Osteitis Deformans

Recently, the Novo Nordisk team published an article in the Journal of Medicinal Chemistry, detailing the development of a long-acting, selective human amylin analog, NN1213, and its preclinical study data for weight management. Amylin is a pancreatic peptide consisting of 37 amino acids that is co-stored and co-secreted with insulin in response to nutrient intake. Post-secretion, amylin activates receptors in the posterior brain and hypothalamus, inducing satiety and affecting glucose control by inhibiting meal-stimulated glucagon secretion (in non-hypoglycemic states) and delaying gastric emptying. These biological effects support the research and development of optimized amylin analogs for use in weight management and diabetes treatment. Indeed, since 2005, the amylin analog pramlintide (Symlin) has been available on the U.S. market as a supplementation to insulin, helping diabetic patients who need additional blood glucose control support. Moreover, Novo Nordisk's long-acting but non-selective amylin analog, cagrilintide, has been shown to effectively reduce weight, either alone or in combination with a long-acting glucagon-like peptide-1 (GLP-1) analog, semaglutide. Amylin belongs to the calcitonin peptide family, which also includes calcitonin, α and β-type calcitonin gene-related peptides (CGRP), adrenomedullin 1, and adrenomedullin 2. These peptides act as ligands for a family of G-protein-coupled receptors (GPCRs), including the calcitonin receptor (CTR), a calcitonin receptor-like receptor bound to one of three receptor activity-modifying proteins (RAMP1-3). The peptides and receptors of the calcitonin peptide family are associated with various biological functions including regulating blood flow, bone metabolism, and energy metabolism. Salmon calcitonin (sCT) shares approximately 50% sequence similarity with mammalian calcitonins and is chemically more stable with a lower propensity for fibril formation. It is a potent and non-selective agonist of AMYR and CTR receptors. sCT is marketed under the names Miacalcin (in the USA) and Miacalcic (in the EU), and has been used for decades to treat postmenopausal osteoporosis, Paget's disease, and other bone disorders. In addition to achieving AMYR selectivity, a major obstacle in the pharmaceutical development of insulin is the inherent instability of the peptide, including its tendency to form fibrils and chemical degradation, which also needs to be addressed to achieve a molecule with drug-like properties. The amino acid sequence of human insulin allows the process of misfolding to take place, where monomeric insulin initially forms soluble oligomers rich in β-sheet structures, which might be cytotoxic. Over time, these oligomers may mature into extended structures with a high content of β-sheet chains, eventually forming insoluble protein aggregates that are histologically visible as amyloid fibrils in the islets of Type 2 diabetes patients. These toxic oligomer species are associated with β-cell death and the progression of Type 2 diabetes. Preventing fibril formation and improving β-cell survival and glucose control are related and have been demonstrated in preclinical models. Researchers have explored a series of amino acid mutations and modifications, including replacing the 21st position with proline and various acylation modifications at different positions. In vivo peptide screening tested the ability of peptides to reduce appetite in rats via a single subcutaneous injection for up to 48 hours, with peptides 6, 11, 17, 20, and 21 showing sustained effects from 24 to 48 hours post-injection. When the isoelectric point (pI) is higher, the duration of action tends to shorten, possibly indicating reduced binding of the positively charged compounds with albumin. Peptide 21, due to its selectivity and prolonged effect, represents the best choice in this series, combining physical and chemical stability with AMYR selectivity and demonstrating promising in vivo efficacy. Peptide 21, now referred to as NN1213, has been selected for further in vitro and in vivo characterization studies. In rats and dogs, a single dose of NN1213 reduced appetite in a dose-dependent manner with prolonged effects. Consistent with the effects on appetite, studies in obese rats showed that daily administration of NN1213 led to a dose-dependent decrease in body weight over 21 days. MRI imaging revealed that this was primarily due to reduced fat mass, while lean mass remained largely unchanged. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Reference https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jmedchem.4c00022

TYMLOS®demonstrated a lower incidence of hip fracture and non-vertebral fracture compared to teriparatide in women with osteoporosis 50 years and older (n=43,352) in this analysis of real-world data BOSTON, MA / ACCESSWIRE / April 16, 2024 / Radius Pharmaceuticals, Inc., a wholly owned subsidiary of Radius Health, Inc. ("Radius" or the "Company"), a specialty biopharmaceutical company focused on bone health, presented real-world evidence from an analysis comparing the effectiveness of TYMLOS® (ABL) to teriparatide (TPTD) in women with osteoporosis ages 50 years and older who were new to anabolic therapy (n=43,352). In this analysis of over 18-months of treatment, abaloparatide demonstrated a lower incidence of hip fracture and non-vertebral fracture compared to teriparatide. Hip fractures were reported in 1.1% of women in the ABL cohort and 1.4% of women in the TPTD cohort (HR [95% CI] 0.83 [0.70, 0.98]; P=0.03). Nonvertebral fractures were reported in 4.4% of women in the ABL cohort and 5.0% of women in the TPTD cohort (0.88 [0.80, 0.96]; P=0.003). Major cardiovascular events were balanced between cohorts.1 "The real-world data presented further supports the favorable efficacy and safety pro TYMLOS and why it is an important treatment option in the management of osteoporosis," said Dr. Felicia Cosman, Professor of Medicine at Columbia University College of Physicians and Surgeons in New York, NY, an osteoporosis specialist and clinical scientist and Co-Editor in Chief of the Journal Osteoporosis International. "Harnessing real-world evidence from everyday clinical settings affords clinicians the opportunity to uncover insights that can help guide treatment decisions." The data was presented in an abstract and oral presentation at the 24th Edition of the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO) in London, on April 12th, 2024. This real-world retrospective observational cohort study identified women 50 years and older, newly initiated on anabolic therapy with ABL or TPTD between May 1, 2017, and Dec 31, 2021.This analysis included pre-specified outcomes and utilized propensity score matching to help balance the characteristics in each treatment group; patients were well matched on 73 baseline parameters.1 Patients were identified using anonymized claims data from the Symphony Health Patient Source, Osteoporosis Patient Transactional Datasets. This is a disease specific subset of Integrated Dataverse® which includes data from over 307 million active patients. "We are very pleased to share the results of this analysis, as it further demonstrates the value of TYMLOS in the treatment of women with osteoporosis," said Scott Briggs, Chief Executive Officer of Radius. "Radius is committed to supporting men and postmenopausal women with osteoporosis, their families, and healthcare providers through our ongoing educational efforts as well as by generating data to support informed healthcare decision making." Real World Evidence: It is important to consider the limitations of RWE. RWE data sources may have incomplete information, leading to challenges in identifying and characterizing specific populations accurately. The source and type of RWE may limit the generalizability of the endpoints to broader populations/settings. RWE should be used in supplement to clinical trial evidence to support healthcare decision making. Due to data limitations, mortality data was not available in this dataset. There are no head-to-head randomized controlled clinical trials comparing abaloparatide and teriparatide. INDICATONS and IMPORTANT SAFETY INFORMATION INDICATIONS TYMLOS is indicated for: the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures, and the treatment to increase bone density in men withosteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy. IMPORTANT SAFETY INFORMATION2 Contraindications: TYMLOSis contraindicated in patients with a history of systemic hypersensitivity to abaloparatide or to any component of the product formulation. Reactions have included anaphylaxis, dyspnea, and urticaria. Risk of Osteosarcoma: It is unknown whether TYMLOS will cause osteosarcoma in humans. Osteosarcoma has been reported in patients treated with a PTH-analog in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of TYMLOS use. Avoid use of TYMLOS for patients at an increased baseline risk for osteosarcoma including patients with open epiphysis (pediatric and young adult patients); metabolic bone diseases other than osteoporosis, including Paget's disease of the bone; bone metastases or a history of skeletal malignancies; prior external beam or implant radiation therapy involving the skeleton; or hereditary disorders predisposing to osteosarcoma. Orthostatic Hypotension: Orthostatic hypotension may occur with TYMLOS, typically within 4 hours of injection. Associated symptoms may include dizziness, palpitations, tachycardia, or nausea, and may resolve by having the patient lie down. For the first several doses, TYMLOS should be administered where the patient can sit or lie down if necessary. Hypercalcemia: TYMLOSmay cause hypercalcemia. TYMLOS is not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, because of the possibility of exacerbating hypercalcemia. Hypercalciuria and Urolithiasis: TYMLOSmay cause hypercalciuria. It is unknown whether TYMLOS may exacerbate urolithiasis in patients with active or a history of urolithiasis. If active urolithiasis or pre-existing hypercalciuria is suspected, measurement of urinary calcium excretion should be considered. Pregnancy and Lactation: TYMLOSis not indicated for use in females of reproductive potential. Adverse Reactions: The most common adverse reactions (incidence ≥2%) reported with TYMLOS in postmenopausal women with osteoporosis are hypercalciuria (11%), dizziness (10%), nausea (8%), headache (8%), palpitations (5%), fatigue (3%), upper abdominal pain (3%), and vertigo (2%). The most common adverse reactions (incidence ≥2%) reported with TYMLOS in men with osteoporosis are injection site erythema (13%), dizziness (9%), arthralgia (7%), injection site swelling (7%), injection site pain (6%), contusion (3%), abdominal distention (3%), diarrhea (3%), nausea (3%), abdominal pain (2%), and bone pain (2%). Please see full Prescribing Information. About Abaloparatide2 Abaloparatide (TYMLOS®) was approved in April 2017 by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, TYMLOS® reduces the risk of vertebral fractures and nonvertebral fractures. In December 2022, Abaloparatide (TYMLOS®) was approved for the treatment to increase bone density in men with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy. Abaloparatide is supplied as a single-patient multi-use prefilled pen designed to subcutaneously administer 80 micrograms per dose over a 30-day period. About Radius: Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health and related areas. Radius' lead product, TYMLOS® (abaloparatide) injection, was approved by the U.S. Food and Drug Administration in April 2017 for the treatment of postmenopausal women with osteoporosis at high risk for fracture, and in December 2022 to increase bone density in men with osteoporosis at high risk for fracture. Radius also recently announced an exclusive licensing and distribution agreement for the U.S. rights to BINOSTO® (alendronate sodium) effervescent tablet for oral solution, expanding the Company's presence in bone health. Reginster JY, et al. The comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: update of a real-world retrospective analysis. Presented at the WCO-IOF-ESCEO Annual Meeting, April 11-14, 2024 in London, UK. Accessed April 10, 2024. TYMLOS® [prescribing information]. Boston, MA: Radius Health, Inc. TYMLOS® Medication Guide. Radius Health, Inc.; Boston, MA. Contact: Sara Goldberg: Head of Communications Email: corporatecommunications@radiuspharm.com Phone: +1 (631) 379-8374 SOURCE: Radius Health, Inc. View the original press release on accesswire.com

FRIDAY, Jan. 12, 2024 -- For patients undergoing surveillance following diagnosis and treatment of ductal carcinoma in situ (DCIS), very few second breast cancers are detected by clinical breast examination by a physician, according to a study published online Dec. 28 in the Journal of the National Comprehensive Cancer Network . Bethany T. Waites, M.D., from the Kaiser Permanente San Francisco Medical Center, and colleagues performed a retrospective cohort study of patients with DCIS treated between Jan. 1, 2008, and Dec. 31, 2011, to assess the modes of detection of second cancers. The study cohort included 1,550 women (median age at diagnosis, 59 years), who were followed for a median of 10 years. During follow-up, 179 women (11.5 percent) were diagnosed with a second breast cancer: 43.0, 54.8, and 2.2 percent were ipsilateral, contralateral, and presented with distant metastases, respectively. Of the second cancers, 61.5, 36.3, and 2.2 percent were invasive, DCIS, and Paget disease, respectively. The researchers found that second breast cancers were imaging-detected, patient-detected, physician-detected, and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 74.3, 20.1, 2.2, and 3.4 percent of cases, respectively. "Our findings highlight the importance of mammogram screening and patient education regarding self-detection, and can inform future National Comprehensive Cancer Network recommendations for DCIS survivorship care," the authors write. Abstract/Full Text Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions. Posted January 2024 More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Drug Shortages Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.