Yorvipath use in hypoparathyroidism shows benefits over 3 years in trial
Hormone replacement therapy leads to better calcium control for patients
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Treatment for at least three years with Yorvipath (palopegteriparatide), an approved daily hormone replacement therapy used to help manage blood calcium levels in adults with hypoparathyroidism, led to sustained improvements in calcium control for patients taking part in a clinical trial.
New results from the Phase 3 study, dubbed PaTHway (NCT04701203), and its extension, show that the therapy continues to replicate parathyroid hormone’s actions over the long term, meeting key outcome measures. The researchers also noted that treatment had beneficial effects on the kidney, small intestine, bones, and central nervous system (the brain and spinal cord).
These data reinforce earlier results from the study and extend evidence of durable disease management with Yorvipath, according to the team.
“With its unique ability to replicate the systemic actions of endogenous [the body’s own] parathyroid hormone, [Yorvipath] has successfully addressed the physical and psychological burdens of hypoparathyroidism for the majority of treated patients,” Aliya Khan, MD, professor at McMaster University in Canada, said in a press release from Ascendis Pharma, the company that markets Yorvipath.
The researchers also noted that Yorvipath — which normalized and stabilized patients’ calcium and phosphate levels over the three years of treatment — improved quality of life for the study’s participants. Further, it enabled patients to stop taking vitamin D and calcium supplements, which is the conventional approach to treating hypoparathyroidism but requires long-term use.
Hypoparathyroidism is characterized by low levels of the parathyroid hormone (PTH), which helps regulate calcium and phosphorus in the body. Yorvipath, previously known as TransCon PTH, is an approved daily hormone replacement therapy that aims to ease symptoms in adults with the rare condition.
The therapy’s approval in the U.S. in 2024 was supported by findings from the Phase 2 PaTH Forward trial (NCT04009291) and the PaTHway study.
PaTHway enrolled 82 adults with hypoparathyroidism who received Yorvipath or a placebo for about six months. After completing the trial, patients could enter the three-year extension, during which all participants received the medication.
Over 85% of those in trial had normal calcium levels after 3.5 years
The new data show that after 3.5 years of treatment with Yorvipath, 86% of patients had normal calcium levels, no longer required active vitamin D supplements, and were taking calcium supplements at doses of 600 mg/day or less. Individual analysis of these parameters demonstrated that no patient required vitamin D supplementation, and 96% achieved a 600 mg/day or lower calcium dose.
Additionally, patients maintained significant improvements in kidney function. Among those initially treated with Yorvipath, increases and subsequent stabilization were seen in the mean estimated glomerular filtration rate (eGFR), a measure of kidney function. A similar effect was observed in patients initially given the placebo who later switched to Yorvipath. This contrasted with the typical age-related decline in eGFR in healthy adults, the company noted.
Participants also showed sustained normalization of bone mineral density, a measure of bone health. Improvements were also seen for 3.5 years in patient-reported symptoms and health-related quality of life. That included physical and cognitive symptoms, as well as impacts on physical functioning and daily life.
The treatment was generally well tolerated, with no new safety signals identified until the end of the study. Adverse events were mostly mild or moderate, and no treatment discontinuations were related to Yorvipath. No patients developed antibodies against the therapeutic PTH hormone.
“Regardless of disease origin, [Yorvipath] has normalized key biochemistries and skeletal health while significantly improving kidney function and quality of life beginning at the earliest timepoints and continuing through multiple years of treatment,” said Aimee Shu, MD, Ascendis’ executive vice president and chief medical officer.
In another press release, the company shared five-year data from the Phase 2 trial. Safety and efficacy results were generally consistent with those observed in the long-term analysis of the Phase 3 study. One patient developed anti-PTH antibodies, which were transient and did not limit the treatment’s benefits.
These data demonstrate the consistent, long-term benefits of this therapy and reinforce its potential as the emerging standard of care for the treatment of hypoparathyroidism.
The Phase 2 data were presented at the European Congress of Endocrinology (ECE), in Prague by Andrea Palermo, MD, PhD, an endocrinologist at Campus Bio-Medico University in Italy.
“Moving from symptom management to addressing the underlying hormone deficiency requires normalization of PTH biology to mitigate the multi-organ impacts of hypoparathyroidism,” Palermo said, adding that Yorvipath “has achieved this, meeting the high bar for the treatment of chronic hypoparathyroidism.”
According to Palermo, “these data demonstrate the consistent, long-term benefits of this therapy and reinforce its potential as the emerging standard of care for the treatment of hypoparathyroidism.”
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