Daily use of hypoparathyroidism drug leads to rapid gains in kidney health
New trial data show patients on Yorvipath also stopping supplements
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Daily treatment with Yorvipath (palopegteriparatide) leads to rapid and sustained improvement in kidney function among adults with hypoparathyroidism, according to newly published data from the PaTHway trial, whose earlier results were used to back the drug’s widespread approvals.
Gains in kidney health for these patients were seen regardless of whether their kidney function was impaired or preserved at the start of the Phase 3 trial, which wrapped up last year, the researchers noted.
Additionally, blood calcium levels normalized in most study participants, with all either stopping or reducing daily calcium and vitamin D supplementation, the full data show.
“The results suggest that [Yorvipath] treatment may help preserve or improve kidney function in adults with chronic hypoparathyroidism,” the researchers wrote, noting also that “no new safety signals were identified” in the trial’s second half.
The study, “Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway-trial,” was published in the Journal of Bone and Mineral Research. Six of the 23 study authors worked for Ascendis Pharma, the therapy’s developer, which also funded the work.
In hypoparathyroidism, the parathyroid glands produce too little parathyroid hormone (PTH), which is critical for regulating calcium and phosphorus levels in the body. People with this condition are typically managed with conventional therapy — active vitamin D and calcium supplements — but that approach carries risks for the kidneys over time.
Treatment’s approval based on PaTHway, PaTH Forward trial data
Yorvipath is a PTH replacement therapy approved in the U.S., the European Union, Australia, Japan, and several other regions. Given as a once-daily injection under the skin, or subcutaneously, the therapy is designed to raise PTH levels in the bloodstream to help normalize calcium levels.
Data from two clinical trials supported Yorvipath’s approval; the treatment won regulatory clearance in the U.S. in 2024 and was granted marketing authorization in the EU in late 2023.
In the Phase 2 PaTH Forward trial (NCT04009291), participants received Yorvipath or a placebo for four weeks, then were given the then experimental therapy for up to about five years. In PaTHway (NCT04701203), a late-stage trial, participants received the therapy or a placebo for about six months, followed by Yorvipath for about three years.
Some data from both trials, presented at last year’s annual meeting of the American Society for Nephrology, showed that Yorvipath improved kidney function in adults with hypoparathyroidism within months of starting treatment. Those benefits were sustained for at least three years, the data showed.
Researchers have now published full details of the PaTHway trial, which enrolled 82 adults with hypoparathyroidism. Most (85%) had developed the condition as a result of neck surgery. Slightly more than one-quarter had impaired kidney function at the study’s start, as indicated by a lower estimated glomerular filtration rate (eGFR).
Participants were randomly assigned to receive Yorvipath or placebo by once-daily injection for the study’s first 26 weeks, or about six months, alongside their conventional therapy — specifically, calcium and active vitamin D supplements. Thereafter, those who had been on the placebo were switched to Yorvipath, and all continued on the drug through week 104, or the two-year mark.
By week 104, nearly all participants (93%) remained in the study. Of those, 80% achieved normal blood calcium levels and were independent of conventional therapy, the data show.
Importantly, 100% of the participants had stopped active vitamin D entirely, and 97% had reduced calcium supplementation to 600 mg per day or less. Most (82%) maintained blood calcium within the normal range. Blood phosphate and the calcium-phosphate product, a combined measure relevant to kidney and vascular health, were also within normal ranges at week 104.
Kidney function improved for all trial participants
Kidney function was tracked with eGFR, measured in milliliters of blood per minute per 1.73 square meters of kidney tissue (mL/min/1.73 m2).
It improved significantly with Yorvipath treatment, according to the data, which showed that, across all participants, the mean eGFR rose by 8.9 mL/min/1.73 m2 by one year and remained elevated through week 104. By week 104, 45% had an increase in eGFR of 5 mL/min/1.73 m2, and 34% had an increase of 10 mL/min/1.73 m2 or more.
Among those who began the study with reduced kidney function, by week 104, 78% achieved an increase in eGFR of 5 or more mL/min/1.73 m2, and 57% achieved an increase of 10 or more mL/min/1.73 m2. And, the proportion of participants with an eGFR lower than 60 mL/min/1.73 m2 fell from 28% to 9%.
No participants experienced a sustained decrease in eGFR of 30% or more, which is a recognized threshold for kidney disease progression, the researchers noted.
The rate of eGFR change over time showed the fastest improvement during the first 26 weeks of treatment, remained positive through week 52, and then stabilized to week 104. Participants who switched from the placebo to Yorvipath after week 26 showed eGFR improvements similar to those of participants who had been on the drug from the start, the data showed.
High levels of calcium in the urine (hypercalciuria) are a known complication in hypoparathyroidism managed with conventional therapy, as excess calcium passing through the kidneys can cause damage over time. Elevated mean 24-hour urine calcium levels normalized within 26 weeks of Yorvipath and remained normalized through week 104, the results showed.
Minimal side effects seen with Yorvipath use over 2 years
Most treatment-related side effects were mild or moderate in severity. The most commonly reported treatment-related adverse events through week 104 were injection site reactions (26.3%), high blood calcium (13.8%), nausea (8.8%), low blood calcium (7.5%), and headache (7.5%). Postural orthostatic tachycardia syndrome, a condition involving an abnormal increase in heart rate and dizziness upon standing, was seen for some patients.
Overall, “these data … underscore the generalized benefit of this form of PTH replacement therapy for those suffering from chronic hypoparathyroidism and its biochemical abnormalities and clinical manifestations,” the researchers wrote.
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