Study: Yorvipath replaces calcium supplements, vitamin D for most
Early access program provided treatment to group ahead of its approval
A new study shows that Yorvipath (palopegteriparatide), a hormone replacement therapy, eliminates the need for conventional calcium and active vitamin D supplements in most adults with hypoparathyroidism. The therapy achieves this while keeping blood calcium levels stable and within the normal range.
These findings come from a U.S. expanded access program (EAP), which provided early access to the therapy before its official approval. Unlike its Phase 3 PaTHway trial (NCT04701203), the program allowed the enrollment of people who were switching directly from another hormone replacement therapy. No new safety concerns arose up to a year of treatment in the EAP.
“This real-world study provides early evidence to support the use of [Yorvipath] for the treatment of adults with hypoparathyroidism,” the researchers wrote. “These results are consistent with the safety and efficacy profile that was established in the PaTHway clinical trial, including rapid and sustained reduction of conventional therapy.”
The study, “Early US Real-World Treatment Patterns and Outcomes in Palopegteriparatide Treatment for Patients with Hypoparathyroidism,” was published in Endocrine Practice.
Conventional therapy and its long-term risks
Conventional treatment for hypoparathyroidism relies on daily supplements — calcium and calcitriol (an active form of vitamin D) — to correct low calcium levels caused by parathyroid hormone (PTH) deficiency. While these can ease symptoms, they do not replace the missing hormone, and long-term use raises the risk of kidney problems.
Yorvipath, marketed by Ascendis Pharma and previously known as Transcon PTH, is given by once-daily injection to deliver a steady supply of PTH, helping restore calcium balance. It has been approved in the U.S., European Union, and elsewhere for adults with hypoparathyroidism, supported in part by efficacy and safety results from the PaTHway trial.
Until recently, the only PTH replacement approved in the U.S. was Takeda’s Natpara. That medication was recalled in 2019 and permanently discontinued worldwide at the end of 2024.
Launched in 2023, the EAP helped bridge this treatment gap, giving people early access to treatment while collecting real-world outcomes.
Researchers in the U.S. analyzed data from 123 adults with hypoparathyroidism treated with Yorvipath through the EAP across 60 sites nationwide. Most participants were women (93.5%), younger than 65 (82.1%), and diagnosed with post-surgical hypoparathyroidism (82.1%). Nearly all (95.1%) had previously used short-acting PTH therapies, most often Natpara (69.1%).
Slightly more than half (50.4%) were “direct switch,” meaning they transitioned to Yorvipath within one day after stopping a prior PTH therapy. The remaining 49.6% were nondirect switch, meaning they had a gap of two or more days between therapies or weren’t previously on any PTH therapy.
The two groups were generally similar in age, sex, and disease history. Direct switch patients had been living with hypoparathyroidism slightly longer (median 12.8 vs. 10.8 years) and were less likely to be using conventional supplements at the study’s start.
Across both groups, the median exposure to Yorvipath was 5.2 months. The median dose was 18 micrograms per day at three months and 21 micrograms a day by one year (in patients with available data). Overall, dosing was consistent between groups.
Yorvipath achieves independence from supplements
By one year, all direct-switch participants were able to stop conventional therapy altogether — just more than half of them (51.8%) used calcium or calcitriol when the study began. Among non-direct switch participants, most had also stopped standard therapy by one year. In both groups, the use of calcium and calcitriol supplements dropped within the first three months.
Blood calcium levels remained stable and within the normal range in both groups, regardless of prior treatment history.
Yorvipath was generally well tolerated. Treatment-related adverse events were reported in 56 people (45.5%) and were mostly mild or moderate. The most common were episodes of low or high calcium, usually within the first 90 days of treatment. Nine people developed serious side effects, including episodes of low calcium or low potassium.
Three people (2.4%) stopped treatment due to side effects, and no one discontinued due to lack of effectiveness.
Finally, in two cases where prior PTH therapy briefly overlapped with Yorvipath during the transition, patients maintained stable calcium levels.
“Findings from the EAP demonstrate that [Yorvipath] is safe and effective in a real-world setting across a broad patient population with hypoparathyroidism, including those ineligible for clinical trials,” the researchers wrote. “These findings are consistent with the overall efficacy and safety of the pivotal phase 3 PaTHway trial.”
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