Testosterone

▎药明康德内容团队编辑Lipocine今天公布其在研疗法LPCN 2401临床2期试验的积极结果。分析显示，LPCN 2401治疗使得肥胖或超重且患有至少一项体重相关共病患者，其身体的肌肉量（LM）显著增加并脂肪量（FM）显著减少。根据新闻稿，LPCN 2401具有潜力与胰高血糖素样肽1（GLP-1）类药物联合使用，或作为这类疗法停药后维持患者体重的单药疗法。这项多中心2期试验包括肥胖（BMI≥30）和超重（BMI≥27）且至少患有一种体重相关合并症（例如高血压、2型糖尿病、血脂异常）的受试者。受试者随机接受以下三种治疗之一，为期36周：（A）睾酮酯单药胶囊、（B）LPCN 2401，或（C）安慰剂。受试者在基线、第20周和第36周接受双能X射线吸收仪（DEXA）扫描，以测量其身体组成。在接受治疗选项B和C治疗的患者中，27名受试者被随机分配并完成基线和至少一次基线后DEXA分析。基线时，患者的平均BMI为36.0 kg/m2，平均年龄为52.4岁。分析显示，在36周时，与安慰剂相比，LPCN 2401治疗使得患者的LM增加4.4%，FM减少6.7%。研究人员早在第20周就观察到患者身体组成的显著改善。此外，LPCN 2401治疗同时降低患者的腹部脂肪（AF）达4.1%，并增加其骨矿物质含量（BMC）达2.8%。药物治疗对患者的体重没有影响，患者的脂肪减少被其无脂体重增加所抵消。总体而言。LPCN 2401治疗显著改善患者的身体组成，使得其脂肪量/肌肉量比率大幅下降。此外，与接受治疗选项A的患者相比，LPCN 2401导致的脂肪量减少更大。使用LPCN 2401后，患者的血压和糖化血红蛋白数值展现改善的趋势。▲LPCN 2401的疗效结果（图片来源：参考资料[1]）LPCN 2401耐受性良好，观察到的治疗引起的不良反应频率和严重程度与安慰剂相当。接受LPCN 2401治疗的受试者没有报告任何胃肠道或肌肉痉挛不良事件。LPCN 2401是一款口服药物，其专有配方结合了雄激素受体激动剂和抗氧化代谢调节剂α-生育酚。临床前和临床研究数据表明，LPCN 2401具备同时减少脂肪并增加肌肉的潜力。作为GLP-1类药物的潜在辅助疗法，LPCN 2401有望减轻停药后的体重反弹、改善肌肉质量下降、提升肌肉质量及功能。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Lipocine Announces Positive LPCN 2401 Clinical Results Showing Improved Body Composition in Participants with Obesity. Retrieved April 11, 2024 from https://www.prnewswire.com/news-releases/lipocine-announces-positive-lpcn-2401-clinical-results-showing-improved-body-composition-in-participants-with-obesity-302114311.html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。版权说明：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「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Data Published in Therapeutic Advances in Urology Demonstrates Up to 96% Efficacy in Helping Restore Testosterone Levels to Normal at Day 901* RALEIGH, N.C., April 11, 2024 /PRNewswire/ -- Marius Pharmaceuticals, a pharmaceutical company focused on developing innovative therapies for testosterone deficiency, today announced published results from MRS-TU-2019EXT, a six-month clinical trial of 139 men with low testosterone studying the safety and efficacy of its oral testosterone replacement therapy, KYZATREX® (testosterone undecanoate) CIII Capsules in adult men with conditions associated with a deficiency or absence of endogenous testosterone. The data, published in Therapeutic Advances in Urology, demonstrated that KYZATREX was up to 96% effective at Day 90 at restoring normal testosterone levels in adult men who have low or no testosterone levels due to certain medical conditions.1* *Per label, 88% of patients had low testosterone levels at Day 90 (worst-case scenario calculation, excluding Site 104). Based on patients who completed the study (n=127), 96% of patients achieved normal testosterone levels at Day 90.1 "The world is experiencing a crisis related to men's health, and we firmly believe that oral testosterone in the form of KYZATREX has the potential to be a critical part of the solution," said Shalin Shah, chief executive officer of Marius Pharmaceuticals. "Not only does the data demonstrate that KYZATREX is a safe and effective form of testosterone replacement therapy, but it also shows that KYZATREX is effective at decreasing the amount of sex hormone binding globulin (SHBG) and increasing the amount of free testosterone in the body. We believe combining the convenience of our oral delivery system with the testosterone-boosting benefits of testosterone undecanoate can be transformative for men suffering from testosterone deficiency and in helping to correct the substantial drop in testosterone levels among men in the United States over the past few decades." Select Results from MRS-TU-2019EXT MRS-TU-2019EXT was a 6-month, open-label study involving 139 hypogonadal men (median age of 50 years; range 22 to 66 years). The primary efficacy endpoint was the percentage of KYZATREX-treated patients with mean plasma total testosterone concentration (Cavg) over 24-hours within the normal range of 222-800 ng/dL on the final pharmacokinetic visit of the study at Day 90. KYZATREX demonstrated the following: Up to 96 Efficacy1 Per label, 88% of patients had low testosterone levels at Day 90 (worst-case scenario calculation, excluding Site 104). Based on patients who completed the study (n=127), 96% of patients achieved normal testosterone levels at Day 90. Safety Profile After 120 days of treatment, the change in 24-hour mean systolic blood pressure from baseline was 1.7 mmHg (95% CI, 0.3 to 3.1). After 190 days of treatment the blood pressure change appeared stable with a mean increase of 1.8 mmHg (95% CI, 0.3 to 3.2).1 Only one drug-related adverse event was observed in more than 2% of study participants: hypertension (2%).1 The article notes that, "The reported mean increase in systolic BP (blood pressure) is the lowest of the label-reported BP increases for the three FDA-approved oral TU (testosterone undecanoate) products."1 2x Increase in Free Testosterone1 Mean Free Testosterone levels increased from 7.0 ng/dL to 14.1 ng/dL after 90 days of treatment. Impact on FSH and LH While both FSH (follicle stimulating hormone) and LH (luteinizing hormone), which are critical for sperm production and male fertility, both decreased after 90 and 180 days of KYZATREX treatment, levels did not drop to zero at either of the two post-Baseline visits.1 The authors of the study were James S. Bernstein, PhD, and Om Dhingra, PhD, board director and scientific advisor to Marius Pharmaceuticals. Om Dhingra commented, "The excellent safety and efficacy data can be attributable to KYZATREX's innovative and elegant formulation. This formulation utilizes phytosterols as a first in a pharmaceutical product to help make safe and effective Oral Testosterone a reality. We have expanded the traditional framework, as well, when considering effects of SHBG and Free Testosterone, which potentially mark a new era in treatment focused on usable testosterone, not just total T. We look forward to this being the beginning of a broader research program to better understand and demonstrate real world benefits of testosterone as a metabolic hormone." Testosterone deficiency – or hypogonadism – is a chronic disease that affects about 30 percent of men aged 20 years and older.2 In a 24-year study, researchers noted a substantial age-independent decline in testosterone levels among men in the U.S. Since the study's inception in 1984, it was determined that men born in more recent years have lower testosterone levels than previous generations, with average levels declining by about 1% per year.3 Compounding the issue, it's been reported that only 5-10% of men with low testosterone are being treated with testosterone replacement therapy (TRT).4 Historically, TRT has been administered through injections, pellets and gels. KYZATREX is designed to utilize lymphatic absorption to bypass first-pass metabolism to drive uptake and prevent liver damage. KYZATREX is an immediate-release formulation with twice-daily dosing that, when administered every 12 hours, closely mimics the diurnal rhythm of endogenous testosterone, as demonstrated by the pharmacokinetic data in the study article.1 This published study is part of Marius Pharmaceuticals' comprehensive effort to develop innovative therapies for testosterone deficiency. To learn more about KYZATREX®, visit . To learn more about Marius Pharmaceuticals, visit . The full journal article can be found here. About KYZATREX® (testosterone undecanoate) KYZATREX is a proprietary softgel oral formulation absorbed primarily via the lymphatic system (meaning it is not toxic to the liver) indicated in adult males for conditions associated with a deficiency or absence of endogenous testosterone. The safety and efficacy of KYZATREX was demonstrated in a phase 3, multi-center, open-label, six-month study in 155 hypogonadal males between 18 and 65 years of age with documented hypogonadism, as defined by a below normal serum testosterone level (≤281 ng/dL) and at least one sign or symptom of testosterone deficiency. In the efficacy population (n=139), 88 percent of hypogonadal men treated with KYZATREX achieved a mean plasma total testosterone concentration (Cavg) over 24 hours within the normal range (222-800 ng/dL) on the final pharmacokinetic (PK) visit of the study at Day 90 (primary endpoint). Based on exploratory endpoints, patients who received KYZATREX reported improvements in quality of life, energy/fatigue, erectile function, intercourse satisfaction, and positive mood. The most common side effect reported in ≥2 percent of KYZATREX patients was increased blood pressure (2.6%). The safety and efficacy of KYZATREX in males less than 18 years old have not been established. Please see additional Important Safety Information below, including Boxed Warning for potential increased blood pressure, for KYZATREX or visit . About Marius Pharmaceuticals Marius Pharmaceuticals strives to better the lives of men and women by focusing on therapies designed for hypogonadism or Testosterone Deficiency. Their vision is to holistically improve metabolic health and mitigate significant unnecessary costs to the global healthcare system. For more information, please visit . Important Safety Information for KYZATREX® (testosterone undecanoate) Use KYZATREX (testosterone undecanoate) is a prescription drug that is used to treat adult men who have low or no testosterone levels due to certain medical conditions. KYZATREX is a controlled substance (CIII) because it contains testosterone. It is not known if KYZATREX is safe or effective in males younger than 18 years old. Improper use may affect bone growth in children. KYZATREX is not meant for use by women. Important Safety Information for KYZATREX® (testosterone undecanoate) KYZATREX can increase blood pressure, which can increase the risk of having a heart attack or stroke and can increase risk of death due to a heart attack or stroke. Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke. If your blood pressure increases while on KYZATREX, blood pressure medicines may need to be started. If you are currently taking blood pressure medicines, they may need to be changed or new blood pressure medicines may need to be added to control your blood pressure. If your blood pressure cannot be controlled, KYZATREX may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with KYZATREX. Do not take KYZATREX if you: have breast cancer; have or might have prostate cancer; are a woman who is pregnant (KYZATREX may harm your unborn baby); are allergic to KYZATREX or any of its ingredients; or have low testosterone without certain medical conditions (e.g., do not take KYZATREX if you have low testosterone due to age). Before you take KYZATREX, tell your healthcare provider about all of your medical conditions, including if you: have high blood pressure or are treated for high blood pressure; have a history of diabetes; have heart problems; have high red blood cell count (hematocrit) or high hemoglobin laboratory value; have urinary problems due to an enlarged prostate; have liver or kidney problems; or have problems breathing while you sleep (sleep apnea). Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking KYZATREX with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin; medicines that decrease blood clotting (blood thinners); corticosteroids; or medicines that increase blood pressure, such as some cold medicine and pain medicines. KYZATREX may cause other serious side effects including: Increase in red blood cell count (hematocrit) or hemoglobin, which can increase the risk of blood clots, strokes, and heart attacks. You may need to stop KYZATREX if your red blood cell count increases. If you already have an enlarged prostate, your signs and symptoms may worsen while taking KYZATREX. These may include: increased urination at night; trouble starting your urine stream; urinating many times during the day; urge to go to the bathroom right away; a urine accident; inability to pass urine or weak urine flow. Increased risk of prostate cancer. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Abuse. Testosterone can be abused when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects. In large doses, KYZATREX may lower your sperm count. Liver problems. Symptoms of liver problems may include: nausea or vomiting; yellowing of your skin or whites of your eyes; dark urine; pain on the right side of your stomach area (abdominal pain). Swelling of your ankles, feet, or body (edema), with or without heart failure. Enlarged or painful breasts. Breathing problems while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effect of KYZATREX is high blood pressure. Other side effects may include headache, joint or back pain, diarrhea, increased red blood cell count, anxiety, constipation, swelling of the legs, and increased prostate specific antigen (PSA) levels. These are not all the possible side effects of KYZATREX. For more information, ask your healthcare provider or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. You may also report side effects to Marius by calling 1-833-949-5040. Keep KYZATREX and all medicines out of the reach of children. See Full Prescribing Information and Medication Guide for KYZATREX. References: Bernstein JS, Dhingra O. "A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product." Ther Adv Urol. 2024;16:1-17. 2024; doi:10.1177/17562872241241864 Peterson MD, Belakovskiy A, McGrath R, Yarrow JF. Testosterone deficiency, weakness, and multimorbidity in men. Sci Rep. 2018;8(1):5897. doi:10.1038/s41598-018-24347-6 Thomas G. Travison TG, Araujo AB, O'Donnell AB, et al., Andre B. Araujo, Amy B. O'Donnell, Varant Kupelian, John B. McKinlay, A Population-Level Decline in Serum Testosterone Levels in American Men, J Clin Endocrinol Metab. January 2007, 92(1):196-202 Krakowsky Y, Grober E. Testosterone deficiency – Establishing a Biochemical Diagnosis. EJIFCC. 2015 Mar; 26(2): 105–113.PMID: 27683486; PMCID: PMC4975356. Accessed 9 Feb. 2024. Media Contact: 5W Public Relations [email protected] 212-999-5585 SOURCE Marius Pharmaceuticals