Palopegteriparatide

Yorvipath , FDA 2024, 8/9/2024, To treat hypoparathyroidism

• G2N64C3385
• 2222514-07-8
• Palopegteriparatide
• UNII-G2N64C3385
• ACP-014
• Mpeg 40000-teriparatide
• Palopegteriparatide [INN]
• Transcon parathyroid hormone (1-34)
• Transcon pth (1-34)
• Palopegteriparatide [USAN]
• TransCon PTH
• WHO 11060

Palopegteriparatide Palopegteriparatide is a human parathyroid hormone analogue corresponding to amino acid residues 1 – 34 of human parathyroid hormone, to which a methoxy polyethylene glycol (molecular weight: ca. 43,000) is bound via a cleavable linker (pegylation site: S1). Palopegteriparatide is a pegylated synthetic peptide (molecular weight: ca. 48,000) consisting of 34 amino acid residues. [2222514-07-8]

Palopegteriparatide, sold under the brand name Yorvipath, is a hormone replacement therapy used for the treatment of hypoparathyroidism.^[1][2] It is a transiently pegylated parathyroid hormone.^[4] It is a parathyroid hormone analog.^[1]

Palopegteriparatide was approved for medical use in the European Union in November 2023,^[2] and in the United States in August 2024.^[1][5]

Medical uses

Palopegteriparatide is indicated for the treatment of adults with hypoparathyroidism.^[1][2]

Adverse effects

The US Food and Drug Administration (FDA) prescription label for palopegteriparatide includes warnings for a potential risk of risk of unintended changes in serum calcium levels related to number of daily injections and total delivered dose, serious hypocalcemia and hypercalcemia (blood calcium levels that are too high), osteosarcoma (a rare bone cancer) based on findings in rats, orthostatic hypotension (dizziness when standing), and a risk of a drug interaction with digoxin (a medicine for certain heart conditions).^[5]

History

The effectiveness of palopegteriparatide was evaluated in a 26-week, randomized, double-blind, placebo-controlled trial that enrolled 82 adults with hypoparathyroidism.^[5] Prior to randomization, all participants underwent an approximate four-week screening period in which calcium and active vitamin D supplements were adjusted to achieve an albumin-corrected serum calcium concentration between 7.8 and 10.6 mg/dL, a magnesium concentration ≥1.3 mg/dL and below the upper limit of the reference range, and a 25(OH) vitamin D concentration between 20 to 80 ng/mL.^[5] During the double-blind period, participants were randomized to either palopegteriparatide (N = 61) or placebo (N= 21), at a starting dose of 18 mcg/day, co-administered with conventional therapy (calcium and active vitamin D).^[5] Study drug and conventional therapy were subsequently adjusted according to the albumin-corrected serum calcium levels.^[5] At the end of the trial, 69% of the participants in the palopegteriparatide group compared to 5% of the participants in the placebo group were able to maintain their calcium level in the normal range, without needing active vitamin D and high doses of calcium (calcium dose ≤ 600 mg/day).^[5]

The FDA granted the application for palopegteriparatide orphan drug and priority review designations.^[5]

Society and culture

Legal status

In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yorvipath, intended for the treatment of chronic hypoparathyroidism in adults.^[4][6] The applicant for this medicinal product is Ascendis Pharma Bone Diseases A/S.^[4] Palopegteriparatide was approved for medical use in the European Union in November 2023.^[2]

Palopegteriparatide was granted an orphan drug designation by the US Food and Drug Administration (FDA) in 2018,^[7] and by the EMA in 2020.^[8]

Brand names

Palopegteriparatide is the international nonproprietary name.^[9][10]

Palopegteriparatide is sold under the brand name Yorvipath.^[2]

References

1. ^ Jump up to:^{a b c d e} “Yorvipath injection, solution”. DailyMed. 14 August 2024. Retrieved 5 September 2024.
2. ^ Jump up to:^{a b c d e f} “Yorvipath EPAR”. European Medicines Agency. 19 October 2020. Archived from the original on 10 December 2023. Retrieved 11 December 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
3. ^ “Yorvipath Product information”. Union Register of medicinal products. 20 November 2023. Archived from the original on 26 November 2023. Retrieved 11 December 2023.
4. ^ Jump up to:^a b c “Yorvipath: Pending EC decision”. European Medicines Agency. 15 September 2023. Archived from the original on 24 September 2023. Retrieved 24 September 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
5. ^ Jump up to:^{a b c d e f g h} “FDA approves new drug for hypoparathyroidism, a rare disorder”. U.S. Food and Drug Administration (FDA) (Press release). 9 August 2024. Archived from the original on 13 August 2024. Retrieved 13 August 2024.  This article incorporates text from this source, which is in the public domain.
6. ^ “Ascendis Pharma Receives Positive CHMP Opinion for TransCon PTH (palopegteriparatide) for Adults with Chronic Hypoparathyroidism”. Ascendis Pharma (Press release). 14 September 2023. Archived from the original on 24 September 2023. Retrieved 24 September 2023.
7. ^ “TransCon Parathyroid Hormone (mPEG conjugated parathyroid hormone 1-34) Orphan Drug Designations and Approvals”. U.S. Food and Drug Administration (FDA). Archived from the original on 24 September 2023. Retrieved 24 September 2023.
8. ^ “EU/3/20/2350”. European Medicines Agency. 15 September 2023. Archived from the original on 24 September 2023. Retrieved 24 September 2023.
9. ^ World Health Organization (2021). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 86”. WHO Drug Information. 35 (3). hdl:10665/346562.
10. ^ World Health Organization (2023). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89”. WHO Drug Information. 37 (1). hdl:10665/366661.

External links

• Palopegteriparatide Global Substance Registration System
• Palopegteriparatide NCI Thesaurus
• Clinical trial number NCT04701203 for “A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism (PaTHway)” at ClinicalTrials.gov

Clinical data
Trade names	Yorvipath
Other names	ACP-014, TransCon PTH
License data	US DailyMed: Palopegteriparatide
Routes of administration	Subcutaneous
Drug class	Hormonal agent
ATC code	H05AA05 (WHO)
Legal status
Legal status	US: ℞-only[1]EU: Rx-only[2][3]
Identifiers
CAS Number	2222514-07-8
UNII	G2N64C3385
KEGG	D12395

//////Palopegteriparatide, APPRoVALS 2024, FDA 2024, Yorvipath, hypoparathyroidism, UNII-G2N64C3385, ACP-014, TransCon PTH, WHO 11060