A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Pharmacodynamic Efficacy and Clinical Benefit of AT 007 in Patients with Sorbitol Dehydrogenase (SORD) Deficiency

开始日期2022-09-14

申办/合作机构

Applied Therapeutics, Inc.

NCT05397665

/ Active, not recruiting临床2/3期

A RandomIzed, Double-Blind, Placebo-CoNtrolled, Two-Part Study to Evaluate the Pharmacodynamic EffIcacy and Clinical Benefit of AT 007 in Patients With SoRbitol Dehydrogenase (SORD) DEficiency

This study is designed to assess the efficacy and safety of AT-007 treatment in patients with SORD Deficiency. This randomized, double-blind study will assess the effect of AT-007 compared to Placebo in SORD Deficiency patients for 24 months.

开始日期2022-01-01

申办/合作机构

Applied Therapeutics, Inc.

NCT05418829

/ Unknown status临床3期

An Open-Label Study to Evaluate the Long-Term Safety and Pharmacodynamic Efficacy of AT-007 in Adult Subjects With Classic Galactosemia (CG)

This study is a 12-month open-label extension (OLE) study of AT-007 in adult subjects with CG who previously participated in Study AT-007-1001 Part D and/or Part D Extension.
The study is designed to assess the long-term safety of AT-007 in subjects with CG as well as the pharmacodynamics (PD) (inhibition of galactitol) and PK of AT-007. The effect of 12-month treatment with AT-007 on the levels of galactose and other galactose metabolites in subjects with CG will also be evaluated.

开始日期2021-10-01

申办/合作机构

Applied Therapeutics, Inc.

100 项与 Govorestat 相关的临床结果

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100 项与 Govorestat 相关的转化医学

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100 项与 Govorestat 相关的专利（医药）

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项与 Govorestat 相关的文献（医药）

2024-11-01·JOURNAL OF CLINICAL PHARMACOLOGY

Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT‐007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study

Article

作者: Bailey, Evan ; Wang, Stella ; Mills, Richard ; Mohanlal, Ramon ; Perfetti, Riccardo ; Shendelman, Shoshana

Abstract:

In classic galactosemia (CG) patients, aldose reductase (AR) converts galactose to galactitol. In a phase 1/2, placebo‐controlled study (NCT04117711), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of govorestat were evaluated after single and multiple ascending doses (0.5‐40 mg/kg) in healthy adults (n = 81) and CG patients (n = 14). Levels of govorestat in plasma and cerebrospinal fluid (CSF) and blood levels of galactitol, galactose, and galactose‐1‐phosphate (Gal‐1p) were measured for population PK and PK/PD analyses. Govorestat was well tolerated. Adverse event frequency was comparable between placebo and govorestat. Govorestat PK displayed a 2‐compartment model with sequential zero‐ and first‐order absorption, and no effect of demographic factors. Multiple‐dose PK of govorestat was linear in the 0.5‐40 mg/kg range, and CSF levels increased dose dependently. Elimination half‐life was ∼10 h. PK/PD modeling supported once‐daily dosing. Change from baseline in galactitol was −15% ± 9% with placebo and −19% ± 10%, −46% ± 4%, and −51% ± 5% with govorestat 5, 20, and 40 mg/kg, respectively, thus was similar for 20 and 40 mg/kg. Govorestat did not affect galactose or Gal‐1p levels. In conclusion, govorestat displayed a favorable safety, PK, and PD profile in humans, and reduced galactitol levels in the same magnitude (∼50%) as in a rat model of CG that demonstrated an efficacy benefit on neurological, behavioral, and ocular outcomes.

2023-05-22·JCI insight

Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency.

Article

作者: Shy, Michael ; Perfetti, Riccardo ; Saporta, Mario ; Canic, Tijana ; Rebelo, Adriana P ; Shendelman, Shoshana ; Tao, Xianzun ; Zhu, Yi ; Lobato, Amanda G ; Züchner, Stephan ; Zhai, R Grace ; Yanick, Christopher ; Syed, Sheyum ; Ortiz-Vega, Natalie

Sorbitol dehydrogenase (SORD) deficiency has been identified as the most frequent autosomal recessive form of hereditary neuropathy. Loss of SORD causes high sorbitol levels in tissues due to the inability to convert sorbitol to fructose in the 2-step polyol pathway, leading to degenerative neuropathy. The underlying mechanisms of sorbitol-induced degeneration have not been fully elucidated, and no current FDA-approved therapeutic options are available to reduce sorbitol levels in the nervous system. Here, in a Drosophila model of SORD deficiency, we showed synaptic degeneration in the brain, neurotransmission defect, locomotor impairment, and structural abnormalities in the neuromuscular junctions. In addition, we found reduced ATP production in the brain and ROS accumulation in the CNS and muscle, indicating mitochondrial dysfunction. Applied Therapeutics has developed a CNS-penetrant next-generation aldose reductase inhibitor (ARI), AT-007 (govorestat), which inhibits the conversion of glucose to sorbitol. AT-007 significantly reduced sorbitol levels in patient-derived fibroblasts, induced pluripotent stem cell-derived (iPSC-derived) motor neurons, and Drosophila brains. AT-007 feeding in Sord-deficient Drosophila mitigated synaptic degeneration and significantly improved synaptic transduction, locomotor activity, and mitochondrial function. Moreover, AT-007 treatment significantly reduced ROS accumulation in Drosophila CNS, muscle, and patient-derived fibroblasts. These findings uncover the molecular and cellular pathophysiology of SORD neuropathy and provide a potential treatment strategy for patients with SORD deficiency.

2017-01-01·Journal of pathogens

A Laboratory Assessment of Two Local Strains of the Beauveria bassiana (Bals.) Vuill. against the Tetranychus urticae (Acari: Tetranychidae) and Their Potential as a Mycopesticide

Article

作者: Algur, Omer Faruk ; Ortucu, Serkan

This study was conducted to assess highly pathogenic Beauveria bassiana isolates to be used in biocontrol and to determine their potentials as mycopesticide. For this purpose, two B. bassiana isolates, which were locally isolated from T. urticae, were chosen. Firstly, three suspensions were investigated at the degree of humidity of 65 ± 5% and 100% RH. Secondly, these strains were selected according to their tendency to mass production, tolerance to UV radiation, and capability of producing spore at the different temperatures. Finally, identification of the selected isolate was performed by using ITS rDNA analysis. Both tested fungal isolates were pathogenic to the T. urticae. Mycelial growths of isolate AT076 at 20°C and 30°C were found to be greater than isolate AT007. It was observed that isolate AT076 had more spore production with 1.61 × 107 spore/disc at 30°C and 44.33% germination after UV radiation for 15 min. The numbers of spores per 5 mm disk area for isolates AT076 and AT007 were found to be 1.2 × 106 and 1.0 × 106. These results show that isolate AT076 was more virulent and more UV-tolerant and had higher tendency to mass production compared to isolate AT007 against T. urticae. As a result of this study, isolate AT076 can be used in the biocontrol as mycopesticide.

116

项与 Govorestat 相关的新闻（医药）

2025-02-07

·PRNewswire

Applied Therapeutics, Inc. Sued for Securities Law Violations - Investors Should Contact Levi & Korsinsky Before February 18, 2025 to Discuss Your Rights - APLT

NEW YORK, Feb. 7, 2025 /PRNewswire/ -- Levi & Korsinsky, LLP notifies investors in Applied Therapeutics, Inc. ("Applied Therapeutics" or the "Company") (NASDAQ: APLT) of a class action securities lawsuit. CLASS DEFINITION: The lawsuit seeks to recover losses on behalf of Applied Therapeutics investors who were adversely affected by alleged securities fraud between January 3, 2024 and December 2, 2024. Follow the link below to get more information and be contacted by a member of our team: APLT investors may also contact Joseph E. Levi, Esq. via email at [email protected] or by telephone at (212) 363-7500. CASE DETAILS: According to the complaint, on November 27, 2024, Applied Therapeutics issued a press release announcing that it had received a Complete Response Letter (CRL) for the New Drug Application (NDA) for govorestat, the Company's lead drug candidate. The CRL indicated that the FDA completed its review of the application and determined that it was unable to approve the NDA in its current form citing deficiencies in the clinical application. Following this news, the price of Applied Therapeutics' common stock declined dramatically. From a closing market price of $10.21 per share on November 26, 2024, Applied Therapeutics' stock price fell to $8.57 per share on November 27, 2024 before falling further to $2.03 on November 29, 2024 and $1.75 per share on December 2, 2024, a total decline of more than 80%. After market hours on December 2, 2024, Applied Therapeutics disclosed it received a "warning letter" from the FDA referring to the clinical trial issues underlying the CRL. Applied Therapeutics' disclosure of the "warning letter" prompted a further decline in the stock price as investors discovered the seriousness and severity of the Company's clinical trial errors. From a closing market price of $1.75 per share on December 2, 2024, Applied Therapeutics' stock price fell to $1.69 per share on December 3, 2024 before falling further to $1.38 per share on December 4, 2024 and $1.29 per share on December 5, 2024. WHAT'S NEXT? If you suffered a loss in Applied Therapeutics during the relevant time frame, you have until February 18, 2025 to request that the Court appoint you as lead plaintiff. Your ability to share in any recovery doesn't require that you serve as a lead plaintiff. NO COST TO YOU: If you are a class member, you may be entitled to compensation without payment of any out-of-pocket costs or fees. There is no cost or obligation to participate. WHY LEVI & KORSINSKY: Over the past 20 years, the team at Levi & Korsinsky has secured hundreds of millions of dollars for aggrieved shareholders and built a track record of winning high-stakes cases. Our firm has extensive expertise representing investors in complex securities litigation and a team of over 70 employees to serve our clients. For seven years in a row, Levi & Korsinsky has ranked in ISS Securities Class Action Services' Top 50 Report as one of the top securities litigation firms in the United States. CONTACT: Levi & Korsinsky, LLP Joseph E. Levi, Esq. Ed Korsinsky, Esq. 33 Whitehall Street, 17th Floor New York, NY 10004 [email protected] Tel: (212) 363-7500 Fax: (212) 363-7171 SOURCE Levi & Korsinsky, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

申请上市

2025-01-31

·PRNewswire

Shareholders that lost money on Applied Therapeutics, Inc.(APLT) Urged to Join Class Action - Contact Levi & Korsinsky to Learn More

NEW YORK, Jan. 31, 2025 /PRNewswire/ -- Levi & Korsinsky, LLP notifies investors in Applied Therapeutics, Inc. ("Applied Therapeutics" or the "Company") (NASDAQ: APLT) of a class action securities lawsuit. CLASS DEFINITION: The lawsuit seeks to recover losses on behalf of Applied Therapeutics investors who were adversely affected by alleged securities fraud between January 3, 2024 and December 2, 2024. Follow the link below to get more information and be contacted by a member of our team: APLT investors may also contact Joseph E. Levi, Esq. via email at [email protected] or by telephone at (212) 363-7500. CASE DETAILS: According to the complaint, on November 27, 2024, Applied Therapeutics issued a press release announcing that it had received a Complete Response Letter (CRL) for the New Drug Application (NDA) for govorestat, the Company's lead drug candidate. The CRL indicated that the FDA completed its review of the application and determined that it was unable to approve the NDA in its current form citing deficiencies in the clinical application. Following this news, the price of Applied Therapeutics' common stock declined dramatically. From a closing market price of $10.21 per share on November 26, 2024, Applied Therapeutics' stock price fell to $8.57 per share on November 27, 2024 before falling further to $2.03 on November 29, 2024 and $1.75 per share on December 2, 2024, a total decline of more than 80%. After market hours on December 2, 2024, Applied Therapeutics disclosed it received a "warning letter" from the FDA referring to the clinical trial issues underlying the CRL. Applied Therapeutics' disclosure of the "warning letter" prompted a further decline in the stock price as investors discovered the seriousness and severity of the Company's clinical trial errors. From a closing market price of $1.75 per share on December 2, 2024, Applied Therapeutics' stock price fell to $1.69 per share on December 3, 2024 before falling further to $1.38 per share on December 4, 2024 and $1.29 per share on December 5, 2024. WHAT'S NEXT? If you suffered a loss in Applied Therapeutics during the relevant time frame, you have until February 18, 2025 to request that the Court appoint you as lead plaintiff. Your ability to share in any recovery doesn't require that you serve as a lead plaintiff. NO COST TO YOU: If you are a class member, you may be entitled to compensation without payment of any out-of-pocket costs or fees. There is no cost or obligation to participate. WHY LEVI & KORSINSKY: Over the past 20 years, the team at Levi & Korsinsky has secured hundreds of millions of dollars for aggrieved shareholders and built a track record of winning high-stakes cases. Our firm has extensive expertise representing investors in complex securities litigation and a team of over 70 employees to serve our clients. For seven years in a row, Levi & Korsinsky has ranked in ISS Securities Class Action Services' Top 50 Report as one of the top securities litigation firms in the United States. CONTACT: Levi & Korsinsky, LLP Joseph E. Levi, Esq. Ed Korsinsky, Esq. 33 Whitehall Street, 17th Floor New York, NY 10004 [email protected] Tel: (212) 363-7500 Fax: (212) 363-7171 SOURCE Levi & Korsinsky, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

申请上市

2025-01-30

·PRNewswire

The Gross Law Firm Reminds Applied Therapeutics Investors of the Pending Class Action Lawsuit with a Lead Plaintiff Deadline of February 18, 2025 - APLT

NEW YORK, Jan. 30, 2025 /PRNewswire/ -- The Gross Law Firm issues the following notice to shareholders of Applied Therapeutics, Inc. (NASDAQ: APLT). Shareholders who purchased shares of APLT during the class period listed are encouraged to contact the firm regarding possible lead plaintiff appointment. Appointment as lead plaintiff is not required to partake in any recovery. CONTACT US HERE: CLASS PERIOD: January 3, 2024 to December 2, 2024 ALLEGATIONS: According to the complaint, on November 27, 2024, Applied Therapeutics issued a press release announcing that it had received a Complete Response Letter (CRL) for the New Drug Application (NDA) for govorestat, the Company's lead drug candidate. The CRL indicated that the FDA completed its review of the application and determined that it was unable to approve the NDA in its current form citing deficiencies in the clinical application. Following this news, the price of Applied Therapeutics' common stock declined dramatically. From a closing market price of $10.21 per share on November 26, 2024, Applied Therapeutics' stock price fell to $8.57 per share on November 27, 2024 before falling further to $2.03 on November 29, 2024 and $1.75 per share on December 2, 2024, a total decline of more than 80%. After market hours on December 2, 2024, Applied Therapeutics disclosed it received a "warning letter" from the FDA referring to the clinical trial issues underlying the CRL. Applied Therapeutics' disclosure of the "warning letter" prompted a further decline in the stock price as investors discovered the seriousness and severity of the Company's clinical trial errors. From a closing market price of $1.75 per share on December 2, 2024, Applied Therapeutics' stock price fell to $1.69 per share on December 3, 2024 before falling further to $1.38 per share on December 4, 2024 and $1.29 per share on December 5, 2024. DEADLINE: February 18, 2025 Shareholders should not delay in registering for this class action. Register your information here: NEXT STEPS FOR SHAREHOLDERS: Once you register as a shareholder who purchased shares of APLT during the timeframe listed above, you will be enrolled in a portfolio monitoring software to provide you with status updates throughout the lifecycle of the case. The deadline to seek to be a lead plaintiff is February 18, 2025. There is no cost or obligation to you to participate in this case. WHY GROSS LAW FIRM? The Gross Law Firm is a nationally recognized class action law firm, and our mission is to protect the rights of all investors who have suffered as a result of deceit, fraud, and illegal business practices. The Gross Law Firm is committed to ensuring that companies adhere to responsible business practices and engage in good corporate citizenship. The firm seeks recovery on behalf of investors who incurred losses when false and/or misleading statements or the omission of material information by a company lead to artificial inflation of the company's stock. Attorney advertising. Prior results do not guarantee similar outcomes. CONTACT: The Gross Law Firm 15 West 38th Street, 12th floor New York, NY, 10018 Email: [email protected] Phone: (646) 453-8903 SOURCE The Gross Law Firm WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

申请上市

100 项与 Govorestat 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
半乳糖血症	申请上市	欧盟	Applied Therapeutics, Inc.	2023-12-01
山梨糖醇脱氢酶缺乏症	临床3期	美国	Applied Therapeutics, Inc.	2022-01-01
山梨糖醇脱氢酶缺乏症	临床3期	捷克	Applied Therapeutics, Inc.	2022-01-01
山梨糖醇脱氢酶缺乏症	临床3期	意大利	Applied Therapeutics, Inc.	2022-01-01
山梨糖醇脱氢酶缺乏症	临床3期	英国	Applied Therapeutics, Inc.	2022-01-01
1A型先天性糖基化障碍	临床1期	-	Applied Therapeutics, Inc.	-

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临床结果

适应症

分期

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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


NCT05397665 (INSPIRE, Biospace) 人工标引	临床2/3期	山梨糖醇脱氢酶缺乏症	56	Govorestat	選憲襯獵積範夢醖簾繭(繭糧繭鏇範鏇遞憲鏇鑰) = Demonstrated statistically significant correlation between sorbitol level and the prespecified CMT-FOM composite clinical endpoint (10-meter walk-run test, 4 stair climb, sit to stand test,6-minute walk test and dorsiflexion) (p=0.05). 餘簾窪鹽積齋鹹鹽鑰繭 (淵繭襯鑰糧築觸餘繭夢 ) 达到更多	积极	2024-02-15
				Placebo
Corporate Publications 人工标引	临床3期	半乳糖血症	-	AT-007	鏇艱壓糧鹹壓憲網膚鹹(範窪衊醖壓觸遞醖餘範) = Review of the data at 12 months of treatment by the DMC indicated that while the study primary endpoint has not yet reached statistical significance, a trend exists favoring AT-007 vs. placebo. 膚構艱築築觸餘廠蓋願 (選膚範獵構餘餘網淵觸 )	积极	2022-10-06
				Placebo