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Endocrine Abstracts (2020) 70 OC6.5 | DOI: 10.1530/endoabs.70.OC6.5

1Aarhus University Hospital, Aarhus, Denmark; 2Bone Research & Education Center, Oakville, Canada; 3Rigshospitalet, Copenhagen, Denmark; 4University of Chicago, Chicago, United States; 5Mayo Clinic, Rochester, United States; 6Colombia University, New York, United States; 7Universitätsklinikum Dresden, Dresden, Germany; 8Oslo University Hospial, Institue of Clinical Medicine, Oslo, Norway; 9Campus Bio-Medico University, Rome, Italy; 10Alma Mater Studiorum University of Bologna, Balogna, Italy; 11University of Pisa, Pisa, Italy; 12Thomas Jefferson University, Philadelphia, United States; 13Ascendis Pharma Inc., Palo Alto, United States


Background: Hypoparathyroidism (HP) is characterized by low serum calcium (sCa) and high serum phosphate (sP). Standard of care (SoC), active vitamin D and calcium, raises sCa and sP and increases burden of illness on HP patients by worsening hypercalciuria and the CaxP product. Parathyroid hormone (PTH)(1–84)(t1/2 ~2–3 hrs) is approved and can raise sCa and allow partial withdrawal of SoC, but does not sufficiently control urine calcium or symptomatic hypo- or hypercalcemia. [NATPARA Package Insert; Khurana M et al. 2019] TransCon PTH, an investigational prodrug of PTH(1–34) transiently bound to an inert carrier via a linker, is under development for the treatment of HP. Linker auto-cleavage occurs under physiologic conditions, releasing active PTH at a controlled rate with a t1/2 ~60 hrs.

Methods: PaTH Forward is a phase 2, double-blind, placebo-controlled trial evaluating TransCon PTH in adult HP patients treated with SoC. Subjects received fixed-dose TransCon PTH 15, 18, or 21 µg/day or placebo for 4 weeks, followed by an open-label extension period during which subjects could titrate their individual TransCon PTH dose (6–30 µg/day). The primary composite endpoint at Week 4 required 1) normal sCa, 2) normal (or ≥50% decrease from baseline) fractional excretion of calcium (FECa), 3) not taking active vitamin D, and 4) taking ≤1000 mg/day of calcium.

Results: At Week 4, significantly more subjects (50%) on TransCon PTH achieved the primary endpoint vs (15%) subjects on placebo (Table). sP decreased from baseline by 20% in subjects on TransCon PTH vs 1% on placebo. Increase from baseline in subjects meeting FECa endpoint was 42% on TransCon PTH vs 0% on placebo. Free PTH showed stable levels in the lower half of the normal range at both 2 and 4 weeks. TransCon PTH was well-tolerated; no subjects discontinued treatment or withdrew from the trial during the 4-week period, and no SAEs or severe AEs were reported. No subjects on TransCon PTH showed symptomatic hypocalcemia vs 7% on placebo.

Conclusions: Results from the initial 4 weeks of the PaTH Forward Trial demonstrated the TransCon PTH met the primary endpoint without increased incidence of symptomatic hypocalcemia despite a fixed dose. This trial will help inform the starting dose and SoC titration schedule for the phase 3 trial.

Week 4
TransCon PTH (n = 44)Placebo (n = 13)P-value
Off active vitamin D and ≤ 500 mg/day calcium82%15%P < 0.0001
Off active vitamin D and calcium50%0%P = 0.0008
Primary Endpoint50%15%P = 0.0305

Volume 70

22nd European Congress of Endocrinology

Online
05 Sep 2020 - 09 Sep 2020

European Society of Endocrinology 

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