Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Clarke BL, Khan AA, Rubin MR, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. Epub 2024 Oct 8; doi: 10.1210/clinem/dgae693. PMID: 39376010.
  • Background:
    • Parathyroid hormone (PTH) serves to maintain calcium phosphate homeostasis:
      • Through its actions on bone, kidney, and the intestines
    • Hypoparathyroidism occurs at an incidence of:
      • 0.8 to 2.6 per 100,000 person-years:
        • With postsurgical hypoparathyroidism being the most common etiology
    • Patients with chronic hypoparathyroidism conventionally have been treated with:
      • Activated vitamin D and oral calcium supplementation to maintain normal calcium levels:
        • They can experience cognitive impairment, renal complications, and extraskeletal calcification
    • PTH replacement therapy:
      • Is of interest to restore normal physiology while mitigating pill burden and complications from conventional treatments of chronic hypoparathyroidism
    • The PaTHway trial:
      • Is an ongoing phase 3 clinical trial of TransCon PTH, or palopegteriparatide:
        • Which is a subcutaneously administered prodrug of PTH (1,23):
          • That releases a sustained level of active PTH over 24 hours, allowing patients with hypoparathyroidism the ability to achieve physiologic levels of active PTH
      • Data from the first 26 weeks of the PaTHway trial, in which 82 enrolled adult patients with chronic hypoparathyroidism were randomly assigned to receive either TransCon PTH or placebo in a double-blind, placebo-controlled clinical trial have previously been reported
      • In the first 26 weeks of this trial, patients were found to have normalization of calcium levels of conventional treatments for hypoparathyroidism and improved health-related quality of life
      • The current publication presents the longer-term outcomes of this trial
  • Methods:
    • In the present study, Clarke et al. present the results of the PaTHway trial at 52 weeks of follow-up
    • After the first 26 weeks of the trial, patients were eligible to a 156-week open-label extension (OLE) during which they received dose-adjusted TransCon PTH
    • The primary outcome remained independence from conventional treatment, defined as achieving albumin-corrected calcium in the normal range while not taking activated vitamin D or therapeutic doses of calcium (≤ 600 mg) on the day before the patient’s visit
    • The authors also tracked patient-reported outcomes using the Hypoparathyroidism Patient Experience Scale (HPES) and the 36-Item Short-Form Health Survey (SF-36)
    • The authors assessed longer-term outcomes of patients who were treated with TransCon PTH at baseline and compared results of the patients who were on placebo from baseline to 26 weeks and transitioned to receiving TransCon PTH at 26 weeks when they entered the OLE phase of the trial to patients who were treated with TransCon PTH from the start of the study
  • Results:
    • There were 79 participants (60 taking TransCon PTH and 19 placebo) of the initial 82 participants (61 TransCon PTH, 21 placebo) enrolled in the study who completed the first 26-week blinded treatment and entered the OLE:
      • 78 patients completed 52 weeks of the trial (59 TransCon PTH, 19 placebo)
    • The majority of participants enrolled had postsurgical hypoparathyroidism (70 of 82 [85%]) with a mean (±SD) duration of hypoparathyroidism of 11.7±10.7 years
    • Of the 78 participants who received TransCon PTH and completed 52 weeks of the trial, 74 (98%) achieved independence from conventional treatment
    • Patients who were randomly assigned to TransCon PTH at the initiation of the trial had significant improvement in HPES hypoparathyroidism-related symptoms, functioning, and well-being throughout the duration of the trial
    • Patients on placebo at baseline who received TransCon PTH in the OLE at 26 weeks noted similar improvements in HPES score after initiation of TransCon PTH
    • Similar improvements were noted in SF-36 scores
    • Of the 80 patients who received TransCon PTH, 42 (53%) reported treatment-emergent adverse events, which included injection-site reaction (21 patients), nausea (7), headache (6), and hypocalcemia (4) and two serious adverse events related to hypercalcemia that resolved with supportive therapy; all episodes of hypercalcemia were in the first 90 days of treatment and were thought to be related to titration of TransCon PTH dosing
  • Conclusions:
    • TransCon PTH is a promising treatment for chronic hypoparathyroidism that can sustain normal calcium levels with daily dosing and mitigate symptoms that impact patient quality of life with minimal risk
  • Hypoparathyroidism is the most common complication after thyroidectomy:
    • With rates of permanent hypoparathyroidism ranging from 0.5% to 14.5%
  • Although patients with permanent hypoparathyroidism can maintain normal serum calcium levels with activated vitamin D supplementation and / or calcium supplementation, the long-term alteration in PTH physiology and need for calcitriol or calcium can negatively impact patients’ renal function, result in extraskeletal calcification, and result in symptoms that impact their quality of life
  • Clarke et al.’s findings present a promising PTH replacement for patients who experience permanent hypoparathyroidism
  • In the perioperative setting, both patients and surgeons are often most worried about voice changes and the potential for immediate life-threatening complications, such as postoperative hematoma
  • Recent advances in thyroid surgery have allowed for the rates of postoperative recurrent laryngeal nerve injury and postoperative hematoma that necessitate emergent reoperation to be rare occurrences when thyroidectomy is performed by a high-volume thyroid surgeon
  • Although permanent hypoparathyroidism after parathyroidectomy does not immediate threaten a patient’s life, it is a chronic health problem for which there has not been a promising therapeutic treatment to addresses the underlaying deficiency in PTH
  • With the data of the PaTHway trial demonstrating stable calcium levels and improved patient-reported outcomes once a physiologic dose is achieved, TransCon PTH treatment may enable more routine care along with thyroid hormone replacement at postoperative visits
  • Every effort must still be made to preserve parathyroid function, including performing autotransplantation when appropriate; however, TransCon PTH is an encouraging treatment for postoperative hypoparathyroidism
  • Key points:
    • In this open-label extension trial of the parathyroid hormone analogue TransCon PTH, palopegteriparatide, for the treatment of hypoparathyroidism, patients initially enrolled in a 26-week randomized controlled trial either continued or were switched to, TransCon PTH
    • Of TransCon PTH–treated participants who completed 52 weeks of the trial, 98% achieved independence from oral treatments
    • Subjects initially randomly assigned to TransCon PTH maintained a quality-of-life benefit throughout the trial, while those switched to TransCon PTH from placebo showed improved symptoms scores after this change
    • These findings provide encouraging data for TransCon PTH treatment for postoperative hypoparathyroidism to reduce dependence on oral supplementation and improve side effects with acceptable adverse effects
  • References:
    • Clarke BL. Epidemiology and complications of hypoparathyroidism. Endocrinol Metab Clin North Am 2018;47(4):771-782.
    • Khan AA, Rubin MR, Schwarz P, et al. Efficacy and safety of parathyroid hormone replacement with TransCon PTH in hypoparathyroidism: 26-week results from the phase 3 PaTHway Trial. J Bone Miner Res 2023;38(1):14-25.
    • Clarke BL, Khan AA, Rubin MR, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. Epub 2024 Oct 8.
    • Niu A, Zhou L, Papachristos A, et al. Permanent hypoparathyroidism following total thyroidectomy—incidence and preventative strategies without imaging adjuncts. Am J Surg 2025;116196.
Unknown's avatar

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

Leave a comment