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

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TransCon PTH, a long-acting PTH, in patients with hypoparathyroidism: Results of the phase 2 PaTH forward trial

Tanja Sikjaer1, Lars Rejnmark1, Aliya Khan2, Peter Schwarz3, Tamara Vokes4, Bart Clarke5, Mishaela Rubin6, Lorenz Hofbauer7, Erik Eriksen8, Andrea Palermo9, Uberto Pagotto10, Claudio Marcocci11, Intekhab Ahmed12, Sanchita Mourya13, Denka Markova13 & David B Karpf13


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

Prague, Czech Republic
23 May 2020 - 26 Feb 2020

European Society of Endocrinology 

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