Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial

Bart L Clarke; Aliya A Khan; Mishaela R Rubin; Peter Schwarz; Tamara Vokes; Dolores M Shoback; Claudia Gagnon; Andrea Palermo; Lisa G Abbott; Lorenz C Hofbauer; Lynn Kohlmeier; Filomena Cetani; Susanne Pihl; Xuebei An; Alden R Smith; Bryant Lai; Jenny Ukena; Christopher T Sibley; Aimee D Shu; Lars Rejnmark

doi:10.1210/clinem/dgae693

Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial

Bart L Clarke, Aliya A Khan, Mishaela R Rubin, Peter Schwarz, Tamara Vokes, Dolores M Shoback, Claudia Gagnon, Andrea Palermo, Lisa G Abbott, Lorenz C Hofbauer, Lynn Kohlmeier, Filomena Cetani, Susanne Pihl, Xuebei An, Alden R Smith, Bryant Lai, Jenny Ukena, Christopher T Sibley, Aimee D Shu^*, Lars Rejnmark

^*Corresponding author af dette arbejde

Afdeling for Nyre- og Hormonsygdomme

Abstract

CONTEXT: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels.

OBJECTIVE: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism.

DESIGN: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE).

SETTING: 21 sites across North America and Europe.

PARTICIPANTS: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52.

INTERVENTION(S): All OLE participants received TransCon PTH administered once daily.

MAIN OUTCOME MEASURE(S): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs).

RESULTS: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE.

CONCLUSIONS: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

Originalsprog	Engelsk
Tidsskrift	The Journal of clinical endocrinology and metabolism
ISSN	0021-972X
DOI	https://doi.org/10.1210/clinem/dgae693
Status	E-pub ahead of print - 8 okt. 2024

Adgang til dokumentet

10.1210/clinem/dgae693

Citationsformater

Clarke, B. L., Khan, A. A., Rubin, M. R., Schwarz, P., Vokes, T., Shoback, D. M., Gagnon, C., Palermo, A., Abbott, L. G., Hofbauer, L. C., Kohlmeier, L., Cetani, F., Pihl, S., An, X., Smith, A. R., Lai, B., Ukena, J., Sibley, C. T., Shu, A. D., & Rejnmark, L. (2024). Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial. The Journal of clinical endocrinology and metabolism. Advance online publication. https://doi.org/10.1210/clinem/dgae693

Clarke, BL, Khan, AA, Rubin, MR, Schwarz, P, Vokes, T, Shoback, DM, Gagnon, C, Palermo, A, Abbott, LG, Hofbauer, LC, Kohlmeier, L, Cetani, F, Pihl, S, An, X, Smith, AR, Lai, B, Ukena, J, Sibley, CT, Shu, AD & Rejnmark, L 2024, 'Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial', The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/clinem/dgae693

@article{3c3744fa2ad54ad484613cb1c10e08ca,

title = "Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial",

abstract = "CONTEXT: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels.OBJECTIVE: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism.DESIGN: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE).SETTING: 21 sites across North America and Europe.PARTICIPANTS: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52.INTERVENTION(S): All OLE participants received TransCon PTH administered once daily.MAIN OUTCOME MEASURE(S): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs).RESULTS: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE.CONCLUSIONS: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.",

author = "Clarke, {Bart L} and Khan, {Aliya A} and Rubin, {Mishaela R} and Peter Schwarz and Tamara Vokes and Shoback, {Dolores M} and Claudia Gagnon and Andrea Palermo and Abbott, {Lisa G} and Hofbauer, {Lorenz C} and Lynn Kohlmeier and Filomena Cetani and Susanne Pihl and Xuebei An and Smith, {Alden R} and Bryant Lai and Jenny Ukena and Sibley, {Christopher T} and Shu, {Aimee D} and Lars Rejnmark",

note = "{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.",

year = "2024",

month = oct,

day = "8",

doi = "10.1210/clinem/dgae693",

language = "English",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "The/Endocrine Society",

}

TY - JOUR

T1 - Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism

T2 - 52-Week Results From the Phase 3 PaTHway Trial

AU - Clarke, Bart L

AU - Khan, Aliya A

AU - Rubin, Mishaela R

AU - Schwarz, Peter

AU - Vokes, Tamara

AU - Shoback, Dolores M

AU - Gagnon, Claudia

AU - Palermo, Andrea

AU - Abbott, Lisa G

AU - Hofbauer, Lorenz C

AU - Kohlmeier, Lynn

AU - Cetani, Filomena

AU - Pihl, Susanne

AU - An, Xuebei

AU - Smith, Alden R

AU - Lai, Bryant

AU - Ukena, Jenny

AU - Sibley, Christopher T

AU - Shu, Aimee D

AU - Rejnmark, Lars

PY - 2024/10/8

Y1 - 2024/10/8

N2 - CONTEXT: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels.OBJECTIVE: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism.DESIGN: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE).SETTING: 21 sites across North America and Europe.PARTICIPANTS: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52.INTERVENTION(S): All OLE participants received TransCon PTH administered once daily.MAIN OUTCOME MEASURE(S): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs).RESULTS: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE.CONCLUSIONS: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

AB - CONTEXT: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels.OBJECTIVE: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism.DESIGN: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE).SETTING: 21 sites across North America and Europe.PARTICIPANTS: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52.INTERVENTION(S): All OLE participants received TransCon PTH administered once daily.MAIN OUTCOME MEASURE(S): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs).RESULTS: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE.CONCLUSIONS: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

U2 - 10.1210/clinem/dgae693

DO - 10.1210/clinem/dgae693

M3 - Journal article

C2 - 39376010

SN - 0021-972X

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

ER -

Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater