Potential Combination Topical Therapy of Acne Vulgaris: a Randomized Controlled Trial Comparing Efficacy of DAP/FLU Micro-emulsion vs. Standard Therapy of Adapalene.

The investigators propose a randomized, double-blind control trial study to evaluate the efficacy and safety of the optimized topical combination ME of the investigated drugs in the treatment of acne vulgaris containing DAP-FLU in comparison with standard therapy of Adapalene at Mansoura University Dermatology and Andrology Outpatient Clinic.

开始日期2023-06-05

申办/合作机构

Mansoura University

NCT04597099 / Recruiting早期临床1期IIT

Ability of Androgen-receptor Blockade to Normalize Progesterone-induced Augmentation of Gonadotropin Secretion in PCOS (CRM010)

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

开始日期2022-10-26

申办/合作机构

University of Virginia

[+1]

NCT05050084 / Recruiting临床3期IIT

Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)

This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.

开始日期2021-11-03

申办/合作机构

NRG Oncology

[+1]

100 项与氟他胺相关的临床结果

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100 项与氟他胺相关的转化医学

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100 项与氟他胺相关的专利（医药）

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3,373

项与氟他胺相关的文献（医药）

2024-03-01·Phytomedicine : international journal of phytotherapy and phytopharmacology

Forsythiaside A attenuates mastitis via PINK1/Parkin-mediated mitophagy

Article

作者: Zhang, Huaqiang ; Gao, Yingkui ; Wen, Haojie ; Wang, Xuebing ; Hao, Zhonghua ; Liu, Jingjing ; Tong, Chao ; Zhou, Guangwei ; Su, Qing ; Yang, Xu

BACKGROUND:

Bovine mastitis is the most common animal production disease in the global dairy industry, which affects the health of dairy cows. When bovine mastitis occurs, the mitochondrial metabolism of breast tissue increases, and the relationship between inflammation and mitophagy has become a hot topic for many scholars. The abuse of antibiotics leads to the increase of resistance to bovine mastitis. FTA is one of the main effective components of Forsythia suspensa, which has anti-inflammatory, anti-infection, anti-oxidation and anti-virus pharmacological effects, and has broad application prospects in the prevention and treatment of bovine mastitis. However, the relationship between the anti-inflammatory effects of FTA and mitophagy is still unclear.

PURPOSE:

This study mainly explores the anti-inflammatory effect of FTA in bovine mastitis and the relationship between mitophagy.

METHODS:

MAC-T cells and wild-type mice were used to simulate the in vitro and in vivo response of mastitis. After the pretreatment with FTA, CsA inhibitors and siPINK1 were used to interfere with mitophagy, and the mitochondrial function impairment and the expression of inflammatory factors were detected.

RESULTS:

It was found that pre-treatment with FTA significantly reduced LPS induced inflammatory response and mitochondrial damage, while promoting the expression of mitophagy related factors. However, after inhibiting mitophagy, the anti-inflammatory effect of FTA was inhibited.

CONCLUSION:

This study is the first to suggest the relationship between the anti-inflammatory effect of FTA and mitophagy. PINK1/Parkin-mediated mitophagy is one of the ways that FTA protects MAC-T cells from LPS-induced inflammatory damage.

2024-05-01·Chinese journal of integrative medicine

Absorbed Bioactive Compounds Replicate Guanxin II-Induced Endothelium-Associated in/ex vivo Vasodilation

Article

作者: Huang, Yun-Ke ; Yu, Ai-Ling ; Chen, Ken ; Zhao, Qiu-Long ; Huang, Xi ; Huang, Wen-Ya ; Liu, Hao ; Xu, Min ; Li, Lan ; Su, Meng-Qing

OBJECTIVE:

To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals.

METHODS:

The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H₂O₂, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts.

RESULTS:

PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01).

CONCLUSION:

This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine.

2024-02-01·The Science of the total environment

ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase

Article

作者: Subbaroyan, Ajay ; Ravichandran, Janani ; Sahoo, Ajaya Kumar ; Chivukula, Nikhil ; Dhanakoti, Gokul Balaji ; Ramesh, Kundhanathan ; Samal, Areejit

Vitiligo is a complex disease wherein the environmental factors, in conjunction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. To address this knowledge gap, we present the first comprehensive knowledgebase of vitiligo-triggering chemicals namely, Vitiligo-linked Chemical Exposome Knowledgebase (ViCEKb). ViCEKb involves an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardizes various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Notably, we observed that ViCEKb chemicals are present in a variety of consumer products. For instance, Propyl gallate is present as a fragrance substance in various household products, and Flutamide is used in medication to treat prostate cancer. These two chemicals have the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Furthermore, an extensive cheminformatics-based investigation revealed that ViCEKb chemical space is structurally diverse and comprises unique chemical scaffolds in comparison with skin specific regulatory lists. For example, Neomycin and 2,3,5-Triglycidyl-4-aminophenol have unique chemical scaffolds and the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Finally, a transcriptomics-based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at: https://cb.imsc.res.in/vicekb.

项与氟他胺相关的新闻（医药）

2024-06-20

·PRNewswire

Polycystic Ovarian Syndrome Market to Advance at Moderate CAGR During the Study Period (2020-2034) | DelveInsight

According to DelveInsight's estimates, the increasing prevalence of diabetes, obesity, hormonal disorders, socioeconomic factors, changes in sedentary lifestyle, and growing consumption of unhealthy diets among women, is expected to fuel the polycystic ovary syndrome market. LAS VEGAS, June 20, 2024 /PRNewswire/ -- DelveInsight's Polycystic Ovarian Syndrome Market Insights report includes a comprehensive understanding of current treatment practices, polycystic ovarian syndrome emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Polycystic Ovarian Syndrome Market Report According to DelveInsight's analysis, the market size for polycystic ovarian syndrome is expected to grow significantly by 2034. According to the data provided by the Centers for Disease Control and Prevention (CDC), PCOS is one of the most common causes of female infertility, affecting 6% to 12% of US women of reproductive age. According to the data published by NHS, PCOS is thought to be very common, affecting about 1 in every 10 women in the UK. Leading polycystic ovarian syndrome companies such as Spruce Biosciences, and others are developing novel polycystic ovarian syndrome drugs that can be available in the polycystic ovarian syndrome market in the coming years. The promising polycystic ovarian syndrome therapies in the pipeline include Tildacerfont, among others. Discover which therapies are expected to grab the major polycystic ovarian syndrome market share @ Polycystic Ovarian Syndrome Market Report Polycystic Ovarian Syndrome Overview Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women, presenting a variety of signs, symptoms, and phenotypes. These can include reproductive, endocrine, and metabolic changes. PCOS is marked by dysfunction of the hypothalamic–pituitary–ovary axis and anovulation. Unlike other ovulatory failures characterized by inadequate ovarian follicle growth or suppressed gonadotropin secretion, PCOS usually involves androgen excess and subtle changes in serum levels of gonadotropins and estrogens that routine tests may not detect. The exact cause of PCOS remains unclear, but many women with the condition exhibit insulin resistance. Elevated insulin levels can lead to increased androgen production. Obesity can also raise insulin levels, exacerbating PCOS symptoms. PCOS often runs in families. Symptoms of PCOS may include missed or irregular periods, very light periods, enlarged ovaries or those with many cysts, excessive body hair (hirsutism) on the chest, stomach, and back, weight gain, particularly around the abdomen, acne or oily skin, and infertility. Polycystic Ovarian Syndrome Epidemiology Segmentation The polycystic ovarian syndrome epidemiology section provides insights into the historical and current polycystic ovarian syndrome patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The polycystic ovarian syndrome market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Prevalent Cases of Polycystic Ovarian Syndrome Diagnosed Prevalent cases of Polycystic Ovarian Syndrome Treatable Cases of Polycystic Ovarian Syndrome Polycystic Ovarian Syndrome Treatment Market The primary goal of treating polycystic ovarian syndrome is to manage symptoms and lower the risk of long-term complications. Presently, most treatments target the patient's main concern. The focus of treatment is on alleviating symptoms of hyperandrogenism, regulating menstrual cycles, and facilitating conception. Maintaining a healthy weight by following a balanced diet and engaging in regular exercise can enhance insulin sensitivity and help regulate menstrual cycles in individuals with PCOS who are overweight or obese. Incorporating complex carbohydrates, lean proteins, and plenty of vegetables into the diet can be advantageous. Some women with PCOS might find a low-carbohydrate or low-glycemic index diet particularly beneficial. Physical activity also aids in improving insulin resistance and managing weight. Spironolactone and flutamide can help decrease excess hair growth and acne by inhibiting the effects of male hormones (androgens). While Metformin is not approved for PCOS treatment in the UK, it can be prescribed "off-label" due to its benefits for many women with PCOS who have insulin resistance. Metformin can aid in improving fertility, regulating menstrual cycles, and lowering miscarriage risks. Additionally, it offers long-term health benefits like reducing high cholesterol levels and decreasing the risk of heart disease. To know more about polycystic ovarian syndrome treatment guidelines, visit @ Polycystic Ovarian Syndrome Management Polycystic Ovarian Syndrome Pipeline Therapies and Key Companies The pipeline for PCOS is bleak with only a few companies working diligently. Of all the major market players, Spruce Biosciences is developing Tildacerfont. Tildacerfont is a CRF1 receptor antagonist developed to potentially provide significantly better disease management and reduce steroid use in patients with classic congenital adrenal hyperplasia and other conditions with elevated adrenocorticotropic hormone (ACTH) levels. It works by binding to CRF1 receptors in the pituitary gland, thereby inhibiting the overproduction of ACTH and reducing the production of adrenal androgens like androstenedione, a precursor to testosterone. Tildacerfont is typically well-tolerated in both healthy individuals and those with rare endocrine disorders. Spruce is carrying out the P.O.W.E.R. study, a randomized, placebo-controlled, dose-escalation trial to assess the safety and efficacy of tildacerfont titrated to 200 mg once daily compared to a placebo over 12 weeks in subjects with PCOS and elevated adrenal androgens, measured by baseline dehydroepiandrosterone sulfate (DHEAS) levels. PCOS is a common hormonal disorder in women of reproductive age, characterized by hirsutism, irregular menstrual cycles, infertility, and ovarian cysts. If approved, Tildacerfont could be beneficial for women with a rare form of PCOS resulting from hyperresponsiveness to adrenal androgens. Discover more about polycystic ovarian syndrome drugs in development @ Polycystic Ovarian Syndrome Clinical Trials Polycystic Ovarian Syndrome Market Dynamics The dynamics of the polycystic ovarian syndrome market are expected to change in the coming years. Rising awareness about PCOS and its associated complications, such as infertility, metabolic syndrome, and diabetes, has heightened the demand for effective diagnostic and treatment options. Advances in medical technology and diagnostics have also played a significant role, with improved imaging techniques and blood tests enabling earlier and more accurate detection of PCOS. Additionally, the growing emphasis on personalized medicine and tailored treatment regimens is fueling the market, as healthcare providers seek to offer more specific and effective therapies for managing PCOS symptoms. Furthermore, potential therapies are being investigated for the treatment of polycystic ovarian syndrome, and it is safe to predict that the treatment space will significantly impact the polycystic ovarian syndrome market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the polycystic ovarian syndrome market in the 7MM. However several factors may impede the growth of the polycystic ovarian syndrome market. One of the major challenges is the lack of standardized diagnostic criteria, which can lead to underdiagnosis or misdiagnosis, thus limiting the potential market size. Treatment adherence is another concern, as the chronic nature of PCOS often requires long-term management strategies that patients may find difficult to maintain. Furthermore, there is a need for more comprehensive and effective treatment options; current therapies primarily focus on symptom management rather than addressing the underlying causes of PCOS. Moreover, polycystic ovarian syndrome treatment poses a significant economic burden and disrupts patients' overall well-being and QOL. Furthermore, the polycystic ovarian syndrome market growth may be offset by failures and discontinuation of emerging therapies, unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact the polycystic ovarian syndrome market growth. Scope of the Polycystic Ovarian Syndrome Market Report Therapeutic Assessment: Polycystic Ovarian Syndrome current marketed and emerging therapies Polycystic Ovarian Syndrome Market Dynamics: Key Market Forecast Assumptions of Emerging Polycystic Ovarian Syndrome Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Polycystic Ovarian Syndrome Market Access and Reimbursement Download the report to understand which factors are driving polycystic ovarian syndrome market trends @ Polycystic Ovarian Syndrome Market Trends Table of Contents Related Reports Polycystic Ovarian Syndrome Pipeline Polycystic Ovarian Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key polycystic ovarian syndrome companies, including Spruce Biosciences, Zydus Therapeutics, AbbVie, among others. Polycystic Ovarian Syndrome Epidemiology Forecast Polycystic Ovarian Syndrome Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted polycystic ovarian syndrome epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Type 2 Diabetes Pipeline Type 2 Diabetes Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key type 2 diabetes companies, including Sanofi, Eli Lilly and Company, Novartis, among others. Type 2 Diabetes Market Type 2 Diabetes Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key type 2 diabetes companies, including Eli Lilly and Company, Regor Pharmaceuticals Inc., AstraZeneca, Eccogene, Pfizer, Sciwind Biosciences USA Co., Ltd., MediciNova, Sparrow Pharmaceuticals, HighTide Biopharma Pty Ltd, Novo Nordisk A/S, Biomea Fusion Inc., Altimmune, Inc., Novartis, Amgen, Neuraly, Inc., Carmot Therapeutics, Inc., Inventiva Pharma, Inversago Pharma Inc, Applied Therapeutics, Inc. , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

上市批准

2024-02-05

·BioSpace

Goserelin Dosing Options Included in the National Comprehensive Cancer Network® (NCCN) Breast Cancer Guidelines

DEERFIELD, Ill.--(BUSINESS WIRE)-- TerSera Therapeutics LLC announced today that The National Comprehensive Cancer Network® (NCCN) Breast Cancer Panel included both goserelin 3.6 mg every 4 weeks and goserelin 10.8 mg every 12 weeks, as methods for ovarian function suppression in Version 1.2024 of the Breast Guidelines revised as of January 25, 2024.1 "In addition to the 3.6 mg monthly dose, I am pleased to see that NCCN recognizes the role of goserelin 10.8 mg every 12 weeks as an option for premenopausal women with hormone receptor positive (HR+) breast cancer, ” said Virginia Kaklamani, MD, Professor of Medicine in the Division of Hematology and Medical Oncology at the University of Texas Health Sciences Center San Antonio and leader of the breast cancer program at the Mays Cancer Center, home to UT Health San Antonio MD Anderson. The inclusion of goserelin 10.8 mg every 12 weeks in the breast cancer guidelines as a method for ovarian function suppression is a category 2A recommendation. Multiple international studies have evaluated the safety and efficacy of goserelin 10.8 mg every 12 weeks for ovarian function suppression in premenopausal patients with HR+ breast cancer.2-5 In the United States, ZOLADEX® (goserelin implant) 3.6 mg is the only dosage form approved for use in breast cancer. ZOLADEX 10.8 mg is not approved by FDA for breast cancer. Please see the full Prescribing Information for ZOLADEX 3.6 mg and ZOLADEX 10.8 mg and additional Important Safety Information below. Worldwide, ZOLADEX 3.6 mg is approved for use in breast cancer in 125 countries. Additionally, ZOLADEX 10.8 mg is approved for use in breast cancer in over 60 countries, with multiple additional regulatory reviews underway. This is the third update to NCCN guidelines regarding goserelin over the past few months related to head and neck cancers (V1.2024), ovarian cancer (V1.2024), and breast cancer (V1.2024). About ZOLADEX® (goserelin implant) ZOLADEX is an injectable luteinizing hormone-releasing hormone agonist (LHRHa) used to treat prostate cancer, breast cancer, and certain benign gynecological disorders. First approved in the U.S. in 1989, ZOLADEX is available as a 3.6 mg implant dosed every 28 days or as a 10.8 mg implant dosed every 12 weeks.6,7 U.S. INDICATIONS ZOLADEX 3.6 mg and ZOLADEX 10.8 mg are indicated for: Management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate in combination with flutamide. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy. Palliative treatment of advanced carcinoma of the prostate. ZOLADEX 3.6 mg is also indicated for: Management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy. Experience with ZOLADEX for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months. Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding. Palliative treatment of advanced breast cancer in pre- and perimenopausal women. IMPORTANT SAFETY INFORMATION Anaphylactic reactions to ZOLADEX have been reported in the medical literature. ZOLADEX is contraindicated in patients with a known hypersensitivity to GnRH, GnRH agonist analogues, or any of the components in ZOLADEX. ZOLADEX is contraindicated during pregnancy unless used for palliative treatment of advanced breast cancer. ZOLADEX can cause fetal harm when administered to a pregnant woman. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormonal changes that occur with ZOLADEX treatment. ZOLADEX should not be given to women with undiagnosed abnormal vaginal bleeding. Pregnancy must be excluded for use in benign gynecological conditions. Women should be advised against becoming pregnant while taking ZOLADEX. Effective nonhormonal contraception must be used by all premenopausal women during ZOLADEX therapy and for 12 weeks following discontinuation of therapy. Transient worsening of tumor symptoms, or the occurrence of additional signs and symptoms of breast cancer, may occasionally develop during the first few weeks of treatment. Some patients may experience a temporary increase in bone pain. Monitor patients at risk for complications of tumor flare. Hyperglycemia and an increased risk of developing diabetes or worsening of glycemic control in patients with diabetes have been reported in men receiving GnRH agonists like ZOLADEX. Monitor blood glucose levels and glycosylated hemoglobin (HbA1c) periodically and manage according to current clinical practice. Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists like ZOLADEX in men. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice. Hypercalcemia has been reported in some breast cancer patients with bone metastases after starting treatment with ZOLADEX. If hypercalcemia does occur, appropriate treatment measures should be initiated. Hypersensitivity, antibody formation and acute anaphylactic reactions have been reported with GnRH agonist analogues. ZOLADEX may cause an increase in cervical resistance. Therefore, caution is recommended when dilating the cervix for endometrial ablation. GnRH agonists may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes. Injection site injury and vascular injury including pain, hematoma, hemorrhage and hemorrhagic shock, requiring blood transfusions and surgical intervention, have been reported with ZOLADEX. Extra care should be taken when administering ZOLADEX to patients with low BMI and/or to patients receiving full dose anticoagulation. Depression may occur or worsen in women receiving GnRH agonists. Treatment with ZOLADEX may be associated with a reduction in bone mineral density over the course of treatment. Data suggest a possibility of partial reversibility. In women, current available data suggest that recovery of bone loss occurs on cessation of therapy in the majority of patients. In women, the most frequently reported adverse reactions were related to hypoestrogenism. The adverse reaction pro similar for women treated for breast cancer, dysfunctional uterine bleeding, and endometriosis. The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometriosis were: hot flashes (96%), vaginitis (75%), headache (75%), decreased libido (61%), emotional lability (60%), depression (54%), sweating (45%), acne (42%), breast atrophy (33%), seborrhea (26%), and peripheral edema (21%). The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometrial thinning were: vasodilation/hot flashes (57%), headache (32%), sweating (16%), and abdominal pain (11%). The most commonly reported adverse reactions with ZOLADEX in breast cancer clinical trials were hot flashes (70%), decreased libido (47.7%), tumor flare (23%), nausea (11%), edema (5%), and malaise/fatigue/lethargy (5%). Injection site reactions were reported in less than 1% of patients. For ZOLADEX 3.6 mg: Hot flashes (62%), sexual dysfunction (21%), decreased erections (18%), lower urinary tract symptoms (13%), lethargy (8%), pain (worsened in the first 30 days) (8%), edema (7%), upper respiratory infection (7%), rash (6%), and sweating (6%). For ZOLADEX 10.8 mg: Hot flashes (64%), pain (general) (14%), gynecomastia (8%), pelvic pain (6%), and bone pain (6%). In the locally advanced carcinoma of the prostate clinical trial, additional adverse event data were collected for the combination therapy with radiation group during both the hormonal treatment and hormonal treatment plus radiation phases of this study. Adverse experiences (incidence >5%) in both phases of this study were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%). Treatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone. Please see Full Prescribing Information for ZOLADEX 3.6 mg and ZOLADEX 10.8 mg. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit fda.gov/medwatch or call 1-800-FDA-1088. You can also contact TerSera Therapeutics at 1-844-334-4035 or medicalInformation@tersera.com. About TerSera Therapeutics TerSera Therapeutics is a biopharmaceutical company with a focus in oncology, acute care, and non-opioid pain management. Founded in 2016, TerSera is building new cornerstones of care through its portfolio of unique therapeutics, amplifying their ability to deliver meaningful outcomes for patients. For more information about TerSera Therapeutics, please visit tersera.com. References NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Version 1.2024. © National Comprehensive Cancer Network, Inc 2024. All rights reserved. [Accessed January 29, 2024]. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Noguchi S, Kim HJ, Jesena A, et al. Phase 3, open-label, randomized study comparing 3-monthly with monthly goserelin in pre-menopausal women with estrogen receptor-positive advanced breast cancer. Breast Cancer. 2016; 23:771-779. Masuda N, Iwata H. Rai Y, et al. Monthly versus 3-monthly goserelin acetate treatment in pre-menopausal patients with estrogen receptor-positive early breast cancer. Breast Cancer Res Treat. 2011; 126:443-451. El Zawawy SF, Khedr G. 209P Efficacy and feasibility of long acting every three months goserelin for premenopausal breast cancer patients during COVID pandemic. Annals of Oncology. 2022;33: S631. Wu H, Bian L, Xie J, et al. 111P Goserelin 3 monthly depot is noninferior to goserelin monthly depot in the treatment of breast cancer: A real-world evidence study. ESMO Open. 2023;8(1):101335. ZOLADEX (goserelin implant) 3.6 mg prescribing information. TerSera Therapeutics LLC. ZOLADEX (goserelin implant) 10.8 mg prescribing information. TerSera Therapeutics LLC. ZOLADEX® is a registered trademark of AstraZeneca or its affiliates and is used herein under license. ©2024 TerSera Therapeutics LLC. All rights reserved.

临床结果上市批准临床3期放射疗法

2023-10-25

·药渡Daily

前列腺保卫战，AR抑制剂国产替代正当时

前列腺癌作为男性的“专属”癌症，在我国已经成为了男性发病率第六的恶性肿瘤，多发于65岁以上老人，且至今发病率依然在攀升，也因此成就了上百亿美元的市场。雄激素受体（AR）在前列腺癌的发展有着重要的影响，因此AR也成为治疗前列腺癌的重要靶点，AR抑制剂成为治疗前列腺癌的重要手段之一。随着国产大军的加入，国内AR抑制剂市场再度涌动，且愈加剧烈。半壁江山随着安斯泰来恩扎卢胺用于治疗转移性激素敏感性前列腺癌（mHSPC）新适应症获CDE受理，使得这款畅销药在中国即将集齐前列腺癌三大适应症（mHSPC、mCRPC、nmCRPC）“大满贯”。在美国市场，恩扎卢胺早已在2019年12月获批扩展适应症，成为全球第一款可治疗三种不同形态晚期前列腺癌（mHSPC、mCRPC、nmCRPC）的口服药物。2019年，恩扎卢胺在全球前列腺癌药物市场份额中的占比已达到33.9%，2022年更是创下46亿美元的销售额，成为前列腺癌治疗领域名副其实的“药王”。恩扎卢胺的实力超群，主要归功于其作用靶点——雄激素受体（AR）。来源：安斯泰来官网前列腺癌作为男性新发及死亡最高的瘤种之一，新发患者正在逐年增加。近年来，我国前列腺癌发病率已呈现快速上升趋势，且患者在就诊时大多数已处于晚期，5年生存率显著低于发达国家。前列腺癌属于多阶段进行性疾病，其多个演变阶段具有不同的分子特征、药物反应和耐药机制，因此需在不同的演变阶段更换不同的治疗方案。具体来看，前列腺癌可分为几种类型：局限性前列腺癌、转移性激素敏感性前列腺癌（mHSPC）、非转移性去势抵抗性前列腺癌（nmCRPC）和转移性去势抵抗性前列腺癌（mCRPC）。其中，mCRPC是前列腺癌的主要致死因素，进展至mCRPC者平均中位生存时间少于2年。目前，市场上治疗前列腺癌的药物超过10种，其中以雄激素剥夺治疗（ADT）和雄激素受体（AR）治疗占据主要市场份额。在未来10年，前列腺癌治疗领域AR抑制剂仍然将会是市场上销售额最大的品种。来源：参考资料2由于前列腺癌具有雄激素依赖性，因此通过控制雄激素能达到治疗前列腺癌的目的。雄激素受体（AR）是一种类固醇受体，作为调节基因表达的DNA结合转录因子，通过结合雄激素，包括睾酮和二氢睾酮在细胞质中，然后易位到细胞核，从而调节一系列基因的转录。AR抑制剂的作用机制，就是内源性阻断雄性激素与AR的结合，从而抑制AR信号通路的正常激活，阻断雄性激素和AR的结合，让雄性激素无法发挥其生物学效应，进而影响前列腺癌细胞的生长与增殖，达到治疗前列腺癌的目的。在前列腺癌的治疗中，AR抑制剂是个十分重要的治疗手段，可贯穿早期内分泌治疗至去势抵抗性前列腺癌（CRPC）。基于AR抑制剂在前列腺癌治疗方面出色的疗效，AR抑制剂在前列腺癌药物占比达56%，随着二代产品市场份额增加及联用疗法的探索，到2029年占比有望达57.8%，这其中恩扎卢胺依旧雄风不减。独领风骚截至目前，全球范围内已上市的治疗前列腺癌的AR抑制剂有7款，分别为第一代AR抑制剂氟他胺、尼鲁米特、比卡鲁胺和第二代AR抑制剂恩扎卢胺、阿帕鲁胺、达洛鲁胺和瑞维鲁胺，其中瑞维鲁胺为国产原研药物。来源：药渡数据以比卡鲁胺为代表的一代非甾体类AR抑制剂曾经是治疗前列腺癌的一线用药，但是由于对晚期前列腺癌疗效不显著，并有可能激活促进肿瘤的生长，逐渐退出了历史舞台，而以恩扎卢胺为首的二代AR抑制剂逐渐成为了主流治疗药物。2021年，美国市场二代AR抑制剂已全面替代一代药物，其中恩扎卢胺在美国前列腺癌药物市场占比达38%。安斯泰来的恩扎卢胺软胶囊于2012年在美国获批上市，用于治疗化疗失败后的mCRPC，此后还获批了未经化疗的mCRPC、nmCRPC和mHSPC等适应症，贯穿前列腺癌治疗的多个阶段。2021年、2022年全球销售额分别高达41亿美元、46亿美元。在国内市场，前列腺癌诊疗中仍以第一代AR药物为主。根据药渡数据，2022年，比卡鲁胺为AR抑制剂中销售额最高的产品，总销售规模达8.3亿元，由于纳入集采，同比下降44.07%。其中阿斯利康市占率46.66%、朝晖药业18.28%、振东制药17.58%、海正药业15.14%等；氟他胺总销售额2930万元，由天士力和复旦复华瓜分。国内2022年比卡鲁胺市场竞争格局来源：药渡数据恩扎卢胺等二代产品由于上市时间较晚，目前市场份额占比较低，但二代AR抑制剂进入医保后放量可期，且具备广阔的一代AR药物迭代的市场空间。根据药渡数据，2022年，恩扎卢胺总销售规模3.1亿元，原研厂家安斯泰来和首仿豪森药业瓜分市场，市占率分别为95.28%、4.72%；阿帕鲁胺总销售规模2.34亿元，仍由原研厂家杨森独占。国内2022年恩扎卢胺市场竞争格局来源：药渡数据在二代AR抑制剂仍由外资企业把持的局面下，我们欣慰地看到，国内药企正在不断奋进中，并且已经取得了阶段性胜利。谁与争锋恒瑞医药的瑞维鲁胺（艾瑞恩）是中国首个自主研发的第二代AR抑制剂，于2022年6月获批高瘤负荷的转移性激素敏感性前列腺癌适应症。根据CHART研究结果表明，与标准治疗相比，瑞维鲁胺联合雄激素剥夺疗法（ADT）可显著延长患者的总生存期，并显著降低患者死亡和疾病进展风险分别达42%和54%。在Fast-follow的策略下，恒瑞医药的速度果真无人能比。来源：恒瑞医药官网HC-1119国产在研管线中，海创药业研发的HC-1119（氘恩扎鲁胺）已提交了新药上市申请，并于今年3月获受理。HC-1119是恩扎卢胺的氘代化合物，海创药业2023年半年报显示，HC-1119相比恩扎卢胺的优势在于其开发策略是针对二线、三线的mCRPC患者，临床使用剂量仅有恩扎卢胺的一半，并不影响有效性，安全性和病人依从性大大提高，有成为Best-in-class（同类最佳）品种的潜力。普克鲁胺开拓药业的普克鲁胺的前列腺癌适应症也处于临床III期。普克鲁胺是个悲情角色。在新冠疫情初期，普克鲁胺被用于开发成新冠特效药，并且在巴西的临床试验收获了惊艳的临床数据。然而，这一数据遭到了美国FDA的质疑，不得不在美国本土再次开展试验。结果，2021年12月，开拓药业公布III期临床中期试验未达到统计学显著性。尽管后来再次验证普克鲁胺可有效降低轻、中症患者住院率及死亡率，但无奈市场风向已转变，普克鲁胺也逐渐销声匿迹。而作为前列腺癌适应症的普克鲁胺，正在国内开展联合阿比特龙一线治疗mCRPC多中心、随机、双盲III期临床试验，预计2023年下半年或2024年上半年完成试验。此外，普克鲁胺治疗恩扎卢胺或阿比特龙耐药的mCRPC患者的二线疗法在美国开展的II期临床试验也接近尾声。从市场空间看，前列腺癌治疗的市场天花板较高，不同的治疗路径也使得前列腺癌治疗药物市场的容量加剧攀升。以AR为靶点的药物研发是长期以来倍受关注的热点，也持续推动了多种药物进入临床应用。AR抑制剂市场布局企业较多，目前全球范围内还有多款AR抑制剂处于临床研究阶段，随着研发进程加快，AR抑制剂种类将日渐丰富，与此同时，AR抑制剂市场竞争也将加剧。根据药渡数据，全球范围内在研 AR 抑制剂相关项目已超 105个，国内除上述药企布局外，还包括普恒医药、正大天晴等也有布局。部分AR抑制剂相关研发管线来源：药渡数据整理结语随着前列腺癌患者增加，前列腺癌药物仍将保持增长态势，AR抑制剂作为主流治疗要求，未来亦具有广阔发展空间。此外AR靶点潜在适应症广泛，目前已开展临床试验的适应症涵盖乳腺癌、脱发、避孕、女性激素依赖性疾病等领域，为药企们提供了丰富的研发思路。目前国产替代虽然已由恒瑞医药开启，但仍有较大替代空间，未来可期。后续发展如何，药渡还将持续关注。参考资料1、各大药企官网、公告等2、《恒瑞、开拓、海创围猎前列腺癌「药王」》，赛柏蓝，2023-10-093、《前列腺癌为世界最常见恶性肿瘤：全球AR抑制剂市场超 200亿美元》，财闻网，2023-07-13

临床研究临床终止

100 项与氟他胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00586	氟他胺	L02BB01	DB00499

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
前列腺癌	美国	Schering Corp.	1989-01-27

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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


NCT00450463 (Pubmed)	临床2期	去势抵抗性前列腺癌	64	Flutamide	餘蓋簾顧鹽艱鏇遞膚範(壓構繭鏇夢憲艱鏇顧醖) = The most common side effect > grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting 遞襯糧衊範鏇艱衊獵鹽 (製鏇廠壓鏇廠獵窪夢鑰 )	不佳	2023-05-03
				Flutamide+vaccine
NCT02918968 (CTgov)	临床4期	转移性去势抵抗性前列腺癌	206	Androgen deprivation therapy+Enzalutamide+Flutamide (Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT)	遞築夢網餘鹽淵膚鹹簾(簾糧觸築衊範築鑰鑰憲) = 築構鏇壓醖淵窪夢廠糧築鹽鹹遞鏇壓鑰醖製願 (簾淵築蓋網窪鹽壓繭網, 淵夢蓋願築積顧獵網鑰 ~ 觸顧淵壓齋餘醖鏇範鏇) 更多	-	2021-05-21
				Androgen deprivation therapy+Enzalutamide+Flutamide (Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT)	遞築夢網餘鹽淵膚鹹簾(簾糧觸築衊範築鑰鑰憲) = 膚築壓遞積糧鏇願網齋築鹽鹹遞鏇壓鑰醖製願 (簾淵築蓋網窪鹽壓繭網, 窪簾簾遞壓夢鏇糧膚願 ~ 鹽鏇壓齋窪壓繭艱膚憲) 更多
NCT00611923 (CTgov)	临床4期	经前焦虑症 \| 经前综合征	115	lactose (Placebo)	齋選壓鬱衊壓艱憲築糧(廠鏇鹹淵簾餘鑰積繭膚) = 製遞淵醖餘築廠壓鹹鏇襯獵積糧夢繭糧鏇鹽壓 (選餘鹽窪繭餘簾遞艱願, 夢範餘壓衊壓憲鏇膚膚 ~ 憲鹹膚衊鏇淵製選壓鹹) 更多	-	2019-11-19
				Flutamide (Flutamide)	齋選壓鬱衊壓艱憲築糧(廠鏇鹹淵簾餘鑰積繭膚) = 膚顧蓋範糧願積鹽網糧襯獵積糧夢繭糧鏇鹽壓 (選餘鹽窪繭餘簾遞艱願, 選願觸構蓋顧鹹糧積範 ~ 鹽鑰鬱壓選簾觸鹽鑰鏇) 更多
ASN2019	N/A	多囊肾	-	Flutamide	淵構齋齋繭願鬱壓醖鹽(糧鏇憲憲鑰鹽鑰齋願餘) = 蓋觸窪壓蓋繭齋鹽鬱艱觸選襯範鏇憲獵衊鹽壓 (鹹鏇遞膚鏇鹽鏇鹽鹽糧 ) 更多	积极	2019-11-05
NCT01428193 (CTgov)	N/A	雄激素过多 \| 多囊卵巢综合征	4	Progesterone+Flutamide+estrace	製窪簾襯鏇簾範獵鬱鑰(範網繭艱積廠鹹獵窪夢) = 繭糧鏇積獵顧鑰窪顧鏇廠鹽夢構鹹網餘夢衊餘 (獵網簾醖糧築網觸膚顧, 醖構鏇鑰鹹壓壓網餘壓 ~ 構蓋襯簾窪觸積醖鏇蓋) 更多	-	2018-06-04
NCT00223665 (CTgov)	临床2期	局限性前列腺癌 \| 非转移性前列腺癌	102	Flutamide+Leuprolide Acetate	憲遞衊夢積糧壓網顧醖(獵觸艱鑰壓選繭願糧廠) = 網獵蓋遞醖選觸艱齋鏇襯鏇願淵鹽壓選觸壓膚 (獵艱願衊廠鑰簾窪鑰衊, 淵憲鑰艱鏇襯鑰鬱艱襯 ~ 簾齋獵廠築鏇壓鹹範壓) 更多	-	2018-05-14
NCT00005044 (CTgov)	临床3期	前列腺癌	1,579	LHRH agonist+Casodex+Eulexin (TAS x 8 Weeks)	鑰鹽選鬱遞鹹積鏇鏇範(醖艱範夢鏇淵襯範網獵) = 夢淵築餘膚膚鑰積衊艱觸窪艱膚顧糧獵蓋蓋衊 (製鹽願鹽襯選齋願願範, 積遞壓範夢願艱窪積醖 ~ 醖鑰鹹製觸齋醖顧鏇憲) 更多	-	2017-10-31
				LHRH agonist+Casodex+Eulexin (TAS x 28 Weeks)	鑰鹽選鬱遞鹹積鏇鏇範(醖艱範夢鏇淵襯範網獵) = 壓願獵襯窪淵餘夢鬱觸觸窪艱膚顧糧獵蓋蓋衊 (製鹽願鹽襯選齋願願範, 繭遞築獵鹽築糧觸衊淵 ~ 齋餘夢選構齋夢夢鬱醖) 更多
NCT00528866 (RTOG 0621, CTgov)	临床2期	前列腺癌	80	3-dimensional conformal radiation therapy+Docetaxel+bicalutamide+flutamide	醖壓淵窪壓淵淵鑰選鏇(獵顧繭選襯鏇鏇簾憲築) = 鏇艱鹹窪鏇鑰鑰糧蓋憲膚築積壓鹹顧醖遞蓋製 (顧衊觸憲範遞範醖鑰鏇, 簾築積繭觸製願積範構 ~ 衊製淵鹽構獵壓餘夢繭) 更多	-	2017-06-06
ASCO_GU2016	N/A	转移性去势抵抗性前列腺癌二线	65	flutamide (Low risk group (0-2 risk factors present))	膚簾夢膚鹽製襯廠遞餘(鏇廠鬱鬱衊鹽齋襯遞構) = 製憲網淵選鹹齋衊齋願範鏇醖衊遞醖鹹選餘憲 (範壓膚構襯衊憲願醖顧 )	积极	2016-01-10
				flutamide (High risk group (3-4 risk factors present))	膚簾夢膚鹽製襯廠遞餘(鏇廠鬱鬱衊鹽齋襯遞構) = 艱獵夢選鹹醖鏇願鹽壓範鏇醖衊遞醖鹹選餘憲 (範壓膚構襯衊憲願醖顧 )
NCT00442689 (CTgov)	N/A	代谢综合征 \| 多囊卵巢综合征	97	ethinyl estradiol+drospirenone (Oral Contraceptive - 1)	範構鏇醖獵鬱艱積鏇衊(窪衊網繭憲窪顧築鬱壓) = 觸選願憲簾淵鹽繭製鏇網簾鏇廠膚築憲繭簾壓 (鏇顧蓋積觸製積蓋遞醖, 觸衊蓋壓窪夢膚鬱艱餘 ~ 鬱蓋築壓願鏇鹹夢觸艱) 更多	-	2014-06-06
				Flutamide - 2 (Flutamide - 2)	範構鏇醖獵鬱艱積鏇衊(窪衊網繭憲窪顧築鬱壓) = 積遞獵選憲築醖構夢構網簾鏇廠膚築憲繭簾壓 (鏇顧蓋積觸製積蓋遞醖, 醖構憲艱製窪衊顧廠憲 ~ 鏇鹽積衊憲襯範鏇構淵) 更多