Testosterone deficiency

Astellas Pharma’s enfortumab vedotin is a Nectin-4- targeted antibody-drug conjugate. Credit: BalkansCat / Shutterstock.com. The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted Astellas Pharma ’s supplemental biologics license application (sBLA) for enfortumab vedotin plus KEYTRUDA (pembrolizumab) for urothelial cancer. This combination therapy is aimed at treating adult patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Enfortumab vedotin is a targeted antibody-drug conjugate (ADC) directed against the Nectin-4 protein. The potential approval for the combination regimen could revolutionise the standard of care for first-line la/mUC, offering an alternative to the platinum-containing chemotherapy that is currently administered. The sBLA is based on the data from the randomised, open-label, controlled Phase III EV-302 clinical trial, also known as KEYNOTE-A39. See Also: Arvinas gets grant for treatment of prostate cancer with specific compounds Chong Kun Dang Pharmaceutical gets grant for injectable composition of testosterone undecanoate for testosterone deficiency treatment This study compared enfortumab vedotin in combination with pembrolizumab to platinum-containing chemotherapy in 886 patients. Overall survival (OS) and progression-free survival (PFS) were the trial’s primary outcomes. Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety profiles. The results demonstrated that the combination of enfortumab vedotin with pembrolizumab significantly improved OS and PFS, with meaningful clinical outcomes when compared to the standard chemotherapy regimen. The safety profile of the combination therapy was in line with prior reports without any new safety concerns identified. In addition to the CDE’s review, the NMPA is considering enfortumab vedotin as a treatment option for la/mUC patients who have previously undergone therapy with a PD-1/L1 inhibitor and platinum-based chemotherapy. Parallelly, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) and Japan’s Ministry of Health, Labour and Welfare (MHLW) are also reviewing the combination regimen. In December last year, the US Food and Drug Administration granted approval for this combination therapy . Astellas Oncology Development head and senior vice-president Ahsan Arozullah said: “Locally advanced or metastatic urothelial cancer is a life-threatening condition in China with nearly half of those diagnosed succumbing to the disease. “The CDE’s acceptance of our sBLA for enfortumab vedotin and pembrolizumab brings us one step closer to delivering a much-needed, innovative new treatment option for this patient population.”

A groundbreaking study has unveiled a significant link between anxiety disorders and a brain receptor known as TACR3, as well as testosterone. A groundbreaking study has unveiled a significant link between anxiety disorders and a brain receptor known as TACR3, as well as testosterone. Prof. Shira Knafo, head of the Molecular Cognitive Lab at Ben-Gurion University, led the research published last month in the journal Molecular Psychiatry. Anxiety is a common response to stress, but for those dealing with anxiety disorders, it can significantly impact daily life. Clinical evidence has hinted at a close connection between low testosterone levels and anxiety, particularly in men with hypogonadism, a condition characterized by reduced sexual function. However, the precise nature of this relationship has remained unclear until now. Prof. Knafo discovered male rodents exhibiting exceedingly high anxiety levels had notably lower levels of a specific receptor called TACR3 in their hippocampus. The hippocampus is a brain region closely associated with learning and memory processes. TACR3 is part of the tachykinin receptor family and responds to a substance known as neurokinin. This observation piqued the researchers' curiosity and was the foundation for an in-depth investigation into the link between TACR3 deficiency, sex hormones, anxiety, and synaptic plasticity. The rodents were classified based on their behavior in a standard elevated plus maze test measuring anxiety levels. Subsequently, their hippocampi were isolated and underwent gene expression analysis to identify genes with varying expressions between rodents with extremely low anxiety and those with severe anxiety. One gene that stood out was TACR3. Previous research had revealed that mutations in genes associated with TACR3 led to a condition known as "congenital hypogonadism," resulting in reduced sex hormone production, including testosterone. Notably, young men with low testosterone often experienced delayed sexual development, accompanied by depression and heightened anxiety. This pairing led researchers to investigate the role of TACR3 further. Prof. Knafo and her team were aided in their research by two innovative tools they crafted themselves. The first, known as FORTIS, detects changes in receptors critical for neuronal communication within living neurons. By utilizing FORTIS, they demonstrated that inhibiting TACR3 resulted in a sharp increase in these receptors on the cell surface, blocking the parallel process of long-term synaptic strengthening, known as LTP. The second pioneering tool employed was a novel application of cross-correlation to measure neuronal connectivity within a multi-electrode array system. This tool played a pivotal role in uncovering the profound impact of TACR3 manipulations on synaptic plasticity. Synaptic plasticity refers to the ability of synapses, the connections between brain cells, to change their strength and efficiency. This dynamic process is fundamental for the brain's adaptation to the environment. Through synaptic plasticity, the brain can reorganize its neural circuitry in response to new experiences. This flexibility allows for the modification of synaptic connections, enabling neurons to strengthen or weaken their communication over time. Essentially, synaptic plasticity is a key mechanism by which the brain encodes and stores information, adapting continuously to the ever-changing external stimuli and internal states. Importantly, it revealed that deficiencies stemming from TACR3 inactivity could be efficiently rectified through testosterone administration, offering hope for novel approaches to address challenges related to anxiety associated with testosterone deficiency. TACR3 is seemingly a central player in bridging anxiety and testosterone. The researchers have unraveled the complex mechanisms behind anxiety and opened avenues for novel therapies, including testosterone treatments, that could improve the quality of life for individuals grappling with sexual development disorders and associated anxiety and depression. Prof. Knafo is a member of the Department of Physiology and Cell Biology in the Faculty of Health Sciences as well as The National Institute for Biotechnology in the Negev. The research was supported by the Israel Science Foundation (Grant no. 536/19).

[09-January-2024] RALEIGH, N.C., Jan. 9, 2024 /PRNewswire/ -- Marius Pharmaceuticals, a pharmaceutical company focused on developing innovative therapies for testosterone deficiency, today announced it has initiated a pilot study to better understand the effect of oral testosterone replacement therapy, KYZATREX® (testosterone undecanoate), on spermatogenesis in adult males. KYZATREX is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. While it is generally accepted that TRT in males decreases spermatogenesis, which occurs through suppression of the hypothalamic-pituitary-gonadal axis, most data are derived from traditional routes of administration of TRT (e.g., injections, patches, gels, implantable pellets, etc.). This study will be the first of its kind to specifically examine the effects of an oral TRT, like KYZATREX, on spermatogenesis. Importantly, the American Urological Association currently recommends that physicians prescribing TRT inform their patients of the risks of the therapy on fertility. "We are eager to begin this new pilot study, as finding an option of TRT that does not reduce fertility in men would be a significant milestone in the field of andrology and society as a whole," said Andrew Sun, M.D., Director at the Center for Men's Health at Urology Partners of North Texas and Chief Medical Advisor for Marius Pharmaceuticals. "Too many men are suffering in silence from the effects of testosterone deficiency, and the results from this study could help us better understand the effects of oral TRT on spermatogenesis, which might potentially benefit a subset of men; those who are looking to start a family while still treating their low T." Led by principal investigator Dr. Mohit Khera, Director of the Laboratory for Andrology Research Baylor College of Medicine, the study will enroll 20 male patients, ages 18-49 years old, who meet the American Urological Association's criteria for hypogonadism and who have not previously used TRT. "Historically, testosterone products have been known to impair sperm production. Thus, many young hypogonadal men planning to achieve a pregnancy are unable to use testosterone due to an increased risk of suppressing their sperm production," said Dr. Khera. "Identifying testosterone therapy that could potentially not suppress sperm production would be a significant advancement in the way we treat these hypogonadal men." Participating patients will receive 200-400mg of KYZATREX BID for three months. Two semen analyses will be performed at baseline, one month, and three months, to assess any changes in each patient's sperm count. Blood draws will also be taken at each of these timepoints to measure testosterone, hormones, lipids, and hematocrit. There will also be an additional blood draw two weeks after starting the therapy to support drug titration to reach therapeutic levels. Additionally, patients will receive the IIEF, PHQ-9, and SF36 questionnaires at baseline and at the conclusion of the study to assess symptoms of low testosterone. This pilot 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 . 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.