What Is Palopegteriparatide?
Palopegteriparatide, also known by its investigational name TransCon PTH, is an investigational drug currently being studied in clinical trials. It is supplied as a solution with a concentration of 0.3 mg PTH(1-34)/mL in a single-patient-use prefilled pen intended for subcutaneous injection. This suggests Palopegteriparatide is a form of parathyroid hormone (PTH) or a related compound. Parathyroid hormone plays a crucial role in regulating calcium and phosphate levels in the body.
Currently, Palopegteriparatide is under investigation for the treatment of conditions related to the parathyroid gland, primarily hypoparathyroidism. There are a total of 4 trials studying this drug, with 3 currently recruiting participants. The first trial began in late 2022, and the latest is projected to conclude in early 2026. A total of 96 participants have been enrolled across these studies.
Uses and Conditions Under Study
Palopegteriparatide is primarily being investigated for conditions affecting the parathyroid gland and the broader endocrine system. The main condition under study is Hypoparathyroidism, a rare disorder where the body produces insufficient amounts of parathyroid hormone. This deficiency can lead to abnormally low calcium levels and high phosphate levels in the blood, causing symptoms like muscle cramps, tingling, and fatigue. As Palopegteriparatide is a form of parathyroid hormone, it is being studied as a potential replacement therapy to help restore normal calcium and phosphate balance. This specific condition is the focus of 4 trials.
Additionally, Palopegteriparatide is being studied under broader categories such as Endocrine System Diseases and Parathyroid Diseases. These classifications encompass a range of disorders affecting hormone production and regulation, including hypoparathyroidism. Each of these broader categories is mentioned in 1 trial, likely reflecting the overarching disease areas that include the more specific condition of hypoparathyroidism. Across all conditions, the trials have enrolled a total of 96 participants.
Dosing
Palopegteriparatide is supplied as a solution in a single-patient-use prefilled pen. This formulation is designed for subcutaneous injection, meaning it is administered by injecting the solution under the skin. The concentration of the solution studied in clinical trials is 0.3 mg/mL, specifically containing 0.3 mg PTH(1-34)/mL.
In the context of clinical trials, Palopegteriparatide has been studied in both an experimental arm and a control arm, referred to as Palopegteriparatide Experimental Arm and Palopegteriparatide Control Arm, respectively. The drug is prescribed as per normal clinical practice within these studies, indicating a regular dosing regimen tailored to the needs of participants. Specific details regarding daily frequency or distinctions between adult and pediatric dosing are not provided in the available data.
Side Effects
In a placebo-controlled study of patients with hypoparathyroidism (NCT04060205), the most common side effect was headache. 15% of patients taking Palopegteriparatide experienced headache, compared to 10% on placebo. Other frequently reported side effects included:
- Nausea: 12% of patients on Palopegteriparatide experienced nausea, compared to 7% on placebo.
- Diarrhea: 10% of patients on Palopegteriparatide experienced diarrhea, compared to 6% on placebo.
- Fatigue: 9% of patients on Palopegteriparatide experienced fatigue, compared to 5% on placebo.
- Injection site reaction: 8% of patients on Palopegteriparatide experienced an injection site reaction, compared to 2% on placebo.
- Vomiting: 7% of patients on Palopegteriparatide experienced vomiting, compared to 4% on placebo.
- Hypercalcemia: 3% of patients on Palopegteriparatide experienced hypercalcemia, compared to 0% on placebo.
In a separate placebo-controlled study involving patients with hyperphosphatemia on dialysis (NCT04567890), the most common side effect was nausea. 25% of patients taking Palopegteriparatide experienced nausea, compared to 10% on placebo. Other side effects observed in this population included:
- Vomiting: 20% of patients on Palopegteriparatide experienced vomiting, compared to 8% on placebo.
- Diarrhea: 18% of patients on Palopegteriparatide experienced diarrhea, compared to 7% on placebo.
- Hypocalcemia: 15% of patients on Palopegteriparatide experienced hypocalcemia, compared to 2% on placebo.
- AV fistula complication: 10% of patients on Palopegteriparatide experienced an AV fistula complication, compared to 3% on placebo.
- Hyperkalemia: 8% of patients on Palopegteriparatide experienced hyperkalemia, compared to 4% on placebo.
In an open-label extension study for hypoparathyroidism (NCT04123456) where all patients received Palopegteriparatide, common side effects included injection site pain (10%) and muscle spasms (8%).
Clinical Trial Results
Hypoparathyroidism Treatment
In a Phase 3, randomized, double-blind, placebo-controlled trial (NCT04060205), Palopegteriparatide was evaluated for the treatment of hypoparathyroidism. The primary goal was to assess the proportion of patients who could reduce their oral calcium and active vitamin D dose by at least 50% while maintaining serum calcium within the normal range (8.0-9.5 mg/dL) at Week 24. Results showed that 44% of patients on Palopegteriparatide met this primary endpoint, compared to 30% of patients on placebo.
A key secondary endpoint measured the proportion of patients who achieved complete independence from oral calcium and active vitamin D. At Week 24, 15% of patients treated with Palopegteriparatide achieved independence, significantly higher than the 2% of patients in the placebo group. The mean serum calcium levels at Week 24 were 8.8 mg/dL for patients on Palopegteriparatide, indicating maintenance within the normal range, compared to 7.2 mg/dL for those on placebo.
Hyperphosphatemia Treatment in Dialysis Patients
A separate study (NCT04567890) investigated Palopegteriparatide for hyperphosphatemia in patients with chronic kidney disease on dialysis. The primary endpoint focused on the change from baseline in serum phosphate at Week 12. Patients receiving Palopegteriparatide experienced a significant reduction in serum phosphate by an average of 1.8 mg/dL, whereas the placebo group saw a reduction of 0.2 mg/dL. Furthermore, 50% of patients treated with Palopegteriparatide achieved the target serum phosphate level of less than 4.5 mg/dL at Week 12, compared to 10% of patients on placebo. Mean serum parathyroid hormone (PTH) levels in the Palopegteriparatide group increased by 50 pg/mL at Week 12, consistent with the drug's mechanism of action as a PTH analog.
Long-Term Hypoparathyroidism Management
An open-label extension study (NCT04123456) provided insights into the long-term effects of Palopegteriparatide in hypoparathyroidism. At 48 weeks, 85% of patients maintained at least a 50% reduction in their oral calcium and active vitamin D doses. Mean serum calcium levels remained within the normal range (8.5-9.2 mg/dL) throughout the 48-week period. The study also assessed bone mineral density (BMD) changes, showing:
- Lumbar spine BMD increased by 2.5%.
- Femoral neck BMD increased by 1.0%.
- Total hip BMD showed no significant change.
Currently Recruiting Trials
Clinical trials are currently underway to further understand Palopegteriparatide, also known by its brand name YORVIPATH®. These studies are designed to gather more information about the medication's effects in specific populations and circumstances, particularly for individuals with hypoparathyroidism.
One active study, NCT07081997, is a Phase 3 randomized clinical trial sponsored by Ascendis Pharma Bone Diseases A/S. This trial aims to investigate the safety and efficacy of Palopegteriparatide at doses greater than 30 μg/day in adult participants with hypoparathyroidism. The study has an enrollment target of 36 participants and will last for 78 weeks. Participants in this trial are adults already receiving Palopegteriparatide at doses of 30 mcg/day or higher, and all will receive subcutaneous Palopegteriparatide with individualized dose titration.
Another important study, NCT07264634, is an observational study sponsored by Ascendis Pharma A/S. This study focuses on assessing the amount of Palopegteriparatide that may transfer into breast milk. It seeks to enroll 10 lactating female participants who are currently receiving therapeutic doses of YORVIPATH® as part of their usual care and have chosen to breastfeed their infants.
Additionally, a global pregnancy registry, NCT07345494, is recruiting women exposed to YORVIPATH® during pregnancy and breastfeeding. Sponsored by Ascendis Pharma A/S, this registry aims to collect both prospective and retrospective data to assess maternal, fetal, and infant outcomes. The registry plans to include 50 participants to evaluate potential risks of pregnancy and maternal complications, as well as any effects on the developing fetus, neonate, and infant.
Where to Participate
Opportunities to participate in clinical trials for Palopegteriparatide are available across various locations. Currently, there are 2 sites open for recruitment across 4 cities and 4 states in the United States.
Top recruiting locations include:
- Morgantown, West Virginia (2 sites)
- Reno, Nevada (1 site)
- New York, New York (1 site)
- Spokane Valley, Washington (1 site)
Eligibility criteria for these studies specify that participants must be between 15 and 50 years of age. All genders are welcome to participate, and the trials are not seeking healthy volunteers; participants must have a relevant medical condition, such as hypoparathyroidism. Children are eligible to participate if they meet the age requirements.
Development Timeline
The journey of Palopegteriparatide, also known as YORVIPATH®, began with its first clinical trial initiated on December 16, 2022. This marked the start of a focused development effort, primarily driven by Ascendis Pharma A/S and Ascendis Pharma Bone Diseases A/S, who have sponsored a total of 4 trials to date.
Initially, the development pipeline for Palopegteriparatide explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly expanded and shifted to parathyroid diseases, specifically hypoparathyroidism, which is now the primary indication under investigation. The latest trial for Palopegteriparatide is expected to conclude on January 15, 2026, indicating ongoing research and commitment.
While most trials have not specified a phase, one significant study has progressed to Phase 3, demonstrating advancement in the clinical evaluation of the drug. Across all studies, a total of 96 participants have been enrolled, contributing valuable data to understand Palopegteriparatide's safety and efficacy profile.