The purpose of this study is to evaluate the long-term safety and efficacy of donidalorsen in people with HAE and the effects of donidalorsen on the number of HAE attacks and their impact on quality of life (QoL).

开始日期2022-07-13

申办/合作机构

Ionis Pharmaceuticals, Inc.

NCT05139810 / Completed临床3期

A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients With Hereditary Angioedema (HAE)

The purpose of this study is to evaluate the safety and efficacy of donidalorsen in participants with HAE and effect of donidalorsen on the quality and pattern of HAE attacks and their impact on quality of life (QoL).

开始日期2021-12-03

申办/合作机构

Ionis Pharmaceuticals, Inc.

NCT04549922 / Completed临床2期IIT

Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19: A Phase II Randomized Controlled Trial

Up to 1/3 of all patients infected with COVID-19 can develop complications that require hospitalization. Severe pneumonia associated with acute respiratory distress syndrome (ARDS) is the most threatening and feared complication of COVID-19 infection, with mortality rates close to 50% in some groups.
Autopsies between these severe cases reveal severe capillary involvement, with signs of intense inflammatory changes, microvascular thrombosis, endothelial injury and abnormal tissue repair. The available evidence suggests that abnormal activation or imbalance in the counter-regulation of the kallikrein-kinin system may play a central role in a positive feedback cycle, leading to consequent diffuse microangiopathy. Blockade of the kallikrein-kinin system can therefore prevent deterioration of lung function by reducing inflammation, edema and microthrombosis.
The objective of this phase IIb study is to assess the preliminary effects on the oxygenation parameters of an antisense oligonucleotide that inhibits pre-kallikrein synthesis in patients with moderate to severe COVID-19.

开始日期2020-10-19

申办/合作机构

Hospital do Coração

[+2]

100 项与 Donidalorsen 相关的临床结果

登录后查看更多信息

100 项与 Donidalorsen 相关的转化医学

登录后查看更多信息

100 项与 Donidalorsen 相关的专利（医药）

登录后查看更多信息

项与 Donidalorsen 相关的文献（医药）

2024-07-04·NEW ENGLAND JOURNAL OF MEDICINE

Efficacy and Safety of Donidalorsen for Hereditary Angioedema

Article

作者: Tachdjian, Raffi ; Wang, Sophie ; Manning, Michael E ; Treadwell, Sabrina ; Lumry, William R ; Reshef, Avner ; Craig, Timothy ; Newman, Kenneth B ; Yarlas, Aaron ; Stobiecki, Marcin ; Gelincik, Asli ; Bordone, Laura ; Riedl, Marc A ; Cohn, Danny M ; Jacobs, Joshua S ; Gokmen, Nihal M ; Karakaya, Gül ; Gompels, Mark M

BACKGROUND:

Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression.

METHODS:

In this phase 3, double-blind, randomized trial, we assigned patients with hereditary angioedema to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25.

RESULTS:

A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P = 0.004); the median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group. Donidalorsen administered every 4 weeks resulted in an improvement in the least-squares mean total score for the change at week 25 on the Angioedema Quality-of-Life Questionnaire (scores range from 0 to 100, with a score of 100 indicating the worst possible quality of life) that was 18.6 points (95% CI, 9.5 to 27.7) better than that with placebo (P<0.001). The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity.

CONCLUSIONS:

Donidalorsen treatment reduced the hereditary angioedema attack rate, a finding that supports potential prophylactic use for hereditary angioedema. (Funded by Ionis Pharmaceuticals; OASIS-HAE ClinicalTrials.gov number, NCT05139810.).

2024-04-01·The journal of allergy and clinical immunology. In practice

Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema

Article

作者: Riedl, Marc A ; Bordone, Laura ; Newman, Kenneth B ; Revenko, Alexey ; Cohn, Danny M

Hereditary angioedema (HAE) is typically caused by a deficiency of the protease inhibitor C1 inhibitor (C1INH). The absence of C1INH activity on plasma kallikrein and factor XIIa leads to overproduction of the vasoactive peptide bradykinin, with resulting angioedema. As the primary site of C1INH and prekallikrein production, the liver is recognized as an important therapeutic target in HAE, leading to the development of hepatic-focused treatment strategies such as GalNAc-conjugated antisense technology and gene modification. This report reviews currently available data on hepatic-focused interventions for HAE that have advanced into human trials. Donidalorsen is an investigational GalNAc₃-conjugated antisense oligonucleotide that binds to prekallikrein mRNA in the liver and reduces the expression of prekallikrein. Phase 2 data with subcutaneous donidalorsen demonstrated a significant reduction in HAE attack rate compared with placebo. Phase 3 trials are underway. ADX-324 is a GalNAc₃-conjugated short-interfering RNA being investigated in HAE. BMN 331 is an investigational AAV5-based gene therapy vector that expresses wild-type human C1INH and is targeted to hepatocytes. A single intravenous dose of BMN 331 is intended to replace the defective SERPING1 gene and enable patients to produce functional C1INH. A first-in-human phase 1/2 study is ongoing with BMN 331. NTLA-2002 is an investigational in vivo clustered regularly interspaced short palindromic repeats/Cas9-based therapy designed to knock out the prekallikrein-coding KLKB1 gene in hepatocytes; a phase 1/2 study is ongoing. Findings from these and other ongoing studies are highly anticipated with the expectation of expanding the array of treatment options in HAE.

2024-03-03·Expert opinion on investigational drugs

Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies

Review

作者: Farkas, Henriette ; Balla, Zsuzsanna

INTRODUCTION:

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema and predominantly caused by the dysregulation of the kinin-kallikrein system.

AREAS COVERED:

This manuscript presents the results of preclinical and early clinical trials of newer drugs targeting the dysregulated kinin-kallikrein system. ATN-249 is an oral drug that has shown promising results in preclinical and Phase I studies, and good tolerability in the prophylactic treatment of attacks. KVD900 is also an oral agent developed for the on-demand treatment of HAE attacks. It has shown positive results in Phase I/II studies, with rapid absorption. The third drug, IONIS-PKKRx, is an antisense oligonucleotide targeting plasma prekallikrein mRNA. It has shown a dose-dependent reduction of plasma prekallikrein levels and proenzyme activation in Phase I/II studies, and has shown promising results. STAR-0215 is a long acting anti-activated kallikrein monoclonal antibody. A Phase 1a single ascending dose trial evaluated its safety, pharmacokinetics, and pharmacodynamics. Lastly, NTLA-2002 is an investigational gene-editing therapy.

EXPERT OPINION:

The targeted treatment of the dysregulated kinin-kallikrein system with specific inhibitors is promising for the prevention of angioedema attacks. Ongoing phase III studies will provide further insight into the efficacy and long-term safety of these novel therapies, potentially expanding treatment options for HAE treatment.

项与 Donidalorsen 相关的新闻（医药）

2024-12-04

·GlobeNewswire-Health Care

Theratechnologies Announces Exclusive Licensing Agreement with Ionis to Commercialize Olezarsen and Donidalorsen in Canada

Addition of investigational RNA-targeted medicines build upon Theratechnologies’ foundational HIV portfolio Submissions to Health Canada planned for 2025 MONTREAL, Dec. 04, 2024 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (“Theratechnologies” or the “Company”) (TSX: TH) (NASDAQ: THTX), a pharmaceutical company focused on the development and commercialization of innovative therapies, today announced it has entered into an agreement with Ionis Pharmaceuticals, Inc. (Ionis) to license two investigational RNA-targeted medicines developed by Ionis. Under the agreement, Theratechnologies receives exclusive rights in Canada for olezarsen, which is being evaluated for familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG), and for donidalorsen, which is being evaluated for the treatment of hereditary angioedema (HAE). All figures are in U.S. dollars unless otherwise stated. “Theratechnologies is proud to be the partner of choice for Ionis to bring two innovative treatments for three potential indications to patients with unmet medical needs across Canada, thus expanding upon our foundational HIV portfolio and primary business in the U.S.,” said Paul Lévesque, President and Chief Executive Officer of Theratechnologies. “The agreement with Ionis is a testament to our team’s capabilities to advance innovation across North America and reaffirms our commitment to be a commercially focused company that delivers sustained top- and bottom-line growth and value for shareholders.” “We are pleased to partner with Theratechnologies, bringing together their deep regional expertise in Canada and our shared goal of delivering innovative new medicines to people living with severe and debilitating diseases,” said Brett Monia, Ph.D., Ionis Chief Executive Officer. “Ionis is well-positioned to deliver these medicines to the U.S. market as we rapidly approach our first anticipated independent commercial launches, assuming regulatory approvals of olezarsen in FCS and donidalorsen in HAE. Our new partnership with Theratechnologies supports our commitment to ensure access to our innovative medicines globally.” Olezarsen Olezarsen is an investigational RNA-targeted medicine designed to lower the body's production of apoC-III, a protein produced in the liver that regulates triglyceride (TG) metabolism in the blood. It is being evaluated for the treatment of both FCS and sHTG. FCS is characterized by extremely elevated TG levels, chronic, debilitating symptoms and recurrent, potentially life-threatening acute pancreatitis. Generally, the prevalence of FCS in Canada is similar to the broader global population. However, in specific regions like Eastern Québec, the prevalence of FCS is believed to be approximately 100-fold higher (1:10,000) than the global average due to the founder effect. sHTG is characterized by a severe elevation in TG levels and can result in serious health complications, including potentially life-threatening acute pancreatitis. The disease affects a much larger patient population than FCS, with a total addressable market for sHTG in the U.S. representing up to approximately 3 million patients and a similar prevalence in Canada on a per capita basis. The U.S. Food and Drug Administration (FDA) has accepted for Priority Review the olezarsen New Drug Application (NDA) for the treatment of adults with FCS. The FDA has designated olezarsen as an Orphan Drug and has set a Prescription Drug User Fee Act (PDUFA) action date of December 19, 2024. Theratechnologies plans to submit olezarsen in FCS to Health Canada for review in 2025. If the Company receives a Notice of Compliance, it will be the first approved treatment for FCS treatment in Canada. Ionis has completed enrollment of the Phase 3 olezarsen clinical program for patients with sHTG (CORE, CORE2 and ESSENCE), with results from all three trials anticipated in the second half of 2025. Donidalorsen Donidalorsen is an investigational RNA-targeted medicine designed to reduce the production of prekallikrein (PKK), a protein that plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body. HAE (Type 1 and Type 2) has a combined estimated prevalence of approximately one in 50,000 people. The FDA has recently accepted the donidalorsen NDA for review for the treatment of hereditary angioedema, with a PDUFA action date of August 21, 2025. Regulatory submissions are also progressing in Europe. Donidalorsen received Orphan Drug Designation from the FDA in 2023 and from the European Commission in 2024. Theratechnologies plans to submit donidalorsen for HAE to Health Canada for review in 2025. Transaction Information Ionis has granted Theratechnologies an exclusive license to commercialize olezarsen and donidalorsen for use in Canada. Ionis will receive a $10 million upfront payment upon execution of the agreement as well as milestone payments up to $12.75 million based on the achievement of regulatory milestones, public reimbursement, and annual sales targets. Ionis will also be entitled to receive tiered double-digit royalties on annual net sales of each medicine. Theratechnologies will be responsible for filing, obtaining and maintaining regulatory approval for olezarsen and donidalorsen in Canada. Ionis will be manufacturing and supplying both products to Theratechnologies and has granted the Company a right to manufacture both products in certain limited circumstances. The term of the licensing agreement with Ionis will continue until Theratechnologies permanently ceases commercializing all licensed products in Canada, or unless earlier terminated in accordance with customary termination provisions for transactions of this like-nature. About Theratechnologies Theratechnologies (TSX: TH) (NASDAQ: THTX) is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs. Further information about Theratechnologies is available on the Company's website at www.theratech.com, on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov. Follow Theratechnologies on Linkedin and X (Twitter). About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram. Forward-Looking Information This press release contains forward-looking statements and forward-looking information (collectively, the “Forward-Looking Statements”) within the meaning of applicable securities laws, that are based on management’s beliefs and assumptions and on information currently available to it. You can identify forward-looking statements by terms such as “may”, “will”, “should”, “could”, “promising”, “would”, “outlook”, “believe”, “plan”, “envisage”, “anticipate”, “expect” and “estimate”, or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding: (i) the top and bottom-line growth of the Company; (ii) the estimates related to the prevalence of sHTG and HAE in Canada; (iii) the time periods related to the filing of the new drug submissions for each of donidalorsen and olezarsen with Health Canada; and (iv) the time period related to the receipt of results from the Phase 3 olezarsen clinical program for patients with sHTG. Although the Forward-Looking Statements contained in this press release are based upon what the Company believes are reasonable assumptions in light of the information currently available, investors are cautioned against placing undue reliance on these statements since actual results may vary from the Forward-Looking Statements contained in this press release. Certain assumptions made in preparing the Forward-Looking Statements include that: (i) sales of the products currently sold by the Company will continue to grow; (ii) the donidalorsen and olezarsen compounds, when filed with Health Canada, will be approved by the agency; (iii) both of these compounds, if and when approved, will be reimbursed in Canada and will be accepted by the Canadian marketplace as treatment for which they will be indicated; (iv) sales of these compounds will contribute to the top and bottom-line growth of the Company; (v) we will have all of the information required to file new drug submissions for each of those compounds with Health Canada according to the timelines set forth herein; and (vi) the results from the Phase 3 olezarsen clinical program will be available to us in the second half of 2025. Forward-Looking Statements assumptions are subject to a number of risks and uncertainties, many of which are beyond the Company’s control, that could cause actual results to differ materially from those that are disclosed in or implied by such Forward-Looking Statements. These risks and uncertainties include, but are not limited to: (i) a decrease in sales of our commercialized products; (ii) the non-approval by Heath Canada of one or both of the compounds; (iii) even if approved by Health Canada, the non-reimbursement in Canada of one or both of these compounds; (iv) the non-acceptance by the marketplace of these new compounds to treat the diseases they will be indicated for; (v) competing treatments from the entry of new drug products; (vi) delays in the filing of new drug submissions for any of those compounds; (vii) unexpected expense increases in connection with our activities, including seeking the approval of, and/or commercially launching, any of those compounds; and (viii) delays in receiving the results from the Phase 3 olezarsen clinical program. The Company refers current and potential investors to the “Risk Factors” section of the Company’s Form 20-F dated February 21, 2024, available on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov under Theratechnologies’ public filings. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-Looking Statements reflect current expectations regarding future events and speak only as of the date of this press release and represent the Company’s expectations as of that date. Contacts: Media inquiries: Julie Schneiderman Senior Director, Communications & Corporate Affairs communications@theratech.com1-514-336-7800 Investor Inquiries: Philippe Dubuc Senior Vice President and Chief Financial Officer pdubuc@theratech.com438-315-6608

引进/卖出临床3期孤儿药申请上市优先审批

2024-12-02

·生物制药小编

Q3百济二股东新建仓的Biotech

上期总结了百济神州二股东Baker Brother在第三季度清仓的几家企业，本期将简单盘点Baker Brother在Q3建仓的企业，考虑到高瓴旗下的HHLR可能受到美国大选，以及大量持有中概股的影响，或许Baker Brother作为更专注于生物技术的投资机构，更能体现市场对哪些技术较为看好。 Wave Life Sciences Wave Life Sciences的看点在于首个RNA编辑疗法的概念验证，在今年10月时该公司发表了核心管线WVE-006的临床概念验证结果。 WVE-006是一款针对α-1抗胰蛋白酶缺乏症（AATD）的RNA编辑疗法候选药物，可以通过募集体内的腺苷脱氨酶（ADAR）实现对RNA的编辑，进而纠正导致蛋白质功能失调的错误。 ADAR是一种在RNA编辑和基因表达调控中发挥着关键作用的酶，能够催化RNA中特定腺苷（A）转换为肌苷（I），从而改变RNA的序列，进而影响由该RNA编码的蛋白质的结构和功能，在AATD中，由于负责编码AAT蛋白的SERPINA1等位基因碱基突变，会导致患者无法分泌足够的AAT蛋白，而招募血液中的ADAR就有望通过改变腺苷的方式来回复AAT的野生型功能，同时也会减少异常Z-AAT蛋白。 WVE-006临床结果显示在第15天时，血浆中循环的野生型M-AAT蛋白平均浓度达到6.9微摩尔，占AAT总量的60%以上。平均总AAT蛋白浓度从基线时低于可量化水平增加至第15天时的10.8微摩尔，达到了AAT增强疗法监管审批所依据的水平。这标志着人类历史上首次实现了RNA编辑的临床验证。硕迪生物硕迪生物在最近的小分子GLP-1赛道中脱颖而出，6月份公布核心管线GSBR-1290的临床数据后，公司大规模公开募股，股价迎来了一波大涨。临床研究显示，经安慰剂校正后，GSBR-1290治疗组患者体重在12周时下降了6.2%，且67%的治疗参与者实现了≥6%的体重减轻，33%的体重减轻≥10%。安全性数据则看起来要优于司美格鲁肽和替尔泊肽。从公司的现金状况来看，9.153亿美元的现金及其等价物和短期投资足够该公司运营到2027年。尽管6月份的大涨令硕迪生物股价攀升，但是近期可能受到一些外部因素影响，股价呈现出走低趋势，Baker Brother可能在这个时候选择了抄底。 Arvinas 在今年4月时，PROTAC龙头Arvinas就雄激素受体（AR）蛋白降解剂ARV-766与诺华达成了总额10.1亿美元的授权合作协议，而短短一个月过去后，在ASCO大会上，诺华的付出似乎就有了回报。新公布的临床数据中ORR达到了30%，存在CR和PR患者，安全性较既往PROTAC药物也有所提升，相比第一个推动进入临床的PROTAC小分子ARV-110更加安全。虽然药物表现很亮眼，但是从5月末以来该公司股价反响平平，可能是受到了几位大股东减持以及大盘的影响，Baker Brother选择在Q3这一季度进行抄底。 Ionis Pharmaceuticals 作为反义寡聚核酸（ASO）领域的领军企业，Ionis早早进入了商业化阶段，现金流充裕似乎不必担心生存问题，然而对于这家企业来说，问题在于收入的削减，急需要新上市产品改善收入。根据Q3财报显示，今年Q3一季度的收入同比去年同期下降了7%，这主要反映了合作方渤健SMA药物SPINRAZA收入受到Zolgensma等竞品影响而严重下滑。这使得Ionis股价也在第三季度表现平平。好在该公司还有几个新的里程碑将要实现，今年年末就是该公司降脂药APOC ASO Olezarsen的PDUFA日期，明年8月则将迎来PKK ASO donidalorsen的PDUFA日期，这对于Ionis增加新收入点至关重要。Baker Brother可能看准了该时间点选择了抄底。 Bicara Therapeutics 双抗公司Bicara Therapeutics是最近上市的Biotech企业，大股东是印度仿制药企biocon，二股东是RA资本，该公司的卖点在于核心管线EGFR/TGFβ双抗BCA101，早先PD-1/L1xTGF-β的双抗组合几乎是失败的尝试，而在这里Bicara则试图用EGFR来解决问题，有许多证据表明EGFR和TGFβ之间存在协同作用，例如说用标准治疗采用西妥昔单抗阻断EGFR会导致TGFβ分泌、上皮-间质转化过程（EMT）和癌症相关成纤维细胞（CAF）形成增加，这反过来导致西妥昔单抗耐药。 BCA101的尝试在于克服西妥昔单抗的耐药问题，简单对比的话，PD-1/L1单抗+西妥昔单抗的组合普遍报道的ORR率在40%左右，如Sacco AG等人，Guo Y等人的报道。而今年6月时Bicara公布的BCA101联合帕博利珠单抗的客观响应率为 54%，在HPV阴性这个亚群患者中ORR率更高，达到了64%。尽管如此，上市后该公司股价破发，Baker Brother可能选择在本季度进行抄底。参考来源： https://ir.ionis.com/newsroom/press-releases https://www.arvinas.com/about-us/leadership/#executive-committee https://www.sec.gov/Archives/edgar/data/1654430/000165575924000083/xslF345X05/wk-form4_1717192298.xml https://pmc.ncbi.nlm.nih.gov/articles/PMC10236157/ https://ir.bicara.com/news-releases/news-release-details/bicara-therapeutics-reports-third-quarter-2024-financial-results

临床结果ASCO会议蛋白降解靶向嵌合体基因疗法临床1期

2024-11-22

·医药观澜

预付款1000万美元，大冢制药获渐冻症寡核苷酸疗法全球权益

▎药明康德内容团队报道今日（11月22日），大冢制药（Otsuka）宣布与Ionis Pharmaceuticals达成合作，获得后者在研的反义寡核苷酸（ASO）药物ulefnersen（研发代号：ION363）的全球独家权益。该产品正在被开发用于治疗由融合肉瘤（FUS）基因突变引起的肌萎缩侧索硬化（ALS，俗称“渐冻症”）患者。根据协议条款，大冢制药将向Ionis公司支付1000万美元的预付款，并根据监管部门的批准和销售目标的实现情况支付分期付款。大冢制药将就该药申请监管批准，并在全球范围内独家生产和销售该产品。 ALS是一种严重的神经退行性疾病，患者的运动皮层、脑干和脊髓中的运动神经元会发生选择性退化，因此会逐渐丧失运动能力和呼吸功能，最终导致死亡。其中，约10%的案例属于遗传性ALS，这类患者的疾病发生与涉及不同细胞过程的数十个基因突变有关，其中一个名为FUS的基因突变发生率较高。与典型的ALS不同，FUS-ALS在年轻人中更为常见，平均发病年龄在40岁左右，其特点是疾病进展极快。研究表明，FUS蛋白参与着DNA与RNA的加工过程，在各类组织细胞中都有着重要作用。但过往的研究发现，运动神经元非常容易受到突变FUS蛋白的影响，其中DNA修复、转录和RNA剪接过程都会因此受损。 Ulefnersen由Ionis公司发现并开发，旨在通过抑制突变FUS蛋白的产生来治疗FUS-ALS。该产品每12周进行一次鞘内给药。Ionis公司正在包括日本在内的多个国家进行ulefnersen的3期临床试验。大冢制药新闻稿表示，该协议标志着大冢制药继获得遗传性血管性水肿（HAE）发作抑制药物donidalorsen在欧洲和亚洲（包括日本）的开发和销售权后，第二次从Ionis公司引进反义寡核苷酸（ASO）药物。今年11月4日，Ionis公司宣布美国FDA已经接受donidalorsen用于预防性治疗HAE的新药申请，PDUFA日期设定为2025年8月21日。根据新闻稿，大冢制药预计今年向欧洲药品管理局（EMA）提交该药的上市许可申请（MAA）。参考资料： [1]Otsuka Obtains Exclusive Global Licensing Rights from Ionis to Ulefnersen, a Potential Treatment for Amyotrophic Lateral Sclerosis Caused by Mutations in the Fused in Sarcoma Gene (FUS-ALS) .Retrieved Nov 22，2024, From https://www.otsuka.co.jp/en/company/newsreleases/2024/20241122_1.html [2]Ionis announces FDA acceptance of New Drug Application for donidalorsen for prophylactic treatment of HAE. .Retrieved Nov 4，2024, From https://ir.ionis.com/news-releases/news-release-details/ionis-announces-fda-acceptance-new-drug-application-donidalorsen 本文来由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

寡核苷酸引进/卖出申请上市临床2期临床3期

100 项与 Donidalorsen 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
遗传性血管性水肿	申请上市	美国	Ionis Pharmaceuticals, Inc.	2024-11-04

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04307381 (Corporate Publications) 人工标引	临床2期	遗传性血管性水肿	17	DonidalorsenDonidalorsen 80 mg SC Q4W	築顧淵獵鬱築製艱網繭(鹹窪夢獵醖餘蓋獵夢蓋) = 襯遞築窪築壓構獵製餘選觸構醖憲選糧簾繭襯 (鹽蓋窪願衊鏇壓網膚鏇, 7.81)	积极	2024-10-30
				Donidalorsen 80 mg SC Q8WDonidalorsen 80 mg SC Q8W	淵獵構襯膚齋選艱鹹顧(淵簾積鬱構鏇遞觸淵窪) = 繭憲網鹽鑰廠廠糧醖夢遞艱憲遞壓醖網鹹艱糧 (鹽醖齋願襯蓋繭願繭廠 ) 更多
NCT05139810 (OASIS-HAE, Pubmed) 人工标引	临床3期	遗传性血管性水肿	90	Donidalorsen 80 mg every 4 weeks	餘窪簾鹹艱壓鬱範積繭(餘築蓋範醖鏇膚製鏇簾) = 鹹壓憲餘範憲繭簾範齋艱壓鑰鑰觸遞選範膚蓋 (簾襯壓範鏇淵蓋鹽壓願, 0.27 ~ 0.73) 更多	积极	2024-07-04
				Donidalorsen 80 mg every 8 weeks	餘窪簾鹹艱壓鬱範積繭(餘築蓋範醖鏇膚製鏇簾) = 廠醖製餘膚廠憲鑰獵鹹艱壓鑰鑰觸遞選範膚蓋 (簾襯壓範鏇淵蓋鹽壓願, 0.65 ~ 1.59) 更多
NCT04307381 (OASISplus, Company_Website) 人工标引	临床2期	遗传性血管性水肿	83	Donidalorsen every four weeks (Open-Label Extension Cohort)	壓選製淵襯糧餘膚願積(齋網積獵糧艱窪顧壓衊) = None 繭齋鹹鹹糧艱夢繭鹽糧 (襯積淵鹹糧願鹽鹽鏇艱 )	积极	2024-05-31
				Donidalorsen every eight weeks (Open-Label Extension Cohort)
NCT05139810 (OASIS-HAE, Company_Website) 人工标引	临床3期	遗传性血管性水肿	90	donidalorsen 80 mg Q4W	淵壓鏇構襯醖鑰遞淵鏇(簾選鏇範鹽鏇餘範齋簾) = 遞願獵選鬱衊齋網顧鹹獵選鬱鹽窪襯選醖夢範 (艱膚鹹鹽壓繭淵襯願壓 ) 达到	积极	2024-05-31
				donidalorsen 80 mg Q8W	淵壓鏇構襯醖鑰遞淵鏇(簾選鏇範鹽鏇餘範齋簾) = 願繭顧膚膚廠選壓積壓獵選鬱鹽窪襯選醖夢範 (艱膚鹹鹽壓繭淵襯願壓 ) 达到
NCT04307381 (AAAAI2024) 人工标引	临床2期	遗传性血管性水肿 Type 1/2 hereditary angioedema	17	Donidalorsen 80 mg Q4W	獵衊網選淵齋鑰遞醖衊(鏇艱簾選鹹構淵醖製鑰) = No serious treatment-emergent adverse events (TEAEs) or TEAEs leading to treatment discontinuation were reported after 2 years. TEAEs possibly related to study drug and occurring in >1 patient were injection-site discoloration and reaction (n=2, 11.8% each). 壓齋築艱願淵齋蓋鏇簾 (鹹憲夢襯願製顧窪衊襯 ) 更多	积极	2024-02-23
NCT05139810 (OASIS-HAE, PRNewswire) 人工标引	临床3期	遗传性血管性水肿	91	donidalorsen	範願淵繭鹹繭艱淵膚積(選選廠憲憲憲願積淵壓): P-Value = <0.001 更多	积极	2024-01-22
				placebo
NCT04030598 (ISIS 721744-CS2, ACAAI2023) 人工标引	临床2期	遗传性血管性水肿	17	donidalorsen	鹽製遞築蓋淵簾構淵獵(範醖簾糧願選繭遞淵簾) = 鹽齋鑰衊製鏇遞觸淵遞鑰顧築餘觸獵願衊獵蓋 (艱艱遞顧餘製淵襯壓膚 )	积极	2023-11-09
NCT04307381 (ISIS 721744-CS3, AAAAI2023)	临床2期	遗传性血管性水肿	17	Donidalorsen 80 mg every 4 weeks	衊醖遞糧網廠築鏇淵廠(衊鏇網觸鹽蓋淵築繭築) = AE-QoL total score improved from baseline to after 1 year of treatment by a mean change of 24.0, with improvements observed in all domains 廠餘膚壓窪獵壓壓鹹築 (觸膚醖鹹蓋範鹹齋願膚 ) 更多	积极	2023-02-01
NCT04307381 (PRNewswire) 人工标引	临床2期	遗传性血管性水肿	17	donidalorsen	糧鏇衊顧蓋積製淵襯鑰(選醖築壓襯構衊糧淵廠) = 衊艱憲餘廠網糧鹹襯夢衊襯窪積廠淵積壓醖壓 (醖憲獵艱鑰壓憲築積構 ) 更多	积极	2022-11-13
NCT04030598 (ISIS 721744-CS2, CTgov)	临床2期	遗传性血管性水肿	23	Placebo (Part A: Placebo)	鹽遞選鑰範構鹹膚選顧(衊窪構醖襯繭淵顧網網) = 範鬱齋夢蓋餘衊夢鬱憲醖願鹹憲願壓遞淵餘蓋 (蓋襯醖鏇夢膚網獵鏇淵, 憲構觸鬱獵顧齋醖顧鑰 ~ 獵願網鏇糧夢壓鏇廠窪) 更多	-	2022-09-28
				Donidalorsen (Part A: Donidalorsen 80 mg)	鹽遞選鑰範構鹹膚選顧(衊窪構醖襯繭淵顧網網) = 艱糧積鏇構選醖構夢糧醖願鹹憲願壓遞淵餘蓋 (蓋襯醖鏇夢膚網獵鏇淵, 製膚餘繭襯積壓範獵鏇 ~ 鹽夢壓衊遞餘顧壓鏇構) 更多