作者: Naciu, Anda Mihaela ; Anastasilakis, Athanasios D ; Tsourdi, Elena ; Tabacco, Gaia ; Paccou, Julien ; Yavropoulou, Maria P ; Makras, Polyzois ; Palermo, Andrea

AbstractOsteoanabolic agents are used as a first line treatment in patients at high fracture risk. The PTH receptor 1 (PTH1R) agonists teriparatide (TPTD) and abaloparatide (ABL) increase bone formation, bone mineral density (BMD), and bone strength by activating PTH receptors on osteoblasts. Romosozumab (ROMO), a humanized monoclonal antibody against sclerostin, dramatically but transiently stimulates bone formation and persistently reduces bone resorption. Osteoanabolic agents increase BMD and bone strength while being more effective than antiresorptives in reducing fracture risk in postmenopausal women. However, direct comparisons of the antifracture benefits of osteoanabolic therapies are limited. In a direct comparison of TPTD and ABL, the latter resulted in greater BMD increases at the hip. While no differences in vertebral or non-vertebral fracture risk were observed between the two drugs, ABL led to a greater reduction of major osteoporotic fractures. Adverse event profiles were similar between the two agents except for hypercalcemia, which occurred more often with TPTD. No direct comparisons of fracture risk reduction between ROMO and the PTH1R agonists exist. Individual studies have shown greater increases in BMD and bone strength with ROMO compared with TPTD in treatment-naive women and in women previously treated with bisphosphonates. Some safety aspects, such as a history of tumor precluding the use of PTH1R agonists, and a history of major cardiovascular events precluding the use of ROMO, should also be considered when choosing between these agents. Finally, convenience of administration, reimbursement by national health systems and length of clinical experience may influence patient choice.

2024-05-01·The Journal of the American Board of Family Medicine

Shoring Up Osteoporosis Management: A Fresh Start?

Article

作者: Ulmer, Ansley ; Cardon, Brock ; Furr, Noah

Anabolic bone agents, such as parathyroid hormone receptor agonists (teriparatide and abaloparatide) and sclerostin-inhibiting monoclonal antibody (romosozumab), are superior at preventing clinically significant fractures and/or vertebral fractures in women with and without severe osteoporosis compared with bisphosphonates.

2023-05-02·BMJ (Clinical research ed.)

Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.

Review

作者: Lems, Willem Frederik ; Ussing, Anja ; Nogues, Xavier ; Kurth, Andreas ; Händel, Mina Nicole ; Cardoso, Isabel ; Abrahamsen, Bo ; Ferrari, Serge Livio ; Thomas, Thierry ; Brandi, Maria Luisa ; Javaid, Muhammad Kassim ; Nielsen, Sabrina Mai ; Prieto-Alhambra, Daniel ; Hadji, Peyman ; von Bülow, Cecilie ; Christensen, Robin ; Rohde, Jeanett Friis ; Langdahl, Bente ; Diez-Perez, Adolfo ; Minisola, Salvatore ; Roux, Christian ; Body, Jean-Jacques

OBJECTIVETo review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors.DESIGNSystematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.DATA SOURCESMedline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator.ELIGIBILITY CRITERIA FOR SELECTING STUDIESRandomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events.RESULTSThe results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision.CONCLUSIONSThe evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures.SYSTEMATIC REVIEW REGISTRATIONPROSPERO CRD42019128391.

项与 PTH-IA 相关的新闻（医药）

2023-06-07

·GlobeNewswire-Health Care

Amolyt Pharma to Host Hybrid Key Opinion Leader Event on Eneboparatide, a PTHR1 Agonist Entering Phase 3 for the Treatment of Hypoparathyroidism, in Chicago on June 16, 2023

LYON, France and CAMBRIDGE, Mass., June 07, 2023 (GLOBE NEWSWIRE) -- Amolyt Pharma, a global company specialized in developing therapeutic peptides for rare endocrine and related diseases, today announced that it will host an in-person key opinion leader (KOL) event on eneboparatide, the company’s investigational lead product candidate for the treatment of hypoparathyroidism on Friday, June 16, 2023 at 8:30 AM CT (9:30 AM ET) at the Sheraton Grand Chicago Riverwalk in Chicago, IL. The event will also be webcasted for those who are unable to attend in person. The event will feature Aliya Khan, M.D., FRCPC, FACP, FACE, FASBMR (McMaster University Medical Centre), who will discuss the unmet medical needs for patients living with hypoparathyroidism and present the full results of the Phase 2a trial of eneboparatide, a parathyroid hormone receptor 1 (PTHR1) agonist with a novel mechanism of action. Patty Keating, patient and Chairwoman of the HypoPARAthyroidism Association, will share her personal experience living with the disease and challenges with the current standard of care. Mark Sumeray, M.D., chief medical officer of Amolyt Pharma, will provide an update on the Calypso study, a Phase 3 clinical trial of eneboparatide for the treatment of patients with hypoparathyroidism. A live question and answer session will follow the formal presentations. To register for the event, please click here. About HypoparathyroidismHypoparathyroidism is defined by a deficiency of parathyroid hormone (PTH) that results in decreased calcium and elevated phosphorus levels in the blood. Approximately 80% of the estimated 80,000 people in the U.S. and 110,000 in the European Union with hypoparathyroidism are women. Despite available treatments, patients experience persistent, life-altering symptoms and often develop complications and comorbidities that diminish quality of life and create segments of the patient population with specific clinical needs. Clinical manifestations of hypoparathyroidism impact many tissues and organ systems, in particular, the kidneys and bone. 17% of patients with hypoparathyroidism have osteopenia or osteoporosis and 53% are peri- or postmenopausal women with an increased risk of developing osteoporosis. Approximately 26% of patients with hypoparathyroidism have chronic kidney disease or failure, highlighting the importance of reducing urinary calcium excretion as a key treatment goal. About EneboparatideEneboparatide is an investigational therapeutic peptide designed to target a specific conformation of the parathyroid hormone (PTH) receptor to produce sustained and stable levels of calcium in the blood and thereby manage the symptoms of hypoparathyroidism, and to limit urine calcium excretion by restoring calcium reabsorption by the kidney, with the goal of consequently preventing chronic kidney disease. In addition to its unique receptor profile, eneboparatide is also designed to have a short half-life to potentially preserve bone integrity, an important potential benefit, since the majority of patients are peri- and postmenopausal women with an increased risk of developing osteoporosis. About Amolyt PharmaAmolyt Pharma, a clinical stage biotechnology company, is building on its team’s established expertise to deliver life-changing treatments to patients suffering from rare endocrine and related diseases. Its development portfolio includes eneboparatide (AZP-3601), a long-acting PTH1 receptor agonist as a potential treatment for hypoparathyroidism, and AZP-3813, a peptide growth hormone receptor antagonist for the potential treatment of acromegaly. Amolyt Pharma aims to further expand and develop its portfolio by leveraging its global network in the field of endocrinology and with support from a strong syndicate of international investors. To learn more, visit https://amolytpharma.com/ or follow us on Twitter and LinkedIn. Media Inquiries:Jordyn TemperatoLifeSci Communicationsjtemperato@lifescicomms.com Investors Inquiries:Ashley RobinsonLifeSci Advisors, LLCarr@lifesciadvisors.com+1.617.430.7577

临床2期临床3期

2023-05-05

·GlobeNewswire-Health Care

Amolyt Pharma Announces Abstracts Accepted for Presentation at ECE and ENDO

LYON, France and CAMBRIDGE, Mass., May 05, 2023 (GLOBE NEWSWIRE) -- Amolyt Pharma, a global company specialized in developing therapeutic peptides for rare endocrine and related diseases, today announced that the company has had multiple abstracts accepted for presentation at the 25th European Congress of Endocrinology (ECE), which is being held May 13-16 in Istanbul, Turkey, and at the 2023 Endocrine Society Meeting (ENDO), which is being held June 15-18 in Chicago, Illinois. These presentations cover both of Amolyt’s development programs, eneboparatide entering Phase 3 for hypoparathyroidism and AZP-3813 entering Phase 1 for acromegaly. Details of the presentations are as follows: 25th European Congress of Endocrinology (ECE) – May 13-16, Istanbul, Turkey Title: Eneboparatide, a Novel PTH-1 Receptor Agonist, Has No Impact on Bone Parameters Following Chronic Treatment of Non-Human PrimatesFormat: Oral Presentation Session: Oral Communications 8: Calcium and BoneDate: Monday, May 15, 2023Time: 2:00-3:00 p.m. CEST Title: Eneboparatide, a Novel PTH-1 Receptor Agonist, Induces Rapid Reduction and Normalization of Urinary Calcium in Chronic Hypoparathyroid PatientsFormat: Poster / Rapid Oral Presentation Session: Rapid Communications 8: Calcium and Bone Date: Monday, May 15, 2023Time: 3:05-3:40 p.m. CESTPoster Display: 9:40 a.m. CEST on Sunday, May 14 – 3:30 p.m. CEST on Tuesday, May 16 Title: Treatment of Chronic Hypoparathyroidism by Eneboparatide, a Novel PTH Receptor-1 Agonist: Results from a Phase 2a StudyFormat: Poster / Rapid Oral PresentationSession: Rapid Communications 8: Calcium and BoneDate: Monday, May 15, 2023Time: 3:05-3:40 p.m. CESTPoster Display: 9:40 a.m. CEST on Sunday, May 14 – 3:30 p.m. CEST on Tuesday, May 16 Title: AZP-3813, a Bicyclic, 16-Amino Acid Peptide Antagonist of the Human Growth Hormone Receptor, Effectively Suppresses IGF1 in Beagle Dogs Format: Poster / Rapid Oral PresentationSession: Rapid Communication 7: Pituitary and Neuroendocrinology 2Date: Monday, May 15, 2023Time: 3:05-3:40 p.m. CEST Poster Display: 9:40 a.m. CEST on Sunday, May 14 – 3:30 p.m. CEST on Tuesday, May 16 2023 Endocrine Society Meeting (ENDO) – June 15-18, Chicago, Illinois Title: Repeated Treatment with AZP-3813, a Bicyclic, 16-Amino Acid Peptide Antagonist of the Human Growth Hormone Receptor, Induces Enhanced Suppression of IGF1 in Beagle DogsFormat: Poster Presentation Session: Neuroendocrinology: Neuroendocrinology and Pituitary: Growth Hormone and Acromegaly - Basic and TranslationalDate: Thursday, June 15, 2023Time: 12:30-1:30 p.m. CSTPoster Display: 9:00 a.m. – 3:00 p.m. CST on Thursday, June 15 Title: Treatment of Chronic Hypoparathyroidism with Eneboparatide (AZP-3601), a Novel PTH 1 Receptor Agonist: Results from a Phase 2 TrialFormat: Oral Presentation Session: Bone 2 - PTH-Relevant Biology, Pathophysiology, and TherapeuticsDate: Saturday, June 17, 2023Time: 9:45-11:15 a.m. CST Title: Variations in Clinical Practice Patterns for HypoparathyroidismFormat: Poster Presentation Session: Bone and Mineral Metabolism: HypoparathyroidismDate: Saturday, June 17, 2023Time: 1:00-2:00 p.m. CSTPoster Display: 9:00 a.m. – 3:00 p.m. CST on Saturday, June 17 Title: AZP-3601, a Novel PTH 1 Receptor Agonist, Induces Rapid Reduction and Normalization of Urinary Calcium in Chronic Hypoparathyroid PatientsFormat: Poster PresentationSession: Bone and Mineral Metabolism: HypoparathyroidismDate: Saturday, June 17, 2023Time: 1:00-2:00 p.m. CSTPoster Display: 9:00 a.m. – 3:00 p.m. CST on Saturday, June 17 About Amolyt Pharma Amolyt Pharma, a clinical stage biotechnology company, is building on its team’s established expertise to deliver life-changing treatments to patients suffering from rare endocrine and related diseases. Its development portfolio includes eneboparatide (AZP-3601), a long-acting PTH1 receptor agonist as a potential treatment for hypoparathyroidism, and AZP-3813, a peptide growth hormone receptor antagonist for the potential treatment of acromegaly. Amolyt Pharma aims to further expand and develop its portfolio by leveraging its global network in the field of endocrinology and with support from a strong syndicate of international investors. To learn more, visit https://amolytpharma.com/ or follow us on Twitter and LinkedIn. Media Inquiries: Jordyn TemperatoLifeSci Communications jtemperato@lifescicomms.com Investors Inquiries:Ashley RobinsonLifeSci Advisors, LLCarr@lifesciadvisors.com+1.617.430.7577

临床2期临床3期

2023-05-02

·GlobeNewswire-Health Care

Amolyt Pharma Announces Phase 3 Clinical Trial of Eneboparatide for the Treatment of Hypoparathyroidism following Positive End of Phase 2 Meeting with FDA

The Calypso trial is expected to be the largest Phase 3 trial to date conducted in hypoparathyroidism with topline data expected by end of 2024 In addition to serum calcium control and elimination of standard of care, the study will also assess normalization of urinary calcium as a key secondary efficacy endpoint The effect of eneboparatide on bone quantity and quality will also be evaluated Calypso design builds on the findings from the Phase 2a trial in relation to control of serum calcium, discontinuation of oral supplements, normalization of hypercalciuria and induction of a balanced bone turnover. LYON, France and CAMBRIDGE, Mass., May 02, 2023 (GLOBE NEWSWIRE) -- Amolyt Pharma, a global company specialized in developing therapeutic peptides for rare endocrine and related diseases, today announced that it will initiate its Phase 3 clinical trial of eneboparatide, a long-acting parathyroid hormone 1 (PTH1) receptor agonist, in patients with hypoparathyroidism following the receipt of End-of-Phase 2 guidance from the U.S. Food and Drug Administration (FDA). “We appreciate the constructive discussions with the FDA during the End-of-Phase 2 meeting and have designed our trial in line with the Agency’s guidance. We believe the Calypso study will be the largest prospective randomized clinical trial in hypoparathyroidism to date, representing a major milestone for the patient community as well as for Amolyt Pharma,” said Thierry Abribat, Ph.D., founder and chief executive officer of Amolyt Pharma. “We look forward to further evaluating the clinical potential of eneboparatide to uniquely address key treatment goals in hypoparathyroidism. On the heels of our recently announced $138M Series C financing, we look forward to diligently executing this trial with the aim to announce topline data by the end of 2024.” Mark Sumeray, M.D., chief medical officer of Amolyt Pharma, added, “Standard of care, which is high doses of oral calcium and vitamin D supplements, often fails to normalize serum calcium levels and exacerbates hypercalciuria, leading to progressive kidney dysfunction and failure from calcium deposition and kidney stones. In this Phase 3 trial, we will evaluate the efficacy of eneboparatide with respect to control of serum calcium, elimination of standard of care and improvement of symptoms. In addition, we have specified normalization of urinary calcium excretion in hypercalciuric patients as the first key secondary efficacy endpoint. We have also included exploratory endpoints assessing bone quantity and quality, since many patients with hypoparathyroidism have or are at risk of developing osteopenia or osteoporosis.” Calypso is a Phase 3 multicenter, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of eneboparatide in patients with chronic hypoparathyroidism. Approximately 165 patients treated with standard of care will be randomized in a 2:1 ratio to receive eneboparatide or placebo. The primary efficacy endpoint is the proportion of patients that achieve albumin-adjusted serum calcium within the normal range and independence from standard of care after 24 weeks of treatment. The secondary efficacy endpoints include normalization of 24-hour urinary calcium in patients with hypercalciuria at baseline and assessment of patient-reported outcomes that reflect symptoms associated with physical and cognitive function and impact on quality of life. Additional exploratory endpoints assess bone quantity and quality using DXA scanning and high resolution peripheral quantitative CT scanning. After the initial 24-week placebo-controlled period, all patients will be treated with eneboparatide in an open-label extension phase for an additional 28 weeks. The Calypso trial aims to build on the findings of our Phase 2a trial, which demonstrated that eneboparatide maintained mean serum calcium within the target range, allowing discontinuation of oral supplements in 93% of patients; induced a balanced increase in bone biomarkers that was consistent with restoration of more physiologic bone turnover; and rapidly normalized 24-hour urinary calcium excretion in all but one patient. The Calypso trial will be conducted in more than 50 centers in the United States, Europe, Canada, and the United Kingdom. About HypoparathyroidismHypoparathyroidism is defined by a deficiency of parathyroid hormone (PTH) that results in decreased calcium and elevated phosphorus levels in the blood. Approximately 80% of the estimated 80,000 people in the U.S. and 110,000 in the European Union with hypoparathyroidism are women. Despite available treatments, patients experience persistent, life-altering symptoms and often develop complications and comorbidities that diminish quality of life and create segments of the patient population with specific clinical needs. Clinical manifestations of hypoparathyroidism impact many tissues and organ systems, in particular the kidneys and bone. 17% of patients with hypoparathyroidism have osteopenia or osteoporosis and 53% are peri- or postmenopausal women with an increased risk of developing osteoporosis. Approximately 26% of patients with hypoparathyroidism have chronic kidney disease or failure, highlighting the importance of reducing urinary calcium excretion as a key treatment goal. About EneboparatideEneboparatide is an investigational therapeutic peptide designed to target a specific conformation of the parathyroid hormone (PTH) receptor to safely produce sustained and stable levels of calcium in the blood and thereby manage the symptoms of hypoparathyroidism, and to limit urine calcium excretion by restoring calcium reabsorption by the kidney, with the goal of consequently preventing chronic kidney disease. In addition to its unique receptor profile, eneboparatide is also designed to have a short half-life to potentially preserve bone integrity, an important benefit, since the majority of patients are peri- and postmenopausal women with an increased risk of developing osteoporosis. About Amolyt Pharma Amolyt Pharma, a clinical stage biotechnology company, is building on its team’s established expertise to deliver life-changing treatments to patients suffering from rare endocrine and related diseases. Its development portfolio includes eneboparatide (AZP-3601), a long-acting PTH1 receptor agonist as a potential treatment for hypoparathyroidism, and AZP-3813, a peptide growth hormone receptor antagonist for the potential treatment of acromegaly. Amolyt Pharma aims to further expand and develop its portfolio by leveraging its global network in the field of endocrinology and with support from a strong syndicate of international investors. To learn more, visit https://amolytpharma.com/ or follow us on Twitter and LinkedIn. Media Inquiries: Jordyn TemperatoLifeSci Communications jtemperato@lifescicomms.com Investors Inquiries:Ashley RobinsonLifeSci Advisors, LLCarr@lifesciadvisors.com+1.617.430.7577

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100 项与 PTH-IA 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
Jansen型干骺端软骨发育不良	药物发现	美国	National Institutes of Health	-
Jansen型干骺端软骨发育不良	药物发现	美国	National Center for Advancing Translational Sciences	-