Direct oral anticoagulants (DOAC) have emerged as safe and efficacious ischemic stroke prophylaxis for non-valvular atrial fibrillation (NVAF). All four DOACs - apixaban, dabigatran, edoxaban, rivaroxaban - were associated with lower risks of major bleeding compared to warfarin. Listed as core essential medicines by the World Health Organization, DOAC prescriptions have been surging worldwide. In Hong Kong, approximately 80,000 patients received DOACs from January 2009 through December 2022 according to the Hospital Authority registry.
The widespread DOAC usage had created DOAC-specific clinical dilemmas that lack evidence-based treatment despite twenty years of prescribing experience. Ischemic stroke despite DOAC (IS-DOAC), in particular, may occur in up to 6% of DOAC users annually. Due to the in vivo anticoagulation effect, there had been concerns of intracerebral bleeding (ICH) with intravenous thrombolytic therapy (IVT) for acute IS-DOAC. Under the current guideline recommendations, most acute IS-DOAC are contraindicated to IVT (see Intravenous thrombolytic therapy), which resulted in only a small proportion of acute ISDOAC patients being able to receive IVT even if presented early. Nonetheless, our group found that majority of patients had a DOAC level of <50ng/mL only 24 hours after DOAC cessation (see work done by us), a level deemed clinically negligible and safe for thrombolytic therapy. Together with evolving clinical evidence discussed below, IS-DOAC patients maybe unnecessarily barred from IVT, thus compromised functional recovery.
With robust pharmacokinetic and retrospective clinical evidence to support, it is hypothesized that IVT are safe in IS-DOAC patient. The investigators hereby propose a prospective multicenter study to determine the efficacy and safety of IVT in acute IS-DOAC.

开始日期2024-03-05

申办/合作机构

香港中文大学

[+6]

NCT06194968 / RecruitingN/AIIT

Treatment of Acute Ischemic StroKe With Intravenous UroKinase Real-world Research: a Multicenter, Prospective Study (TASK-UK)

The purpose of this study is to to compare the safety and effectiveness of IV urokinase with IV alteplase in the treatment of AIS in patients up to 6 hours from symptom onset.

开始日期2023-12-30

申办/合作机构

郑州大学第一附属医院

[+1]

NCT06115070 / Recruiting临床4期

ALteplase for the Treatment of Acute Ischemic Stroke in Patients With LOW National Institutes of Health Stroke Scale and Specified Disabling Deficits

About 1/3 patients with mild stroke have poor prognosis, whether patients with this type undergo thrombolysis has been a controversial issue. A pooled analysis published in the Lancet in 2014 included 9 high-quality RCT studies of intravenous thrombolysis such as NINDS and IST3, and a total of 666 (10%) patients with mild stroke were included in the analysis. For mild stroke, the proportion of good prognosis in the control group and the alteplase group was 58.9% and 68.7% (OR 1.48, 95%Cl 1.07-2.06), respectively. Therefore, guidelines recommended alteplase thrombolytic therapy for patients with mild stroke. However, PRISMS, a randomized controlled trial of intravenous thrombolytic therapy for mild stroke published in 2018, found that alteplase intravenous thrombolytic therapy did not improve clinical outcomes compared with aspirin in patients with mild non-disabled stroke (90-day mRS 0-1 ratio 78.2% vs 81.5%), and the incidence of symptomatic intracranial hemorrhage was higher. However, a major limitation of the PRISMS study was that more than 85% of patients had numbness and dysarticulation, so this conclusion cannot be extrapolated to patients with other mild stroke symptoms. Moreover, due to the early termination of the sponsorship of this trial, the number of enrolled cases did not reach the pre-designed number, resulting in a serious decline in the authenticity of the study results.
Symptoms and outcomes of minor stroke are important criteria for assessment. However, there is currently no uniform standard for the assessment of disability. Therefore, the center developed a mild stroke EMSS assessment scale to refine the disability assessment of stroke symptoms. It was found that intravenous thrombolytic therapy was safe and effective for patients with symptoms such as dizziness, disorientation, memory impairment, decreased muscle strength at the proximal end of one limb, and ataxia while standing.
Therefore, the purpose of this study was to investigate whether ischemic stroke patients with onset or detection time within 4.5 hours, and mild stroke patients with NIHSS score ≤5 with any of the following symptoms: dizziness, disorientation, memory impairment, single proximal muscle strength decline, or ataxia while standing could benefit from intravenous thrombolysis based on CT/MRI screening in the Chinese population.

开始日期2023-11-17

申办/合作机构

浙江大学医学院附属第二医院

100 项与阿替普酶相关的临床结果

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100 项与阿替普酶相关的转化医学

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100 项与阿替普酶相关的专利（医药）

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14,206

项与阿替普酶相关的文献（医药）

2024-12-31·Annals of medicine

Effects of intravenous rtPA in patients with minor stroke

Article

作者: Hu, Shiyu ; Lei, Zhihao ; Li, Shuanglin ; Feng, Hongye ; Li, Jun ; Wu, Xiaohong ; Pan, Suyue ; Ren, Lijie ; Xu, Gelin

BACKGROUND:

Whether minor ischemic stroke (MIS) patients can benefit from intravenous thrombolysis (IVT) remains controversial. The association between the efficacy of IVT and baseline National Institute of Health Stroke Scale (NIHSS) score is unclear in MIS, while the association in moderate and severe stroke is known. This study aimed to explore the effect of IVT in patients with MIS and analyze its efficacy in patients with different baseline NIHSS scores.

METHODS:

Patients with a NIHSS score ≤5 within 4.5 h of stroke onset were screened in 32 centers. Patients with and without IVT were matched to a ratio of 1:1 with propensity scores. An excellent outcome was defined as a modified Rankin Scale (mRS) score ≤1 at three months after stroke onset. Safety outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Multivariate analysis was used to compute the adjusted odds ratio (OR) for excellent outcomes. The effect of IVT was further analyzed in subgroups according to the baseline NIHSS score.

RESULTS:

Of the 23,853 screened, 3336 patients with MIS who arrived at the hospital within 4.5 h of onset were included. The 1163 patients treated with IVT were matched with 1163 patients without IVT. IVT in minor strokes generated an adjusted OR of 1.38 (95% CI: 1.09-1.75, p = 0.009) for excellent outcomes. There were no significant differences in mortality (0.17% vs. 0.09%, p = 1.000) and sICH (0.69% vs. 0.86%, p = 0.813) between patients with and without IVT. Subgroup analysis showed that there was no significant effect of IVT in the baseline NIHSS 0-1 or 2-3 subgroups, with adjusted OR of 0.816 (95% CI 0.437-1.53, p = 0.525) and1.22 (95% CI 0.845-1.77, p = 0.287), respectively. In patients with NIHSS score of 4-5, IVT was significantly effective, with an adjusted OR of 1.53 (95% CI 1.02-2.30, p = 0.038).

CONCLUSION:

IVT can improve MIS outcomes. The risks of sICH and mortality did not increase, especially in patients with NIHSS scores 4 to 5, who could benefit from IVT significantly.

2024-07-01·Current reviews in clinical and experimental pharmacology

Intrapleural Thrombolytics for Parapneumonic Effusion: A Network Metaanalysis

Article

作者: Sridharan, Kannan ; Sivaramakrishnan, Gowri

Objectives::

Intrapleural thrombolytics have been trialed for facilitating pleural fluid drainage in patients with complicated parapneumonic effusion. The present study is a network metaanalysis of randomized clinical trials (RCTs) that have evaluated these thrombolytics.

Methods::

Electronic databases (Medline, Cochrane CENTRAL, and Google Scholar) were searched for appropriate RCTs evaluating the therapeutic effect of thrombolytics in patients with complicated parapneumonic effusion. Mortality, the proportion of patients referred for surgical intervention, and serious adverse events were the outcome measures. Random-effects model was used for generating direct and mixed treatment comparison pooled estimates. Grading of the evidence for key comparisons was carried out. Odds ratio with 95% confidence intervals was used to represent the pooled estimates.

Results::

Seventy-six studies were retrieved with the search strategy, of which 16 were included. No significant differences were observed in mortality. Compared to normal saline, significantly less proportion of patients was referred for surgical intervention with streptokinase (0.4, 0.2 to 0.8), urokinase (0.4, 0.2 to 0.8), alteplase (0.3, 0.1 to 0.7), and alteplase + DNase (0.2, 0.1 to 0.7). DNase alone increased the risk of referral to surgical intervention (3.4, 1.5 to 7.6). Only streptokinase was observed with an increased risk of serious adverse events compared to normal saline (2.8, 1.1 to 7.1) and alteplase (6.7, 1.1 to 39.9). Moderate quality of evidence was observed for streptokinase with normal saline for the proportion of patients referred for surgical intervention, while either low or very low quality strength was observed for all other comparisons.

Conclusion::

Streptokinase, urokinase, alteplase, and alteplase + DNase were observed in patients referred for surgical interventions when used intrapleural in patients with parapneumonic effusion. Alteplase + DNase is likely to outperform others as it was observed with the least risk of patients referred for surgical interventions. Until additional data emerges that changes the pooled estimates, thrombolytics other than streptokinase are preferred due to the increased risk of serious adverse events.

2024-05-01·Critical care medicine

Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study*

Article

作者: Gajic, Ognjen ; Brown, Caitlin S ; Melamed, Roman ; Sidebottom, Abbey ; Tierney, David M ; Xia, Ranran ; Mara, Kristin C ; Lillyblad, Matthew ; Khapov, Ivan ; Wiley, Brandon M

OBJECTIVES::

Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens.

DESIGN::

Multicenter retrospective observational study.

SETTING::

Tertiary care hospital and 15 community and academic centers of a large healthcare system.

PATIENTS::

Hospitalized patients with PE treated with systemic alteplase.

INTERVENTIONS::

None.

MEASUREMENTS AND MAIN RESULTS::

Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively (p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting.

CONCLUSIONS::

In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

101

项与阿替普酶相关的新闻（医药）

2024-06-25

·BioSpace

NervGen Pharma to Advance NVG-300 into Preclinical Proof-of-Concept Stage

New molecule demonstrates efficacy in a challenging SCI model Expanding pipeline into new indications of ischemic stroke and ALS Vancouver, British Columbia--(News - June 25, 2024) - NervGen Pharma Corp. (TSXV: NGEN) (OTCQB: NGENF), a clinical-stage biotech company dedicated to developing innovative solutions for the treatment of nervous system damage, today announced its plans for the development of a new drug candidate, NVG-300, with a focus on three initial indications: ischemic stroke, amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI). NVG-300 is a new biologic molecule discovered at NervGen. Pending successful preclinical validation, NVG-300 will be developed under the Biologics License Application regulatory framework providing 12 years of market exclusivity post-approval. NVG-300's composition of matter intellectual property protection is expected to extend beyond 2040. The discovery of NVG-300 is the result of a research effort initiated by NervGen in 2022, leveraging the extensive internal expertise and the evolving scientific understanding of the mechanisms involved in nervous system repair. NVG-300 is the first of what the company believes will be a pipeline of new molecules addressing high unmet need neurologic indications. NVG-300 product and process development have progressed to successfully establish manufacturability and feasibility of high concentration liquid formulation to enable self-administration of the product in a prefilled syringe format. "We are excited to advance NVG-300 toward development based on promising efficacy observed in a model of SCI characterized by heightened severity of spinal cord damage and impaired spontaneous recovery," said NervGen's Vice President of Research and Preclinical Development, Dr. Matvey Lukashev. "Based on these results, we are conducting formulation development, advancing further preclinical evaluation of NVG-300 in SCI and initiating efficacy studies in preclinical models of ischemic stroke and ALS. The results from these preclinical studies are expected in early 2025." "Early signs of preclinical efficacy and favorable pharmaceutical properties provided the evidence we needed to advance NVG-300 into expanded indications characterized by nervous system damage," said Mike Kelly, NervGen's President and CEO. "While our lead product candidate, NVG-291, remains the key focus of the company, we expect NVG-300 to add diversity to our pipeline and provide strategic optionality for future partnering opportunities. As a pioneer and an emerging leader in the development of pharmacological interventions targeting the mechanisms that inhibit nervous system repair, we focus our research and development efforts to ensure we remain at the forefront of this exciting new therapeutic field." About Ischemic Stroke Stroke is the leading cause of death and severe disability worldwide, significantly diminishing the quality of life for many affected individuals. Globally, nearly 17 million people experience a stroke each year, with over two million cases annually in the United States, Europe, and Japan combined. The most prevalent type of stroke, ischemic stroke, occurs when a blockage in the brain's blood flow deprives it of oxygen and nutrients, often leading to long-term or permanent neurological damage. Unfortunately, treatment options for ischemic stroke are limited. Current therapies, such as the administration of the clot-dissolving agent tissue plasminogen activator or surgical clot removal, must generally be performed within a few hours of stroke onset. About Amyotrophic Lateral Sclerosis (ALS) ALS is an invariably fatal progressive neurodegenerative disorder caused by loss of motor neurons and resulting in loss of voluntary muscle function, culminating in respiratory paralysis and death, usually within 2-5 years after diagnosis. Roughly 1 in 400 people will develop ALS in their lifetime. There are an estimated 30,000 people in the United States and more than 30,000 people in Europe (European Union and United Kingdom) living with ALS at any given time. About Spinal Cord Injury (SCI) SCI resulting from trauma causes disruption of the signals normally transmitted between the brain and the body, frequently resulting in severe functional impairment below the level of the injury. Every year, up to 500,000 people globally suffer from SCI. Each individual with SCI faces an expected lifetime cost of care between $1M and $4M, depending on severity and age at injury. Existing treatments are limited to surgical stabilization and physical rehabilitation, which result in partial improvement. There are currently no U.S. Food and Drug Administration-approved treatments that can promote repair and improve function following SCI. About NervGen NervGen (TSXV: NGEN) (OTCQB: NGENF) is a clinical-stage biotech company dedicated to developing innovative treatments that enable the nervous system to repair itself following damage, whether due to injury or disease. NervGen's lead drug candidate, NVG-291, is currently being evaluated in a Phase 1b/2a clinical trial in the company's initial target indication, spinal cord injury. For more information, visit or follow NervGen on X, LinkedIn, and Facebook for the latest news on the company. Contacts Huitt Tracey, Investor Relations htracey@nervgen.com 604.362.6209 Bill Adams, Chief Financial Officer info@nervgen.com 778.731.1711 David Schull or Ignacio Guerrero-Ros, Ph.D. Russo Partners david.schull@russopartnersllc.com ignacio.guerrero-ros@russopartnersllc.com 858.717.2310 646.942.5604 Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. Cautionary Note Regarding Forward-Looking Statements This news release may contain "forward-looking information" and "forward-looking statements" within the meaning of applicable Canadian and United States securities legislation. Such forward-looking statements and information herein include, but are not limited to, the Company's current and future plans, expectations and intentions, results, levels of activity, performance, goals or achievements, or any other future events or developments constitute forward-looking statements, and the words "may", "will", "would", "should", "could", "expect", "plan", "intend", "trend", "indication", "anticipate", "believe", "estimate", "predict", "likely" or "potential", or the negative or other variations of these words or other comparable words or phrases, are intended to identify forward-looking statements. Forward-looking statements include, without limitation, statements relating to: the development plans and timelines for NVG-300; the objectives, study design, planned clinical endpoints, timing, expected rate of enrollment and data readout of our Phase 1b/2a clinical trial in individuals with spinal cord injury; future plans for our pipeline development; the belief that targeting mechanisms that interfere with nervous system repair is a promising target for reducing the clinical effects of nervous system damage through multiple mechanisms; and the creation of innovative treatments of nervous system damage due to trauma or disease. Forward-looking statements are based on estimates and assumptions made by the Company in light of management's experience and perception of historical trends, current conditions and expected future developments, as well as other factors that we believe are appropriate and reasonable in the circumstances. In making forward-looking statements, the Company has relied on various assumptions, including, but not limited to: the Company's ability to manage the effects of pandemics such as COVID-19; the accuracy of the Company's financial projections; the Company obtaining positive results in its clinical and other trials; the Company obtaining necessary regulatory approvals; and general business, market and economic conditions. Many factors could cause our actual results, level of activity, performance or achievements or future events or developments to differ materially from those expressed or implied by the forward-looking statements, including without limitation, a lack of revenue, insufficient funding, the impact of pandemics such as the COVID-19, reliance upon key personnel, the uncertainty of the clinical development process, competition, and other factors set forth in the "Risk Factors" section of the Company's Annual Information Form, Prospectus Supplement, financial statements and Management Discussion and Analysis which can be found on SEDARplus.ca. All clinical development plans are subject to additional funding. Readers should not place undue reliance on forward-looking statements made in this news release. Furthermore, unless otherwise stated, the forward-looking statements contained in this news release are made as of the date of this news release, and we have no intention and undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement. To view the source version of this press release, please visit

2024-06-24

·Science Daily

Standardized protocols help hospitals treat strokes faster

Research illustrates that American Heart Association and American Stroke Association guidelines are effective at speeding up hospitals' response times for stroke treatment and can be mastered even by members of 'ad hoc' medical teams that assemble rapidly on the fly. West Virginia University research illustrates that American Heart Association and American Stroke Association guidelines are effective at speeding up hospitals' response times for stroke treatment and can be mastered even by members of "ad hoc" medical teams that assemble rapidly on the fly. Swift stroke treatment is critical, so when a stroke patient arrives at an emergency room, specialists from across hospital departments -- EMS, neurologists, pharmacists, physicians, nurses, radiologists and technicians -- rush to coordinate a team response. AHA and ASA guidelines, or "best practices," put specific limits on how much time can optimally elapse between the onset of ischemic stroke, in which blood flow to the brain is blocked, and subsequent events like arrival at the hospital and delivery of an infusion. However, experts have questioned whether the communication of those best practices helps medical teams that assemble temporarily and whose members don't typically collaborate. A Journal of Operations Management paper by WVU John Chambers College of Business and Economics associate professor Bernardo Quiroga and coauthors answers that question using data about more than 8,000 patients who received stroke care at a large hospital (not WVU Hospitals) between 2009 and 2017. "'Time is brain' for stroke victims," Quiroga explained. "Blocked blood flow to the brain kills almost two million neurons a minute, so your life or ability to walk or talk hinges on how quickly multiple professionals coordinate to restore blood flow. If you're lucky, you're treated within the first hour of symptom onset. Better yet, you receive a shot of Tissue Plasminogen Activator, which dissolves clots. TPA works better the earlier it's given and usually isn't effective after 4.5 hours." In 2010, the AHA and ASA launched Target: Stroke, a program that identifies stroke care best practices and standardizes each step in the process. Participating hospitals reduced median treatment times from 79 minutes in 2009 to 51 minutes in 2017, but it wasn't clear if that improvement was driven by adherence to best practices or by clinicians learning through repetition as they handled more stroke cases. To figure that out, the researchers investigated whether repeated "learning by doing" decreased the hospital's stroke care time. Then, they evaluated whether deliberate, "induced" learning and implementation of AHA/ASA best practices decreased the time further. Learning through repetition worked. The more strokes the hospital treated, the faster it responded. For each doubling of cumulative stroke alerts, "door-to-needle time" -- the time to get patients from the hospital door to a TPA infusion -- decreased by 10.2%. Best practices also worked. Specifically, the researchers examined two best practices: the Helsinki Model protocol, which directs that EMS staff keep stroke patients on the stretcher for transport to the CT room rather than transferring them to ER beds; and the Rapid Administration of TPA protocol, which requires the pharmacist to be in the CT room with TPA before completion of the CT scan. Those protocols significantly reduced the hospital's door-to-needle time beyond improvements from repetition-based learning. According to Quiroga's coauthor and former PhD student Brandon Lee, that matters because it demonstrates the efficacy of best practices and shows ad hoc teams learning guidelines and implementing them long-term. However, Lee emphasized the importance of the presence of the hospital's stroke advisory committee, which set targets, evaluated stroke teams' performances and gave feedback. Without similar "countermeasures to organizational forgetting," Quiroga acknowledged that best practices aren't always sustainable, especially on ad hoc teams. "In the case of the best practice indicated by the Helsinki Model, compliance is difficult because the hospital needs to coordinate with multiple independent EMS systems. Some EMS providers may be reluctant to commit resources to extended time in the CT room, and EMS staff turnover may lead to forgetting," Quiroga said. Lee added, "Overall, because ad hoc teams are fluid, information sharing is harder. And when a group of people don't know each other well, group learning slows. But although ad hoc teams learn more slowly, we determined they still learn." The research also assessed whether neurologists' abilities to meet time goals were affected by their recent experiences treating prior stroke patients. "As team leaders, neurologists can have an outsized influence on performance," Quiroga said. "Because other members of the ad hoc team aren't familiar with each other, they lean on their leader." But data showed stroke teams improving response times regardless of how many stroke cases the neurologist had treated individually or what the neurologist's recent success rate was. Quiroga said that's good news. "The implication is that learning and sustaining best practices ensures an even quality of care for patients, regardless of individual neurologists' experience levels."

AHA会议

2024-06-23

·医药观澜

20多款1类新药在中国获批临床，来自辉瑞、默沙东、海思科等公司

▎药明康德内容团队报道根据中国国家药监局药品审评中心（CDE）官网公示，近两周以来，有20余款1类新药首次获得临床试验默示许可（IND）。通过梳理，这些新药涵盖小分子新药、分子胶、抗体偶联药物（ADC）、单抗、三抗等，涉及靶点包括了DGKα、LSD1、THR-β、DHX33、KRAS G12D、CD38等等。本文将对其中部分产品进行简要介绍。海思科：HSK42360片作用机制：BRAF V600抑制剂适应症：BRAF V600突变晚期实体瘤根据海思科公告介绍，HSK42360是该公司自主研发的一种靶向BRAF V600突变且具有脑透性的小分子抑制剂，临床拟用于治疗BRAF V600突变晚期实体瘤。临床前研究结果显示，HSK42360在多个BRAF V600突变的实体瘤药效模型中展现出较好的抗肿瘤药效，同时也表现出了良好的耐受性和较大的安全窗，是一款具有开发潜力的小分子抗肿瘤药物。 CASI Pharmaceuticals：CID-103注射液作用机制：抗CD38单抗适应症：多发性骨髓瘤 CID-103是凯信远达（CASI）在研的一款可特异性识别人CD38表位的单克隆抗体，可通过激活效应T细胞和NK细胞来达到杀死肿瘤细胞的目的。该产品本次在中国获批临床，适用于既往接受治疗的复发和难治性多发性骨髓瘤（R/R MM）成年患者的治疗。值得一提的是，凯信远达于2022年5月与天石同达医药达成合作，授予后者CID-103用于治疗自身免疫疾病的全球独家许可权。开悦生命：KY386注射用浓溶液作用机制：DHX33抑制剂适应症：DHX33阳性恶性肿瘤根据开悦生命新闻稿介绍，KY386注射用浓溶液是该公司自主研发的一款高效、选择性的新型DHX33抑制剂，本次获批临床的适应症为DHX33阳性的复发/难治性晚期恶性肿瘤。DHX33是一种细胞内的RNA解旋酶家族蛋白，具有促进细胞增殖作用，在癌症的发病机制上发挥着重要作用。开悦生命在RNA解旋酶药物研发领域有逾十年的基础研究经验。辉瑞：PF-07264660注射液、PF-07275315注射液作用机制：三抗适应症：特应性皮炎辉瑞（Pfizer）两款1类新药获批临床，二者均拟开发治疗成人中度至重度特应性皮炎。根据辉瑞公开资料，这两款产品均为三特异性抗体，其中PF-07264660为抗IL-4/IL-13/IL-33三抗，PF-07275315为抗IL-4/IL-13/TSLP三抗。这两款三特异性抗体在更有效阻断IL-4/IL-13信号通路的同时，可以通过抑制TSLP产生更广泛的效果，或者通过抑制IL-33通路进一步抑制瘙痒，有望对治疗特应性皮炎产生更好的疗效。百时美施贵宝：golcadomide胶囊作用机制：分子胶适应症：大B细胞淋巴瘤百时美施贵宝旗下新基（Celgene）公司1类新药golcadomide胶囊获批临床，拟开发用于未经治的高危大B细胞淋巴瘤。这是一款新型E3泛素连接酶Cereblon（CELMoD）分子，针对疾病特点做了优化，使其主要分布在淋巴器官。在针对B细胞淋巴瘤的1/2期临床研究中，该产品的客观缓解率（ORR）达到91.1%。截至目前，百时美施贵宝公司已有多款分子胶新药在中国获批或启动3期临床。默沙东：bomedemstat胶囊作用机制：LSD1抑制剂适应症：原发性血小板增多症 Bomedemstat胶囊（MK-3543）是一款口服赖氨酸特异性脱甲基酶1（LSD1）抑制剂。2022年11月，默沙东（MSD）以约13.5亿美元现金收购Imago公司，从而获得后者这款处于2期临床阶段的主要候选药物。该产品本次在中国获批临床，拟开发治疗原发性血小板增多症。LSD1是一种表观遗传调节蛋白，可调节骨髓干细胞的成熟，亦在许多血液肿瘤中扮演重要角色，被认为是治疗许多高死亡率血液肿瘤的新兴靶点之一。拜耳：BAY 2862789口服溶液、BAY 3018250 作用机制：DGKα抑制剂、抗a2AP的蛋白质药物适应症：晚期实体瘤、脑卒中拜耳（Bayer）公司两款1类新药在中国获批临床。BAY 2862789口服溶液为一款小分子DGKα抑制剂，拟用于治疗晚期实体瘤，DGKα特异性抑制剂治疗癌症有望发挥抑制癌细胞增殖、同时激活T细胞功能的双重抗癌作用。BAY 3018250为一款抗a2AP的蛋白质类药物，拟用于治疗急性缺血性脑卒中。α2-抗纤溶酶（a2AP）是一种纤溶酶抑制剂，与缺血性卒中、组织纤溶酶原激活剂（rt-PA）治疗失败的风险增加有关。安斯泰来：ASP3082注射液作用机制：KRAS G12D蛋白降解剂适应症：KRAS G12D突变实体瘤安斯泰来（Astellas）在研的ASP3082注射液在中国获批临床，拟开发用于携带KRAS G12D突变的既往经治局部晚期（不可切除）或转移性恶性实体瘤。这是一款具有高效选择性的新型KRAS G12D蛋白降解剂，它结合并选择性靶向KRAS G12D突变蛋白，通过募集E3泛素连接酶蛋白进行降解。该产品正在国际范围内开展1期临床研究。劲方医药：GFH375片作用机制：KRAS G12D蛋白降解剂适应症：KRAS G12D突变实体瘤劲方医药在研的口服KRAS G12D（ON/OFF）抑制剂GFH375片获批临床，拟开发治疗KRAS G12D突变阳性的晚期实体瘤患者。该产品通过非共价形式结合KRAS G12D蛋白，抑制其与下游效应蛋白结合，最终高效抑制肿瘤细胞增殖。2023年8月，劲方医药与Verastem Oncology达成一项超6亿美元合作，后者获得三款由劲方医药开发的靶向RAS通路创新疗法在大中华区之外的全球开发和商业化权利，其中就包括了这款GFH375。图片来源：123RF 凯思凯迪：CS060304片作用机制：新型THR-β激动剂适应症：非酒精性脂肪性肝炎凯思凯迪在研的1类新药CS060304片获得临床试验默示许可，拟开发治疗非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NASH，又称MASH）。这是一款靶向甲状腺激素受体β（THR-β）的小分子激动剂，可高度特异性富集于肝组织。该产品呈现出积极突出的临床前数据，尤其在NASH小鼠模型中可明显改善NAS评分和纤维化，具有起效剂量低、药效显著且耐受性良好的特点。征祥医药：ZX-8177片作用机制：ENPP1抑制剂适应症：晚期实体瘤征祥医药在研的小分子ENPP1抑制剂ZX-8177片获批临床，拟开发治疗晚期实体瘤。ENPP1全称为外核苷酸焦磷酸酶/磷酸二酯酶-1，可水解细胞外2'3'-cGAMP，减弱免疫刺激肿瘤微环境，从而促进肿瘤进展。因此，在肿瘤环境中阻断ENPP1是一种通过改善先天免疫反应来对抗肿瘤的潜在策略。除了上述产品，近两周还有其他1类新药在中国首次获批IND，比如恒瑞医药两款1类新药HRS-7249注射液和HRS-9813片获批临床，分别拟用于治疗高脂血症和特发性肺纤维化；百利天恒的ADC产品BL-M17D1、科伦博泰的ADC产品注射用SKB518获批临床，拟开发治疗实体瘤等等，限于篇幅，此处不再一一介绍。希望这些1类新药后续临床研究进展顺利，早日取得突破，造福患者。参考资料： [1]中国国家药监局药品审评中心（CDE）官网.Retrieved June 22，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]各公司官网及公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。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。

临床申请抗体药物偶联物申请上市临床1期细胞疗法

100 项与阿替普酶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02837	阿替普酶	B01AD02 S01XA13	DB00009

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
心肌梗塞	日本	Mitsubishi Tanabe Pharma Corp.	1991-03-29
心肌梗塞	日本	Kyowa Kirin Co., Ltd.	1991-03-29
脑卒中	日本	Kyowa Kirin Co., Ltd.	1991-03-29
脑卒中	日本	Mitsubishi Tanabe Pharma Corp.	1991-03-29
急性缺血性卒中	美国	Genentech, Inc.	1987-11-13
急性心肌梗塞	美国	Genentech, Inc.	1987-11-13
肺栓塞	美国	Genentech, Inc.	1987-11-13

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
新型冠状病毒感染	临床3期	奥地利	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	比利时	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	巴西	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	法国	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	德国	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	印度	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	意大利	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	马来西亚	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	墨西哥	Boehringer Ingelheim GmbH	2020-12-16
新型冠状病毒感染	临床3期	荷兰	Boehringer Ingelheim GmbH	2020-12-16

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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


NCT01827046 (MISTIE-III, Pubmed)	临床3期	脑出血	499	Minimally Invasive Surgery plus Alteplase (MIS+alteplase)	遞鏇製襯衊廠網願築艱(築齋鏇齋憲製襯淵憲糧): P-Value = 0.007 更多	不佳	2024-04-26
				alteplase
NCT04640194 (CTgov)	临床2/3期	新型冠状病毒感染 \| 急性呼吸窘迫综合征	104	Standard of care+Alteplase low dose (Part 1: Alteplase Low Dose)	糧齋鬱夢衊顧鏇製蓋齋(觸醖簾製繭鑰蓋築鹹壓) = 獵鬱鹽淵鹹築鏇餘壓餘餘簾憲壓製淵艱鏇鏇淵 (鹹膚餘糧選餘築窪艱選, 網膚齋積夢艱網顧鑰醖 ~ 醖繭願憲蓋糧簾餘餘糧) 更多	-	2024-03-07
				Standard of care+Alteplase high dose (Part 1: Alteplase High Dose)	糧齋鬱夢衊顧鏇製蓋齋(觸醖簾製繭鑰蓋築鹹壓) = 簾鹽膚衊憲糧鑰衊獵願餘簾憲壓製淵艱鏇鏇淵 (鹹膚餘糧選餘築窪艱選, 獵網網構顧鏇壓網壓糧 ~ 衊襯遞鬱醖願蓋積憲網) 更多
NCT03889249 (AcT trial, Pubmed)	临床3期	急性缺血性卒中	1,577	Alteplase	餘憲淵願製襯艱淵襯窪(淵衊鏇選蓋鏇鏇淵蓋蓋) = 遞憲選繭艱鹽簾廠膚鬱夢餘鑰選網壓鏇鹽網選 (艱衊艱選膚艱壓艱糧壓 ) 更多	积极	2024-02-01
				Tenecteplase	餘憲淵願製襯艱淵襯窪(淵衊鏇選蓋鏇鏇淵蓋蓋) = 製窪蓋選構鑰糧醖鹹醖夢餘鑰選網壓鏇鹽網選 (艱衊艱選膚艱壓艱糧壓 ) 更多
DEVT and RESCUE BT (ISC2023)	N/A	急性缺血性卒中	467	EVT-alone	獵繭鏇網廠夢鑰淵蓋廠(淵淵糧憲夢齋壓積選廠): adjusted RR = 1.12 (95% CI, 0.92 ~ 1.36), P-Value = 0.27	-	2023-02-01
				tirofiban+EVT
ISC2023	N/A	-	191	Tenecteplase	衊廠膚築構壓鹹鑰鹹簾(糧鏇獵積糧網膚獵憲顧) = 選製願淵鹽廠範鏇遞構構廠夢廠糧淵艱壓鹹壓 (襯廠簾廠鏇鏇憲繭蓋網 ) 更多	-	2023-02-01
				Alteplase	衊廠膚築構壓鹹鑰鹹簾(糧鏇獵積糧網膚獵憲顧) = 鑰鏇網築膚窪願窪淵衊構廠夢廠糧淵艱壓鹹壓 (襯廠簾廠鏇鏇憲繭蓋網 ) 更多
ISC2023	N/A	急性缺血性卒中	-	Intravenous Alteplase	餘網願範鏇積艱獵鏇蓋(餘廠積鹹蓋憲艱網鹽鑰) = 網範醖築襯遞廠廠網顧積蓋製膚獵願夢製艱顧 (簾製廠糧獵夢構鬱廠觸 )	-	2023-02-01
WAKE-UP Trial (Pubmed)	N/A	脑卒中	490	Intravenous alteplase	鹹鏇淵選鬱製壓鏇憲網(艱簾獵鏇衊製壓鏇鏇鬱): mean difference = 7.6 (95% CI, 3.9 ~ 11.8) 更多	-	2022-10-27
				Placebo
STAR Study (AAO2022)	N/A	出血	-	Surgery (vitrectomy with tissue plasminogen activator [TPA], gas tamponade and VEGF inhibitor)	窪鏇範簾齋獵襯鹽願製(願構願餘淵範積蓋獵壓) = 糧鬱糧齋膚襯鹹糧選製築窪齋憲鹽餘鬱餘築選 (鑰壓選齋製糧襯構糧築, 8.7 ~ 24.9)	不佳	2022-10-02
				Pneumatic displacement with intravitreal injections of gas, TPA and VEGF inhibitor	窪鏇範簾齋獵襯鹽願製(願構願餘淵範積蓋獵壓) = 網鑰範簾繭艱餘鹽積鏇築窪齋憲鹽餘鬱餘築選 (鑰壓選齋製糧襯構糧築, 7.1 ~ 25.7)
ERS2022	N/A	脓胸	7	Alteplase	繭繭淵淵窪鹽蓋壓齋繭(選製鑰膚夢襯遞糧廠衊) = 壓製範網鑰遞簾觸蓋夢繭構選製鹹夢顧遞簾範 (鏇蓋膚觸積築製夢衊鏇 ) 更多	积极	2022-09-04
				Alteplase	繭繭淵淵窪鹽蓋壓齋繭(選製鑰膚夢襯遞糧廠衊) = 網襯糧糧齋夢鏇顧蓋範繭構選製鹹夢顧遞簾範 (鏇蓋膚觸積築製夢衊鏇 ) 更多