Yorvipath (palopegteriparatide) / Ascendis, Teijin, Specialised Therap, Royalty - LARVOL DELTA

Palopegteriparatide Treatment for Hypoparathyroidism in Three Women with Autoimmune Polyglandular Syndrome (ASBMR 2025) - No abstract available

Clinical • Endocrine Disorders • Hypoparathyroidism • Immunology

Improved Skeletal Dynamics in Adults Treated with Palopegteriparatide for Chronic Hypoparathyroidism: 214-Week Results from the Phase 2 PaTH Forward Trial (ASBMR 2025) - No abstract available

Clinical • P2 data • Endocrine Disorders • Hypoparathyroidism

The Drug Update: Recent drug approvals, summer 2025 edition. (PubMed, Nurse Pract) - "This article highlights the following new medications: donanemab-azbt (Kisunla), nalmefene injection (Zurnai), epinephrine nasal spray (neffy), palopegteriparatide (Yorvipath), xanomeline and trospium chloride (Cobenfy), and sulopenem etzadroxil/probenecid (Orlynvah). Additionally, this article highlights the recent approval of obstructive sleep apnea as a new indication for tirzepatide (Zepbound) and chronic obstructive pulmonary disease as a new indication for dupilumab (Dupixent)."

Journal • Addiction (Opioid and Alcohol) • Allergy • Alzheimer's Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Endocrine Disorders • Hypoparathyroidism • Immunology • Obstructive Sleep Apnea • Psychiatry • Pulmonary Disease • Respiratory Diseases • Schizophrenia • Sleep Disorder

PaTHway60: A Phase 3 Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism (clinicaltrials.gov) - P3 | N=18 | Not yet recruiting | Sponsor: Ascendis Pharma Bone Diseases A/S

New P3 trial • Endocrine Disorders • Hypoparathyroidism

Switch From rhPTH1-84 to TransCon PTH With Individual Dose Adjustment in Adult Hypoparathyroidism-4-Week Results. (PubMed, J Endocr Soc) - "We hereby report the first clinical data on switching treatment from rhPTH1-84 to 18 µg TransCon PTH independent of the prior rhPTH1-84 dose. Our data support discrete adaptation of the starting dose depending on the prior rhPTH1-84 dosage."

Journal • Endocrine Disorders • Hypoparathyroidism

Chronic Hypoparathyroidism - Current and Emerging Therapies. (PubMed, Endocr Pract) - "Palopegteriparatide has a 60-hour half life and results in an infusion like PTH release profile...New molecules include an oral PTH1receptor agonist which is in phase 1 clinical trials. A weekly PTH molecule is also being evaluated in phase 2 clinical trials."

Journal • Review • Endocrine Disorders • Hypoparathyroidism

All Time Low: A Follow-Up Case Report On Basal Ganglia Calcification From Chronic Hypocalcemia Following Postsurgical Hypoparathyroidism (ENDO 2025) - "Palopegteriparatide and eneboparatide, both long-acting agents, are able to achieve normocalcemia while being independent from conventional therapy, and are well-tolerated. A newer and longer-acting agent, MBX 2109, in 2024 was on Phase 1 trial for tolerance and safety, aiming once-weekly PTH replacement. While Calcium and Vitamin D are the mainstay management in hypoPT, replacing PTH may now be considered in chronic hypocalcemia unresponsive to conventional treatment, aiming to avoid long-term and disabling complications."

Case report • Clinical • Endocrine Cancer • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Thyroid Gland Carcinoma

Therapeutic Management of ADH1 in a 16-year Old Boy Using Palopegteriparatide. (ENDO 2025) - "Previously, the patient was receiving alfacalcidol (1.25 mcg/day), CaCO3 (600 mg Ca/day), hydrochlorothiazide (12.5-6.25 mg), MgSO4 (260 mg Mg/day), and KCl (782 mg K/day)...Calcilytics (e.g., encaleret) should be the drugs of choice in the treatment of ADH1, but they are currently still the subject of/ under investigation (CALIBRATE trial)...The long-term effects of using long-acting PTHR1 analogs are currently unknown. However, this treatment should be considered in cases of severe abnormalities in calcium and phosphate levels that lead to calcium salt precipitation and subsequent organ dysfunction."

Cataract • Endocrine Disorders • Hypoparathyroidism • Infectious Disease • Metabolic Disorders • Nephrology • Ophthalmology • Pain • Renal Disease

Chronic PTH deficiency leads to impaired neural plasticity (ENDO 2025) - "A patient subgroup had TMS recordings repeated after initiating PTH treatment [3 subjects on PTH(1-34) and 3 subjects on Palopegteriparatide]... our findings suggest that hypoPT present a functional impairment of neural plasticity mechanisms. PTH replacement therapy seems to restore this impairment, but we believe that further comprehensive studies are needed."

Alzheimer's Disease • Cognitive Disorders • Endocrine Disorders • Fatigue • Hypoparathyroidism • Pain

Efficacy and Safety of Palopegteriparatide Treatment in Adults With Hypoparathyroidism: 3-Year Results From The Phase 3 PaTHway Trial (ENDO 2025) - "TEAEs were mostly grade 1 or 2, with no new safety signals identified. Conclusion Through year 3 of the PaTHway trial, retention rate was high and palopegteriparatide demonstrated consistent longer-term safety and efficacy, which included the maintenanceof serum and urine biochemistries within normal levels and sustained improvement in renal function."

Clinical • P3 data • Endocrine Disorders • Hypoparathyroidism

Asymptomatic Severe Recalcitrant Hypocalcemia treated with H1-34 teriparatide (ENDO 2025) - "Clinical Case: A 59-year-old woman with a history of multinodular goiter, osteoporosis, severe GERD on famotidine and gastric bypass surgery in 2020 presented for total thyroidectomy due to a Afirma suspicious nodule in May of 2024. While the hallmark of hypocalcemia is neuromuscular irritability our case demonstrates the importance of monitoring even in asymptomatic patients with low initial calcium and risk factors for decreased calcium absorption like gastric bypass and treated GERD with antacids. This case further supports use of teriparatide for refractory hypocalcemia. As new research emerges regarding the long-term safety of teriparatide, it may serve as a cost-effective alternative to recently approved but more expensive treatments like palopegteriparatide."

Cardiovascular • CNS Disorders • Endocrine Disorders • Epilepsy • Gastroesophageal Reflux Disease • Osteoporosis • Rheumatology

Best practice recommendations for the diagnosis and management of hypoparathyroidism. (PubMed, Metabolism) - "These best practice recommendations provide a framework for HypoPT diagnosis and management, emphasizing individualized care, role of DNA analysis in the diagnosis of nonsurgical HypoPT, and role of PTH or PTH analogue therapy as appropriate. They complement the 2022 international guidelines and incorporate updated therapeutic recommendations from the past 3 years including the positioning of the newly approved molecule palopegteriparatide based on recent clinical trial data and expert consensus."

Journal • Review • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Renal Disease

Sustained Improvement in Skeletal Dynamics and Renal Function With Palopegteriparatide in Adults With Chronic Hypoparathyroidism: 2-Year Results From the Phase 3 PaTHway Trial (AACE 2025) - P3 | "Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) aims to alleviate hypocalcemia but does not address insufficient PTH. This analysis examines the efficacy and safety of palopegteriparatide treatment in adults with chronic hypoparathyroidism through week 104 of the PaTHway trial (NCT04701203)."

Clinical • P3 data • Endocrine Disorders • Hypoparathyroidism

PaTH Forward: A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism (clinicaltrials.gov) - P2 | N=59 | Completed | Sponsor: Ascendis Pharma A/S | Active, not recruiting ➔ Completed

Trial completion • Endocrine Disorders • Hypoparathyroidism

A CASE WITH SEVERE AND RESISTANT HYPOCALCEMIA AFTER THYROIDECTOMY AND PARATHYROIDECTOMY: UNRAVELING A DIAGNOSTIC ENIGMA (ESPE-ESE 2025) - "Due to persistent hypocalcemia, despite maximal oral conventional treatment and periodic intravenous calcium administration, injectable Palopegteriparatide was initiated resulting to gradual normalization of calcium levels (titration to maximum dose). Additionally, during hospitalization, the patient presented persistent hypokalemia (K =2.9 mmol/l) after the addition of hydrochlorothiazide, which in combination with her past medical history of resistant hypertension and borderline low potassium levels during the last two years, raised the suspicion of primary hyperaldosteronism...Adrenal CT revealed small bilateral adenomas (<10 HU) and spironolactone was added with normalization of both blood pressure and potassium levels... Multiple endocrine neoplasia syndromes are rare diseases, usually familial, caused by mutations in genes related to oncogenesis. A careful review of patient’s medical history and thorough clinical examination are key elements in the diagnostic..."

Clinical • Late-breaking abstract • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Gastrointestinal Disorder • Genetic Disorders • Hypertension • Hypoparathyroidism • Obesity • Oncology • Rare Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Palopegteriparatide use for severe postoperative hypocalcemia (ESPE-ESE 2025) - "Palopegteriparatide can serve as a bridging therapy in patients with severe hypocalcemia due to hypoparathyroidism and HBS after total thyroidectomy for Graves’ disease in the period when satisfactory serum calcium levels cannot be maintained with high doses of calcium and vitamin D supplementation."

Endocrine Disorders • Grave’s Disease • Hypoparathyroidism • Metabolic Disorders • Nephrology • Renal Disease

Preliminary Results from a Prospective Cohort Study on Real-World Data of Chronic Hypoparathyroidism Treated with Trans-Con PTH (ESPE-ESE 2025) - "Background: Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by deficient parathyroid hormone (PTH) levels, leading to hypocalcemia and dependency on calcium and active vitamin D., Trans-conPTH 1-34 formulation (Yorvipath), has emerged as a potential therapeutic option for patients with uncontrolled hypoparathyroidism or those previously treated with rhPTH(1-84)...Additionally, 15 patients (40%) were on hydrochlorothiazide for hypercalciuria... Preliminary findings suggest that Yorvipath is effective in reducing or eliminating the need for calcium and activated vitamin-D treatment in patients with HypoPT. Most patients achieved Ca/active VitD independence within the first few weeks of treatment. Further studies with longer follow-up are warranted to confirm the long-term efficacy and safety of Yorvipath in this patient population."

Clinical • Real-world • Real-world evidence • Endocrine Cancer • Endocrine Disorders • Genetic Disorders • Hypoparathyroidism • Immunology • Metabolic Disorders • Oncology • Sarcoidosis • Solid Tumor • Thyroid Gland Carcinoma

A novel method for the detection of hypercalciuria in individuals with chronic hypoparathyroidism (ESPE-ESE 2025) - P2 | "There were 247 paired ECa/Ccr and 24uCa measurements collected through the 110-week follow-up, including 50 baseline measurements prior to palopegteriparatide initiation. At baseline, median (IQR) 24uCa was 381 (296-602) mg and 72% of individuals had hypercalciuria. Median 24uCa excretion declined to 149, 125, 108, and 150 mg/day during 26, 58, 84, and 110 weeks of open-label period."

Clinical • Endocrine Disorders • Hypoparathyroidism

Palopegteriparatide for the treatment of Autosomal Dominant Hypocalcemia type 1 (ADH1) (ESPE-ESE 2025) - "He was treated with calcium carbonate 500mg 1x2, alfacalcidol 1 mcg 1x1, cholecalciferol 800UI 1x1, hydrochlorothiazide 25mg 1x1, rhPTH (Natpar) 75-100 mcg 1x1 and magnesium supplements. He also received dasatinib for the CML... Until the launch of the calcilytics, palopegteriparatide (Yorvipath) may represent a valuable alternative for the management of ADH1."

Chronic Myeloid Leukemia • Endocrine Disorders • Hematological Malignancies • Hypoparathyroidism • Leukemia • Oncology • CASR

Switch from rhPTH1-84 to TransCon PTH in patients with hypoparathyroidism normalizes phosphate, magnesium metabolism, and bone turnover. (ESPE-ESE 2025) - "Switching treatment from rhPTH1-84 to TransCon PTH was followed by significant changes towards normalization in calcium, phosphate, and magnesium metabolism and bone turnover during the first six months of treatment."

Clinical • Cataract • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Ophthalmology • Rare Diseases • Renal Calculi • Renal Disease • FGF23

Switch from rhPTH1-84 to TransCon PTH with individual Dose Adjustment in Adult Hypoparathyroidism – results for 40 patients one month after treatment transition. (ESPE-ESE 2025) - "Switching treatment from rhPTH1-84 to TransCon PTH using the initial dose of 18 µg proved to be efficient independently of the prior rhPTH1-84 dose. Adverse events were frequent, albeit mild to moderate and no patient withdrew from treatment."

Clinical • CNS Disorders • Endocrine Disorders • Fatigue • Gastrointestinal Disorder • Hypoparathyroidism • Musculoskeletal Pain • Pain • Sleep Disorder

Long-Term Efficacy and Safety of Palopegteriparatide Treatment in Adults With Chronic Hypoparathyroidism: 4-Year Results From the Phase 2 PaTH Forward Trial (ESPE-ESE 2025) - "TEAEs were mostly mild or moderate; no new safety signals were identified. Conclusion These results demonstrate sustained efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of the PaTH Forward trial, highlighting continued benefits in skeletal dynamics and renal function."

Clinical • P2 data • Endocrine Disorders • Hypoparathyroidism

Palopegteriparatide (Yorvipath) for hypoparathyroidism. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Endocrine Disorders • Hypoparathyroidism

The calcium-sensing receptor: a comprehensive review on its role in calcium homeostasis and therapeutic implications. (PubMed, Am J Transl Res) - "Current pharmacological agents, including calcimimetics such as cinacalcet and etelcalcetide, have proven effective in managing secondary hyperparathyroidism (SHPT); however, they are associated with side effects such as hypocalcemia. Emerging investigational drugs, including palopegteriparatide and other small molecules, show promise in addressing various calcium-related conditions. Despite challenges that have led to the discontinuation of some drug developments, ongoing research is focused on refining CaSR-targeted therapies to improve efficacy, reduce adverse effects, and enhance patient outcomes."

Journal • Review • Endocrine Disorders • Hypoparathyroidism • Secondary Hyperparathyroidism

2024 FDA TIDES (Peptides and Oligonucleotides) Harvest. (PubMed, Pharmaceuticals (Basel)) - "Interestingly, among the strategies employed in recent approvals to enhance stability and/or delivery, the prodrug approach, exemplified by palopegteriparatide and pegulicianine, is emerging as a more targeted and precise therapeutic strategy. Additionally, the Enhanced Stabilization Chemistry (ESC)-GalNAc platform has been expanded for hepatic delivery of a new oligonucleotide drug, olezarsen. Furthermore, novel modifications to the ribose moiety in oligonucleotides, such as the 3'-amino substitution in imetelstat, enhance their stability. This review examines the TIDES approved in 2024 based on their chemical structure, medical targets, modes of action, administration routes, and common adverse effects. In addition, it highlights how the prodrug strategy has improved targeting efficiency and extended the half-lives of the active drugs."

Journal • Review • Developmental Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders