Phase III, Placebo-controlled, Randomized, Double-blind, Multicenter, Parallel-group comparative study to Evaluate the Efficacy and Safety of Patient Initiated Therapy of ASP2151 in Patients with Recurrent Herpes Labialis

开始日期2019-09-25

申办/合作机构

Maruho Co., Ltd.

JPRN-JapicCTI-194954 / Completed临床3期

开始日期2019-09-25

申办/合作机构

Maruho Co., Ltd.

100 项与阿莫奈韦相关的临床结果

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100 项与阿莫奈韦相关的转化医学

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100 项与阿莫奈韦相关的专利（医药）

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项与阿莫奈韦相关的文献（医药）

2025-01-01·CORNEA

Efficacy and Safety of Amenamevir, a Helicase-Primase Inhibitor for the Treatment of Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis

Article

作者: Barreau, Emmanuel ; Haigh, Oscar ; Rousseau, Antoine ; Fernandez, José ; Vauloup-Fellous, Christelle ; Labetoulle, Marc ; Boucher, Rafael ; Boutolleau, David ; Burrel, Sonia

Purpose::

The purpose of this study was to describe the efficacy and tolerance of amenamevir (AMNV), an inhibitor of the viral helicase-primase, for the treatment of recalcitrant herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) herpes simplex virus 1 strains.

Methods::

In this retrospective case series, 6 consecutive patients with HSK caused by an ACVR herpes simplex virus 1 strain with a failure of conventional antiviral therapy were included after having been treated with AMNV (there was no control group of comparable patients for whom previous treatment would have been continued despite its inefficacy). Medical files were assessed for clinical data including reason(s) for AMNV introduction (frequent recurrences despite appropriate preventive antiviral treatment and/or clinical resistance to suppressive antiviral treatment of an ongoing clinical relapse), genotypical resistance to herpes simplex virus 1 documentation, immune status, clinical types and number of HSK episodes before and during AMNV treatment, adverse effects observed during AMNV treatment, and best corrected visual acuity.

Results::

Of 6 patients, 4 (66%) did not experience a single recurrence during AMNV therapy while 2 others had recurrences (1 over 24 months of treatment and 2 over 23 months, ie two-fold less frequently than with conventional preventive treatment). On the overall history of these 6 patients, AMNV appeared to be associated with a reduction in HSK recurrences, with a mean of only 0.02 ± 0.04 episodes/month during follow-up under AMNV as compared to 0.14 ± 0.04 episodes/month in the year preceding AMNV introduction (P = 0.03). Improvement in vision acuity was also observed (mean best corrected visual acuity 0.17 ± 0.12 logarithm of the minimum angle of resolution at the end of follow-up vs. 0.30 ± 0.35 before AMNV onset), albeit nonsignificant probably due to the limited number of patients (P = 0.38). Neither clinical nor biological adverse effects were observed while under AMNV during the follow-up (16.5 ± 5.8 months).

Conclusions::

Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences.

2024-11-01·JOURNAL OF MEDICAL VIROLOGY

Single Amino Acid Substitution Within the Helicase of Varicella Zoster Virus Makes It Resistant to Amenamevir

Article

作者: Ishimaru, Hanako ; Nishimura, Mitsuhiro ; Aoki, Kaito ; Mori, Yasuko ; Effendi, Gema Barlian ; Takamiya, Rei ; Marini, Maria Istiqomah

ABSTRACT:

A helicase‐primase inhibitor, amenamevir (ASP2151), is the active pharmaceutical ingredient of a drug for the herpes zoster that is caused by reactivation of varicella‐zoster virus (VZV). Here we report a new amenamevir‐resistant VZV isolated under the selection pressure of amenamevir. The resistant virus has a nonsynonymous mutation K350N in the helicase gene ORF55. A recombinant virus artificially constructed harboring the ORF55 K350N also acquired amenamevir resistance, and thus the single amino‐acid substitution in helicase is revealed to be responsible for the resistance. We observed that the drug‐resistant virus and the ORF55 K350N recombinant virus have high resistance to amenamevir, as the EC50 values in a plaque reduction assay were > 100 μM, while the two viruses remained susceptible to the nucleoside analog drug acyclovir. No defect in viral growth was observed for these resistant viruses in a plaque size assay in human malignant melanoma cells. However, defect in plaque formation was observed from resistant virus in human fetal lung fibroblast cells, showing that the growth of the resistant virus is dependent on the cell type. We observed that the single amino‐acid substitution in the helicase induces amenamevir resistance, confirming the importance of the helicase in amenamevir's inhibition of virus growth. Our findings highlight the importance of regulating the clinical use of amenamevir to minimize the risk of the emergence of helicase K350N mutation, especially in the long‐term use of amenamevir by immunosuppressed patients.

2024-10-02·EXPERT OPINION ON THERAPEUTIC PATENTS

Helicase–primase inhibitors for the treatment of herpes simplex virus infections – patent evaluation of WO2023/225162 from Gilead Sciences Inc

Review

作者: Kleymann, Gerald ; Gege, Christian

Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors (HPIs). Here, we analyze the first patent application from Gilead in this field, which pursued a me-too approach combining elements from an old Bayer together with a recent Medshine HPI application (which covers the Phaeno Therapeutics drug candidate HN0037). The asset was contributed to Assembly Biosciences, where it is under development as ABI-1179 at the investigational new drug (IND) enabling stage for high-recurrence genital herpes. A structure proposal for indolinoyl derivative ABI-1179 is presented, showing its potential opportunities and limitations compared to other HPIs.

项与阿莫奈韦相关的新闻（医药）

2024-06-05

·maruho.co.jp

Maruho and Hyphens Pharma Announce Exclusive License Agreement for Anti-herpes Virus Agent (INN: Amenamevir) in 10 ASEAN Countries

Osaka (Japan), June 5, 2024 - Maruho Co., Ltd. ("Maruho", Head Office: Osaka, Japan, President and CEO: Atsushi Sugita) and Hyphens Pharma Pte. Ltd., a subsidiary of Hyphens Pharma International Limited ("Hyphens", Head Office: Singapore, Chairman, Executive Director and CEO: Lim See Wah) announced that the two companies have entered into a license agreement under which Maruho will license to Hyphens the rights to develop and commercialize the anti-herpes virus agent amenamevir (JNN/INN), manufactured and marketed in Japan by Maruho, hereinafter referred to as "the product", in 10 ASEAN (Association of Southeast Asian Nations)*1 countries. Under the terms of the agreement, Maruho grants Hyphens an exclusive license to develop and market the product in 10 ASEAN countries. Hyphens will proceed with the development activities necessary to bring the product to market. After the product is commercialized, Hyphens will pay royalties to Maruho based on commercialization milestones. The product exhibits high antiviral activity against the varicella-zoster virus and the herpes simplex virus by inhibiting the activity of the helicase-primase complex, which is essential for viral DNA replication. In 2012, Maruho and Astellas Pharma Inc. executed a license agreement for the development and commercialization of the product. Maruho proceeded with development in Japan and the product was approved for the indications of "herpes zoster" in 2017 and "recurrent herpes simplex" in 2023. The product is currently manufactured and commercialized under the brand name of "Amenalief® Tablets 200 mg" in Japan. In its 5th Medium-Term Plan, initiated in October 2023, Maruho introduced a new business strategy termed the "Asia Dermatology Hub Concept." Maruho established a local subsidiary in China*2 in February 2024 and is promoting business development in Asian countries and regions. This agreement is an effort to realize business development in Asia and to respond to the unmet needs of patients in ASEAN countries who have limited options for herpes treatment. Maruho and Hyphens, which both specialize in dermatology, will work to bring smiles to the faces of patients suffering from viral skin diseases such as herpes zoster and herpes simplex in the countries and regions covered by this agreement. Note The information contained in this news release in regard to pharmaceutical and developmental products is not intended for the purpose of promotion, advertising or medical advice. (*1) Thailand, Indonesia, Malaysia, Philippines, Singapore, Vietnam, Brunei, Cambodia, Myanmar, Laos (*2) Establishment of a local subsidiary in China (February 2024) https://www.maruho.co.jp/english/information/20240222.html [References] Maruho Launches Anti-Herpes Virus Agent "Amenalief Tab. 200mg" in Japan (2017/09/02) https://www.maruho.co.jp/english/information/2017090702.html Maruho Receives Manufacturing and Marketing Approval for a Partial Change of the Indication and Dosage/Administration for Anti-herpes Virus Agent "Amenalief Tab. 200mg" for the Treatment of Recurrent Herpes Simplex in Japan (2023/02/24) https://www.maruho.co.jp/english/information/20230224.html About HyphensHyphens Pharma International Limited and its subsidiaries (the "Group") is Singapore's leading specialty pharmaceutical and consumer healthcare group, leveraging on its diverse footprint in ASEAN countries. The Group has a direct presence in Singapore, Vietnam, Malaysia, Indonesia, and the Philippines, and is supplemented by a marketing and distribution network covering 14 other markets. The Group's core business comprises Specialty Pharma Principals, Proprietary Brands, and Medical Hypermart & Digital. Besides marketing and selling a range of specialty pharmaceutical products in selected ASEAN countries through exclusive distributorship or licensing and supply agreements with brand principals mainly from Europe and the United States, the Group also develops, markets, and sells its own proprietary range of dermatological and health supplement products. For more information, please visit https://www.hyphensgroup.com/ About MaruhoMaruho Co., Ltd. has its head office in Osaka and leads Japan in research and development, manufacturing and commercialization of dermatological products. Founded in 1915, Maruho has 1,566 employees (as of the end of September 2023), and net sales were approximately 85.71 billion yen in its fiscal year ended September 30, 2023. With the mission "More smiles, brighter life for you.", Maruho aims to help realize a society where everyone can live with a smile. For more information, please visit www.maruho.co.jp/english/ Contact Information: Maruho Co., Ltd. Public Relations Group, Corporate Planning Dept. Tel：+81-(0)6-6371-8831 Fax：+81-(0)6-6371-8679 Email：kouhou@mii.maruho.co.jp

引进/卖出上市批准

2023-02-24

·maruho.co.jp

Maruho Receives Manufacturing and Marketing Approval for a Partial Change of the Indication and Dosage/Administration for Anti-herpes Virus Agent "Amenalief Tab. 200mg" for the Treatment of Recurrent Herpes Simplex in Japan

Osaka (Japan), February 24, 2023 - Maruho Co., Ltd. ("Maruho", Head Office: Osaka, Japan,President and CEO: Atsushi Sugita) announces that it has received manufacturing and marketing approval from the Ministry of Health, Labor and Welfare for a partial change of the indication and dosage/administration for anti-herpes virus agent "Amenalief® Tab. 200mg" (JAN/INN: amenamevir; hereinafter referred to as "the product") for the treatment of recurrent herpes simplex in Japan. Herpes simplex is a general term for infectious diseases caused by the herpes simplex virus that infects the skin and mucous membranes (lips, eyes, genitals, etc.). Common types include labial herpes and genital herpes. Recurrent herpes simplex is a disease that develops when the herpes simplex virus that has been latently infected in the ganglia after a primary infection, is reactivated by stimuli such as stress or a weakened immune system. Additionally, it is characterized by repeated recurrence of symptoms, and many patients experience discomfort such as itching and tingling before skin symptoms such as erythema (redness), papules and blisters develop. The partial change of the indication and dosage/administration approval received today is recognized as "Patient Initiated Treatment" (PIT) for patients with recurrent herpes simplex when they become aware of the initial symptoms.1) Early treatment is possible by taking the prescribed 1200mg of this drug once after meals within 6 hours after the appearance of the initial symptoms of recurrent herpes simplex. It is hoped that this drug will be more convenient for patients since only one dose is required. Maruho, specializing in dermatology, will strive to further contribute to patients and medical professionals by providing new options for the treatment of recurrent herpes simplex. Note The information contained in this news release in regard to pharmaceutical and developmental products is not intended for the purpose of promotion, advertising or medical advice. Product Profile Brand Name Amenalief® Tab. 200mg JAN/INN Amenamevir Formulation/Dose Film coated tablets containing 200mg of amenamevir in 1 tablet Indication (Additional content is underlined) Herpes Zoster Recurrent Herpes Simplex Dosage and Administration (Additional content is underlined) (Herpes Zoster) General administration for adults is 400mg of amenamevir once a day administered orally after a meal. (Recurrent Herpes Simplex) General administration for adults is 1200mg of amenamevir administered orally after a meal. References １） Shinichiro Yasumoto, Patient-initiated-treatment (PIT) in the management of patients with recurrent herpes simplex, Japanese Journal of Clinical Dermatology, 74 (5), 135 (2020) About Amenalief Tab.Amenalief Tab. is an oral anti-herpes virus agent with a novel mechanism of action containing the non-nucleic acid analog amenamevir, created in Japan by Astellas Pharma Inc. By inhibiting the activity of the helicase-primase complex, an essential enzyme for DNA replication of the herpesvirus, it exhibits antiviral activity by suppressing double-stranded DNA cleavage and RNA primer synthesis. Maruho manufactures and commercializes the product in Japan and it has been used for the treatment of herpes zoster since 2017. Maruho's initiatives for disease caused by herpesMaruho is working to help patients suffering from herpes labialis and genital herpes to understand the diseases correctly and take appropriate measures in the event of a recurrence. Through the comprehensive herpes information site "What's herpes?" the causes and remedies for cold sores and genital herpes are explained. (https://www.maruho.co.jp/kanja/herpes/） (As Maruho markets treatments for customers in Japan, the information is only provided in Japanese). About MaruhoMaruho Co., Ltd. has its head office in Osaka and leads Japan in research and development, manufacturing and commercialization of dermatological products. Founded in 1915, Maruho has 1,547 employees (as of the end of September 2022), and net sales were approximately 85.67 billion yen in its fiscal year ended September 30, 2022. Pursuing its long-term corporate vision of "Excellence in Dermatology," Maruho is striving to improve the health and quality of life of people all over the world. For more information, please visit https://www.maruho.co.jp/english/ Contact Information: Maruho Co., Ltd. Corporate Communications Dept. Tel：+81-(0)6-6371-8831 Fax：+81-(0)6-6371-8679 e-mail：kouhou@mii.maruho.co.jp

上市批准临床研究

2021-01-21

·BioSpace

Chemo Drug Potentially More Potent than Remdesivir Against Coronavirus

Researchers with Shenzhen Institutes of Advanced Technology in China used a variety of computational techniques to simulate drug-virus interactions. They then screened 1,906 existing drugs to evaluate which ones might inhibit replication of SARS-CoV-2, the virus that causes COVID-19. From this broad screening, they identified four drugs that had potential to prevent replication of the virus, which they then tested in laboratory experiments. Two of the drugs, pralatrexate, a chemotherapy, and azithromycin, an antibiotic, were successful at preventing replication of the virus. More lab experiments demonstrated that pralatrexate had stronger viral inhibition than Gilead Sciences’ remdesivir, which is currently the only approved drug for COVID-19. They published their research in the journal PLOS Computational Biology. Pralatrexate is marketed by Acrotech Biopharma under the trade name Folotyn. It is indicated for relapsed or refractory peripheral T-cell lymphoma. Like many chemotherapeutics, it comes with a wide range of serious side effects, including low blood cell counts—platelets, white blood cells, and red blood cells—mucositis, which is inflamed mucous membranes, severe skin reactions, tumor lysis syndrome (TLS), increased risk of serious reactions in kidney patients, fever, dehydration, nausea, as well as significant risk for pregnant and nursing women. As a result, the authors note that immediate use of the drug for COVID-19 patients is not guaranteed, but believe their approach was useful in identifying drugs that can be repurposed. “We have demonstrated the value of our novel hybrid approach that combines deep-learning technologies with more traditional simulations of molecular dynamics,” said Haiping Zhang, study author. The research team is working to develop more computational methods for creating novel molecular structures that could be developed into new drugs to treat COVID-19. The screening method focused on viral RNA-dependent RNA polymerase (RdRp), a promising therapeutic target. The authors write that other computational drug screening methods are based on molecular docking, deep learning or Molecular Dynamics. Most of these typically depend upon a single technique or lack experimental validation. “Each computation method,” they write, “with its underlying philosophy, often has its own strong and weak points, while a proper combination and modification of such methods could provide a better solution. Previously, we have developed two deep learning-based models to estimate protein-ligand interactions: DFCNN and DeepBindBC. DFCNN uses molecular vector data of protein pocket and ligand, instead of spatial information at interaction site, to estimate the protein-ligand pair as binding or non-binding with a probability value between 0 and 1. DeepBindBc estimates the binding possibility from atom contact information at interaction surface of a modelled 3D protein-ligand complex. The input of DeepBindBC contains spatial information of the protein-ligand interface, thus it strongly complements DFCNN.” Their hybrid screening procedure was made up of DFCNN, DeepBindBC, Autodoc Vina, pocket localized molecular dynamics simulation, metadynamics, and their own inhouse-developed tools. They screened potential drugs from the TargetMol-Approved_Drug_Library, which contains 1,906 currently marketed drugs. One of the findings, less focused on COVID-19, but of particular interest to validation of the screening approach, was that DFCNN, DeepBindBC and Autodock Vina predicted different drug compounds as top hits. For example, amenamevir and azithromycin had better scores on Autodock Vina, while odanacatib and nitisinone had higher DFCNN scores. Azithromycin, with hydroxychloroquine, an anti-malarial, had demonstrated efficacy in treating COVID-19 earlier in the pandemic, but subsequent studies have failed to show that either drug is effective in treating COVID-19. For that matter, a large World Health Organization (WHO) study failed to prove remdesivir’s effectiveness in hospitalized patients, resulting in the organization issuing a conditional recommendation against its use.

100 项与阿莫奈韦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10564	阿莫奈韦	J05AX26	DB11701

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
单纯疱疹	日本	Maruho Co., Ltd.	2023-02-24
带状疱疹	日本	Maruho Co., Ltd.	2017-07-03

未上市

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
生殖器疱疹	临床2期	美国	Astellas Pharma, Inc.	2007-06-21

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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


NCT01959295 (CTgov)	临床3期	单纯疱疹	468	ASP2151 (ASP2151)	膚築膚簾獵壓廠網淵鏇(顧顧築網範鑰積遞簾網) = 鬱膚蓋網觸網膚製顧餘鹹齋艱糧淵簾願網膚範 (鑰衊獵餘壓膚鑰窪簾範, 齋鬱憲願積繭膚鹽鹹鹹 ~ 願餘遞艱鑰齋衊襯膚積) 更多	-	2024-10-09
				ASP2151 placebo (ASP2151 Placebo)	膚築膚簾獵壓廠網淵鏇(顧顧築網範鑰積遞簾網) = 簾鹹構網鹽鹽鹽觸壓鏇鹹齋艱糧淵簾願網膚範 (鑰衊獵餘壓膚鑰窪簾範, 膚淵鏇構構選築壓夢窪 ~ 夢鏇鏇衊鏇構觸簾獵積) 更多
NCT02209324 (CTgov)	临床3期	单纯疱疹	275	ASP2151	廠網艱壓網衊蓋範夢築(簾繭網繭構範鬱淵網鏇) = 膚範鬱繭鹽憲網壓廠壓壓範獵鏇製築鏇鹽選淵 (築壓構簾鹹壓壓憲鏇顧, 齋衊艱鹽淵繭廠艱鏇鑰 ~ 齋鬱築簾壓繭鹽製願鏇) 更多	-	2024-09-27
NCT02321748 (CTgov)	临床1期	-	24	Montelukast+ASP2151 (Montelukast)	積夢繭顧膚範蓋鏇積製(餘選鏇網壓壓淵構夢範) = 顧選壓獵網選艱壓鏇構獵網顧齋獵獵構糧襯鑰 (鬱積顧鑰築願壓鹹選築, 窪淵遞鹹壓夢窪鹹繭願 ~ 衊壓選窪繭積窪艱製醖) 更多	-	2019-01-14
				Montelukast+ASP2151 (ASP2151)	積夢繭顧膚範蓋鏇積製(餘選鏇網壓壓淵構夢範) = 衊膚網鹽餘衊憲糧襯鏇獵網顧齋獵獵構糧襯鑰 (鬱積顧鑰築願壓鹹選築, 願繭願觸遞膚廠鏇願範 ~ 觸築齋餘顧鹽鬱憲鬱襯) 更多
NCT01959841 (CTgov)	临床3期	带状疱疹	751	ASP2151 (ASP2151(200 mg))	膚憲淵鏇夢廠鬱積觸積(窪範繭繭鹹構膚鹹網夢) = 鹽齋簾構鹽廠築網觸壓膚糧獵選積衊憲膚獵衊 (鏇簾構獵齋遞鏇餘鬱鏇, 窪淵廠餘淵遞願鏇膚觸 ~ 構網齋鬱鹽衊襯衊鏇襯) 更多	-	2018-10-18
				ASP2151 (ASP2151(400mg))	膚憲淵鏇夢廠鬱積觸積(窪範繭繭鹹構膚鹹網夢) = 鑰糧醖觸遞醖齋膚膚衊膚糧獵選積衊憲膚獵衊 (鏇簾構獵齋遞鏇餘鬱鏇, 繭襯鏇鹽鹽膚範壓鏇餘 ~ 夢廠窪憲構築夢觸襯鹹) 更多
NCT00486200 (Pubmed \| J Infect Dis)	临床2期	生殖器疱疹	695	ASP2151 100 mg	糧顧選廠鹹製製廠餘簾(餘鑰膚齋齋蓋艱繭廠襯) = 願餘壓鬱淵淵範繭鑰艱齋艱廠襯襯願構糧簾鹹 (壓膚齋網醖淵膚鏇簾顧 )	-	2012-04-01
				ASP2151 200 mg	糧顧選廠鹹製製廠餘簾(餘鑰膚齋齋蓋艱繭廠襯) = 鹽蓋膚遞製餘壓觸蓋鬱齋艱廠襯襯願構糧簾鹹 (壓膚齋網醖淵膚鏇簾顧 )