| Drug Name |
YORVIPATH®(palopegteriparatide) |
| Active Ingredient |
palopegteriparatide |
| Date of Approval |
August 9th, 2024 |
| Manufacturer |
Ascendis Pharma, Inc. |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: YORVIPATH® is indicated
for the treatment of hypoparathyroidism in adults |
| Therapeutic Class |
parathyroid hormone analog |
| Formulation |
Injection: single-patient-use prefilled pen:
• 168 mcg/0.56 mL pen, labeled doses of 6, 9, or 12 mcg
• 294 mcg/0.98 mL pen, labeled doses of 15, 18, or 21 mcg
• 420 mcg/1.4 mL pen, labeled doses of 24, 27, or 30 mcg |
| MoA |
Palopegteriparatide releases PTH(1-34) under physiological conditions to maintain continuous systemic exposure. Like endogenous parathyroid hormone (PTH), PTH(1-34) helps regulate extracellular calcium and phosphate levels by increasing serum calcium and decreasing serum phosphate. It does so by stimulating bone turnover to release calcium and phosphate from bone, promoting calcium reabsorption and phosphate excretion in the kidneys, and enhancing the synthesis of active vitamin D, which in turn increases intestinal absorption of calcium and phosphate. These effects are mediated through the parathyroid hormone 1 receptor (PTH1R), which is primarily expressed on osteoblasts, osteocytes, renal tubular cells, and other tissues. |
| Dosing and Administration |
YORVIPATH® should be administered as a single injection once daily, with the maximum recommended dosage being 30 mcg subcutaneously. If the maximum dosage of 30 mcg does not yield an adequate response, alternative treatments or the addition of calcium and/or active vitamin D therapy should be considered.
The dosage is individualized, starting at 18 mcg daily, and can be adjusted in 3 mcg increments or decrements to maintain normal serum calcium levels without relying on active vitamin D or high therapeutic calcium doses.
Patients should monitor for signs of hypocalcemia or hypercalcemia daily. Serum calcium levels should be measured 7 to 10 days after starting YORVIPATH® or after any dose adjustments and monitored regularly every 4 to 6 weeks or as needed based on symptoms. |
| Administered by self or by HCP |
Administered by self |
| Place in Therapy |
The FDA approved YORVIPATH® for the treatment of hypoparathyroidism in adults, with the therapy being the first and only approved treatment in the United States for hypoparathyroidism. Hypoparathyroidism is a rare endocrine disease affecting an estimated 70,000 to 90,000 people in the United States.
YORVIPATH® is a long-acting parathyroid hormone analog that releases PTH (1-34) throughout the day, which temporarily restores physiologic levels of parathyroid hormone, maintaining the balance of calcium and phosphate in the body. This addresses both the short-term symptoms and long-term complications of hypoparathyroidism.
Note to HCPs: Administer YORVIPATH® as a single daily injection to minimize dose variability. Monitor serum calcium regularly due to the risk of hypercalcemia and hypocalcemia. YORVIPATH® is not recommended for patients at high risk of osteosarcoma. Monitor for orthostatic hypotension symptoms. When used with digoxin, monitor serum calcium and digoxin levels frequently to avoid digitalis toxicity if hypercalcemia occurs. |
| Expected Market Launch Date |
First quarter of 2025 |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
ISI Evercore modeled a $150,000 to $160,000 annual price for Yorvipath |
| Product Discontinuation |
N/A |
| Clinical Trials |
A randomized, double-blind, placebo-controlled trial evaluated the efficacy of YORVIPATH® in adults with hypoparathyroidism. Participants were assigned to either YORVIPATH® or placebo, focusing on maintaining normal serum calcium levels (8.3 to 10.6 mg/dL) while reducing or eliminating active vitamin D and high-dose calcium supplements over 26 weeks. Efficacy was defined by maintaining serum calcium within the normal range, independence from conventional therapy (no active vitamin D and ≤600 mg/day calcium supplements), no dosage increase, and consistent data by Week 26.
At Week 26, 68.9% of YORVIPATH® subjects met the efficacy endpoint compared to 4.8% in the placebo group, with a treatment difference of 64.2% (95% CI: 49.5%, 78.8%). This efficacy decreased to 39.3% at Weeks 52 and 78 during the open-label extension. However, with dose adjustments, 64% maintained normocalcemia at Week 52 and 66% at Week 78. The safety profile was consistent, with manageable calcium-related adverse events like hypercalcemia and hypocalcemia. |
| Sources |
U.S. Food and Drug Administration. YORVIPATH (palopegteriparatide) Label. Available at:
https://www.accessdata.fda.gov/
drugsatfda_docs/label/2024/216490s000lbl.pdf.
Accessed August 13, 2024.
Investor's Business Daily. Ascendis Pharma's Yorvipath Approved. Available at: https://www.investors.com/news/technology/ascendis-pharma-yorvipath-approved/#:~:text=The%20company%20could%
20officially%20launch,underway%20in%20Germany%20and%20Austria. Accessed August 13, 2024.
Fierce Pharma. Ascendis Scores Hard-Fought FDA Nod for Hormone Replacement Therapy Yorvipath. Available at: https://www.fiercepharma.com/pharma/ascendis-scores-hard-fought-fda-nod-hormone-replacement-therapy-yorvipath#:~:text=In%20a%20note%20
to%20clients,1%2C500%20US%20patients%20on%20the. Accessed August 13, 2024.
Ascendis Pharma. FDA Approves YORVIPATH (palopegteriparatide), First and Only Treatment for Hypoparathyroidism. Available at: https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-yorvipathr-palopegteriparatide-first-and-only. Accessed August 13, 2024.
Drug Topics. FDA Approves First Treatment for Hypoparathyroidism in Adults. Available at: https://www.drugtopics.com/view/fda-approves-first-treatment-for-hypoparathyroidism-in-adults. Accessed August 13, 2024.
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