Palopegteriparatide Allows for PTH Tapering in Hypoparathyroidism, With Mishaela Rubin, MD, MS

Palopegteriparatide’s efficacy and safety profile for patients with hypoparathyroidism has been reaffirmed by a recent real-world analysis of patients enrolled in a US expanded access program, which also provided insight into outcomes of different treatment transition processes.1

The expanded access program was undertaken by Ascendis Pharma for the purpose of investigating patients who had previously received PTH treatment but were ineligible for an ongoing clinical trial of palopegteriparatide.2

“Overall, the results were very similar to what was seen in the more rigorous clinical trials, namely that patients were able to come off of their standard of care requirements while maintaining a normal serum calcium level,” Mishaela Rubin, MD, MS, professor of medicine at Columbia University Irving Medical Center and investigator on the expanded access program, said in an interview with HCPLive. “I think it was reassuring, taking our experience out of the very regimented scope of the clinical trial and moving it out into a real-world population.”

For inclusion in the program, these patients were also required to have a serum albumin-adjusted calcium level ≥7.8 mg/dL and 25(OH) vitamin D in the normal range for 2 weeks prior to the first dose, as well as a body mass index (BMI) 17-40 kg/m2. Patients were excluded if they were currently enrolled in an investigational drug or device study or had severe renal impairment, increased risk for osteosarcoma, active malignancy within the last 2 years, or severe or decompensated cardiac disease within 26 weeks.2

Palopegteriparatide is a prodrug of parathyroid hormone (PTH) (1-34), designed to provide active PTH within the physiological range for 24 hours daily. The PTH released from palopegteriparatide has a half-life of roughly 60 hours. Doses are given subcutaneously once daily via a prefilled pen.1

During the program, patients would receive palopegteriparatide as a solution with a concentration of 0.3 mg PTH (1-34)/mL in a prefilled pen for subcutaneous injection. Initiation and titration were guided by a protocol-specified algorithm guided by serum calcium levels. Serum calcium was measured locally 7-14 days after initiating or titrating palopegteriparatide, at a minimum of every 2 months after the maintenance dose was reached.2

Ultimately, 135 patients enrolled in the extended access program and received ≥1 dose of palopegteriparatide – of these, 123 consented to share their data and were included in the final analysis. At the data cut for the analysis, 96.7% of patients remained on palopegteriparatide treatment. Most patients were diagnosed with postsurgical hypoparathyroidism (82.1%). Investigators noted comorbidities including anxiety (13.8%), thyroid cancer not otherwise specified (10.6%), papillary thyroid cancer (9.8%), nephrolithiasis (8.9%), and chronic kidney disease (4.9%), among others.1

Of the total enrolled patients, 62 (50.4%) were classified as direct switch, which was defined as having stopped short-lived PTH therapy ≤1 day prior to palopegteriparatide initiation, including overlapping therapy. Another 61 patients were nondirect switch, defined as stopping short-lived PTH therapy ≥2 days before initiation.1

Among the direct switch patients, 80.4% (n = 41) achieved independence from conventional therapy by month 3, and all patients achieved independence by month 12. 75% of the nondirect switch patients (n = 36) achieved independence from conventional therapy by month 3, and 66.7% of the remainder achieved independence by month 12. Mean serum calcium was within the reference range at each time point, with a mean of 8.8 mg/dL (standard deviation [SD], 0.6) at month 12. Direct switch patients maintained normocalcemia over 12 months of treatment with a mean of 9.1 mg/dL (SD, 0.7) at month 3 and 9.1 mg/dL (SD, 0.6) at month 12. For nondirect switch patients, normocalcemia was maintained over 12 months with a mean of 9.3 mg/dL (SD, 0.9) at month 3 and 8.3 mg/dL (SD, 0.3) at month 12.1

Despite these positive results, however, data is still needed regarding switching hypoparathyroidism therapies. Little data exists regarding the process by which clinicians should transition from one given PTH to another.

“It’s important to ask, is there a protocol for how to stop one PTH and start the other? Should it be the same day? Should it even be overlapping by a day?” Rubin said. “We also want data about what happens when patients might need to stop palopegteriparatide. I think having more information about changes like that would be important.”

References

1. Graham T, Shoback DM, Abbott L, et al. Early U.S. Real-World Treatment Patterns and Outcomes in Palopegteriparatide Treatment for Patients With Hypoparathyroidism. Endocr Pract. 2025;31(12):1568-1575. doi:10.1016/j.eprac.2025.08.008

2. Ascendis Pharma Bone Diseases A/S. Expanded Access Program of Palopegteriparatide in Patients with Hypoparathyroidism. ClinicalTrials.gov Identifier: NCT05654701. Updated June 27, 2025. Accessed January 8, 2026. https://www.clinicaltrials.gov/study/NCT05654701