者进行重新中期分析：山梨醇浓度绝对降低与10MWRT （p=0.031） 和CMT-FOM下肢结构域 （10MWRT、6MWT、爬楼梯、背屈、坐立） （p=0.037） 的变化之间存在统计学显著相关性。主要终点10MWRT无统计学意义 （p=0.457）。不过自INSPIRE研究开始以来，10MWRT已从CMT-FOM中删除，现在CMT-FOM仅由 11个部分组成。12个月时显示关键次要终点CMT-HI统计学显著改善 （p=0.039）。12个月时山梨醇变化百分比与CMT-HI变化之间的总分以及活动度和平衡领域之间存在统计学上显著相关性。血液山梨醇水平具有统计学意义的降低 （p<0.001）；总体上仍然安全且耐受性良好，组间的不良事件发生率相似。2、18和24月顶线结果：截至2024年10月11日，分别有24和15例名患者接受18个月和24个月评估。接受Govorestat持续治疗18个月和24个月顶线结果如下：24个月时MRI显示Govorestat治疗延缓疾病进展。结果改善维持24个月，包括在第12个月时CMT-HI的变化。18个月和 24个月山梨醇维持减少。24个月总体上保持安全且耐受性良好。CMT-SORD是一种罕见的进行性神经肌肉疾病，由山梨醇脱氢酶的基因突变引起，山梨醇脱氢酶负责山梨醇的代谢。在2020年之前，患者症状诊断为遗传原因不明的2型CMT或远端遗传性运动神经病变。在2020年进行全基因组测序计划后，CMT-SORD被确定为CMT（腓骨肌萎缩症）的一种亚型。Govorestat（AT-007，CAS：2170729-29-8）是一种具有中枢神经系统（CNS）渗透性的醛糖还原酶抑制剂，目前正被开发用于治疗几种罕见的神经系统疾病，包括经典型GAL、SORD缺乏症和磷酸甘露糖变位酶2-先天性糖基化障碍（PMM2-CDG）。FDA曾授予GAL孤儿药资格、儿科罕见病资格和快速通道资格，EMA授予GAL和SORD缺乏症两个适应症孤儿药资格。2024年11月，其治疗经典型半乳糖血症（GAL）的NDA被FDA拒绝，识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

Novo Nordisk presented positive findings from a late-stage basket study of once-weekly Sogroya (somapacitan) at the joint congress of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) on Monday, bolstering the growth hormone analogue’s label expansion filings in the US and EU for certain paediatric growth disorders.Specifically, Sogroya demonstrated clinical non-inferiority to once-daily Norditropin (somatropin) in pre-pubertal children born small for gestational age (SGA), or with Noonan syndrome (NS), or idiopathic short stature (ISS). The drug also showed superiority over Norditropin in children with NS and against lower doses of Norditropin in children born SGA.Highlighting the cumulative negative impact of regularly missing doses of growth hormone, Martin Lange, Novo’s executive VP for development, said: “​We are committed to providing…therapies with flexibility in administration timing and missed doses, which may better suit the needs of children with growth failure.”The Phase III REAL8 trial — part of the broader REAL programme — employed a basket design to evaluate once-weekly Sogroya across four paediatric growth disorders — SGA, NS, ISS and Turner syndrome (TS). Children with NS, TS, or ISS were randomised to receive either weekly Sogroya or daily Norditropin, while those with SGA were assigned to Sogroya, or two different Norditropin doses — lower and higher than the standard dose.Results showed the study achieved its primary endpoints across three indications. In children born SGA, Sogroya demonstrated superior estimated mean height velocity compared with a lower dose of Norditropin (11.0 vs 9.4 cm/year) and non-inferior results compared with a higher dose (11.0 vs 11.1 cm/year). In children with NS, Sogroya showed superior results (10.4 vs 9.2 cm/year), while in those with ISS, it demonstrated non-inferiority (10.5 vs 10.5 cm/year) compared with Norditropin.Meanwhile, the weekly therapy showed no safety and tolerability issues compared with the daily formulation, with similar insulin-like growth factor 1 responses observed across treatment groups. Novo noted that based on the data from REAL8 and another ongoing study REAL9, it submitted marketing applications with the FDA and the EMA for the three indications last month. Results from the TS participants are expected later this year.Sogroya is currently approved to treat growth failure due to inadequate secretion of endogenous growth hormone in children aged 2.5 years and above and as a replacement for endogenous growth hormone in adults with growth hormone deficiency.