Yorvipath for chronic hypoparathyroidism, addressing limited trt options

Medical experts draw attention to hormone replacement therapy…”Raising disease awareness is urgent”

Overcoming the prior limitation in taking high-dose calcium and vitamin D

Product photo of Yorvipath

There is an urgent need to raise social and medical awareness of chronic hypoparathyroidism, a rare disease caused by parathyroid hormone (PTH) deficiency.

The recent emergence of Yorvipath (palopegteriparatide), an innovative drug that directly replaces parathyroid hormone, is driving a paradigm shift in treatment for patients who previously relied solely on high-dose calcium supplements and active vitamin D due to the lack of disease-modifying therapies. The need to improve disease awareness is also being highlighted.

Developed by Denmark-based Ascendis Pharma, Yorvipath obtained marketing approvals in Europe in 2023, the U.S. in 2024, and Japan in 2025, and subsequently obtained orphan drug designation in South Korea for the active ingredient palopegteriparatide this past March.

Currently, Kolon Pharma, which entered into an exclusive domestic distribution agreement with Ascendis Pharma, submitted a marketing authorization application to the Ministry of Food and Drug Safety (MFDS) in May, and as of the 4th, Yorvipath is undergoing the MFDS approval review process.

Chronic hypoparathyroidism is a rare condition that often suffers from a lack of awareness about the disease, leaving patient diagnosis and treatment in a blind spot. Chronic hypoparathyroidism is a rare endocrine disorder where deficient secretion or impaired function of parathyroid hormone (PTH) leads to severe hypocalcemia and hyperphosphatemia.

Patients suffer from various physical and mental symptoms, including numbness and tingling in the extremities, muscle cramps, tetany, extreme fatigue, and cognitive impairment. However, low awareness of the disease among both the public and healthcare professionals often leads to initial symptoms being dismissed as simple fatigue, eye twitching, or nutritional imbalance, failing to lead to proper specialized diagnosis.

Medical experts advise, "If left untreated, chronic hypoparathyroidism can progress to life-threatening severe hypocalcemic crises or chronic complications, making proactive outreach and heightened disease awareness a priority."

Until now, the standard of care for chronic hypoparathyroidism has involved daily administration of active vitamin D and high-dose calcium supplements. However, these symptomatic treatments fail to replace the deficient PTH hormone itself and impose a heavy pill burden on severe patients, who must ingest dozens of calcium and active vitamin D tablets daily.

A greater issue involves long-term complications. While administering excessive calcium and active vitamin D under PTH-deficient conditions may temporarily maintain serum calcium levels, it fails to restore PTH's role in regulating renal calcium reabsorption, potentially leading to hypercalciuria (excessive urinary calcium excretion). If persistent, this significantly elevates the risk of severe secondary renal damage, including nephrolithiasis, nephrocalcinosis, and chronic kidney disease (CKD).

Disease-modifying drug Yorvipath, a paradigm shift via 24-hour physiological hormone replacement

Yorvipath, developed by global biopharmaceutical company Ascendis Pharma, has been evaluated as opening a new era in the treatment of chronic hypoparathyroidism.

Yorvipath is a PTH replacement therapy engineered to continuously provide active PTH(1-34) within physiological ranges over 24 hours. Administered once daily via subcutaneous injection, it is designed to physiologically address the underlying PTH deficiency, the underlying cause of hypoparathyroidism, by maintaining continuous systemic exposure to active PTH.

In the pivotal global Phase 3 PaTHway trial, a randomized, double-blind, placebo-controlled study in adult patients with chronic hypoparathyroidism, 79% (48/61) of patients in the Yorvipath arm met the primary composite endpoint at 26 weeks, maintaining albumin-adjusted serum calcium within normal ranges and maintaining a stable Yorvipath dose while achieving independence from conventional therapy. Furthermore, 93% (57/61) of Yorvipath-treated patients achieved independence from conventional calcium and active vitamin D therapy.

Additionally, the Yorvipath group demonstrated improvements in estimated glomerular filtration rate (eGFR) from baseline and achieved normalization of mean 24-hour urinary calcium excretion levels (250 mg/day or lower). This suggests the potential to substantially reduce the risk of nephrocalcinosis and progression to chronic kidney disease, which remain major concerns under conventional care.

Moreover, assessments using the Hypoparathyroidism Patient Experience Scale (HPES) demonstrated significant reductions in physical symptom burden alongside marked improvements in overall quality of life.

To date, Chronic hypoparathyroidism has been a neglected disease where patients had to ingest large amounts of calcium supplements at the risk of renal complications due to the absence of hormone replacement therapy. As Yorvipath has demonstrated clinical efficacy and safety, calls to raise disease awareness and prioritize public health policy support are growing.

Healthcare experts stress that to ensure patients with chronic hypoparathyroidism receive timely, accurate diagnoses and benefit from advanced hormone replacement therapies like Yorvipath, efforts must concurrently focus on ▲public and primary care disease awareness campaigns, ▲dissemination of accurate diagnostic guidelines, and ▲institutional support to enhance treatment access.

A representative from Kolon Pharma stated, "Chronic hypoparathyroidism has represented a major unmet medical need where patients had no choice but to manage symptoms via calcium and active vitamin D supplementation due to the lack of hormone replacement therapy directly treating the root cause of PTH deficiency," and added, "We will do our utmost to secure marketing authorization and reimbursement for palopegteriparatide inj so that it can be supplied to patients as swiftly as possible."