INDICATION AND LIMITATIONS OF USE

YORVIPATH (palopegteriparatide) is indicated for the treatment of hypoparathyroidism in adults.

YORVIPATH was not studied for acute post-surgical hypoparathyroidism. YORVIPATH’s titration scheme was only evaluated in adults who first achieved an albumin-corrected serum calcium of ≥ 7.8 mg/dL using calcium and active vitamin D treatment.

This site is intended for US healthcare professionals only.

For US Patients Prescribing Information Indication/Limitations of Use

Efficacy

waves

Phase 3 Clinical Trial

Study design1

YORVIPATH study design table

Phase 3 clinical trial

The efficacy and safety of YORVIPATH were evaluated in a 26‑week, randomized, double-blind, placebo-controlled phase 3 clinical trial of 82 adult patients with hypoparathyroidism. Patients were randomized 3:1 to receive a daily subcutaneous injection of either YORVIPATH 18 mcg/day or placebo, both co-administered with conventional therapy (active vitamin D and calcium) and subsequently titrated based on serum calcium levels. All patients (n = 79) who completed the 26‑week blinded period were eligible to enroll in the 156-week open-label extension.1

The efficacy assessment was the proportion of patients who achieved all of the following at week 262:

  • Albumin-corrected serum calcium levels in the normal range (8.3 to 10.6 mg/dL)
  • Independence from conventional therapy (defined as requiring no active vitamin D and ≤ 600 mg/day of calcium supplementation,* including no use of PRN doses) since week 22
  • No increase in study drug dose since week 22
  • No missing active vitamin D and calcium data since week 22
  • Dose of study drug ≤ 30 mcg/day during the entire 26‑week treatment period†
* Elemental calcium ≤ 600 mg/day was allowed if needed to meet recommended dietary calcium intake.1,2
† The study drug dose was allowed to be titrated above 30 mcg/day in the phase 3 clinical trial, but the maximum recommended daily dose of YORVIPATH is 30 mcg/day. In the trial, patients who received a YORVIPATH dose > 30 mcg/day at any time point during the 26‑week treatment period were considered nonresponders for the efficacy assessment.1,2

Pooled baseline characteristics2

YORVIPATH baseline characteristics table

Mean baseline albumin-corrected serum calcium2:

YORVIPATH: 8.8 mg/dL

Placebo: 8.6 mg/dL

Mean baseline 24-hour urine calcium2:

YORVIPATH: 392 mg/day

Placebo: 329 mg/day

‡ Of the patients with nonsurgical hypoparathyroidism, two had autoimmune polyglandular syndrome type 1 (APS-1), one had autosomal dominant hypocalcemia type 1 (ADH1, CaSR mutation), one had DiGeorge Syndrome, and one had hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome (GATA3 mutation).2

Efficacy Assessment

Patients Taking YORVIPATH Maintained Normal Calcium With Independence From Conventional Therapy at Week 262

68.9%

(42 out of 61)

of YORVIPATH-treated patients achieved the efficacy assessment2

Versus

4.8%

(1 out of 21)

of patients who received placebo (treatment difference, 64.2%; 95% CI, 49.5% to 78.8%)2

Efficacy results for the individual components2

YORVIPATH efficacy results table
YORVIPATH efficacy results table

91.8% of YORVIPATH-treated patients had a YORVIPATH dose ≤ 30 mcg/day during the entire 26‑week treatment period2

§ Average daily standing dose of elemental calcium ≤ 600 mg, no PRN doses, and no missing data since week 22.2
II No daily standing doses, no PRN doses, and no missing data since week 22.2

Efficacy Results From the Open-label Extension Period

Efficacy results icon
  • At both week 52 and week 78, 39.3% (24 out of 61) of YORVIPATH-treated patients met the efficacy assessment2
  • Allowing for dose up-titration, the proportion of YORVIPATH-treated patients who maintained normal albumin-corrected serum calcium and independence from active vitamin D and therapeutic doses of calcium was 64% (39 out of 61) at week 52 and 66% (40 out of 61) at week 782
calcium pill bottle icon

Reduced Burden of Conventional Therapy1

Change in mean daily active vitamin D and calcium pill burden from baseline to week 261

YORVIPATH pill icon
6.7 pills/day to 0.5 pills/day
in the YORVIPATH group
placebo pill icon
6.7 pills/day to 5.4 pills/day
in the placebo group
  • All patients, including those with YORVIPATH doses > 30 mcg/day at any point during the treatment period, were included in this analysis1
safety profile icon

YORVIPATH has an established safety profile.

Learn more

INDICATION AND LIMITATIONS OF USE

YORVIPATH (palopegteriparatide) is indicated for the treatment of hypoparathyroidism in adults.

  • YORVIPATH was not studied for acute post-surgical hypoparathyroidism.
  • YORVIPATH’s titration scheme was only evaluated in adults who first achieved an albumin-corrected serum calcium of at least 7.8 mg/dL using calcium and active vitamin D treatment.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

YORVIPATH is contraindicated in patients with severe hypersensitivity to palopegteriparatide or to any of its excipients. Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been observed with parathyroid hormone (PTH) analogs.

Important Safety Information

INDICATION AND LIMITATIONS OF USE

YORVIPATH (palopegteriparatide) is indicated for the treatment of hypoparathyroidism in adults.

  • YORVIPATH was not studied for acute post-surgical hypoparathyroidism.
  • YORVIPATH’s titration scheme was only evaluated in adults who first achieved an albumin-corrected serum calcium of at least 7.8 mg/dL using calcium and active vitamin D treatment.

CONTRAINDICATIONS

YORVIPATH is contraindicated in patients with severe hypersensitivity to palopegteriparatide or to any of its excipients. Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been observed with parathyroid hormone (PTH) analogs.

WARNINGS AND PRECAUTIONS

Risk of Unintended Changes in Serum Calcium Levels Related to Number of Daily Injections

Use only one YORVIPATH injection to achieve the recommended once daily dosage. Using two YORVIPATH injections to achieve the recommended once daily dosage increases the variability of the total delivered dose, which can cause unintended changes in serum calcium levels, including hypercalcemia and hypocalcemia.

Serious Hypercalcemia

Serious events of hypercalcemia requiring hospitalization have been reported with YORVIPATH. The risk is highest when starting or increasing the dose of YORVIPATH but may occur at any time. Measure serum calcium 7 to 10 days after any dose change or if there are signs or symptoms of hypercalcemia, and at a minimum of every 4 to 6 weeks once the maintenance dose is achieved. Treat hypercalcemia if needed. If albumin-corrected serum calcium is greater than 12 mg/dL, withhold YORVIPATH for at least 2-3 days. For less serious hypercalcemia, adjust the dose of YORVIPATH, active vitamin D, and/or calcium supplements.

Serious Hypocalcemia

Serious events of hypocalcemia have been observed with PTH products, including YORVIPATH. The risk is highest when YORVIPATH is abruptly discontinued, but may occur at any time, even in patients who have been on stable doses of YORVIPATH. Measure serum calcium 7 to 10 days after any dose change or if there are signs or symptoms of hypocalcemia, and at a minimum of every 4 to 6 weeks once the maintenance dosage is achieved. Treat hypocalcemia if needed, and adjust the dose of YORVIPATH, active vitamin D, and/or calcium supplements if hypocalcemia occurs.

Potential Risk of Osteosarcoma

YORVIPATH is a PTH analog. An increased incidence of osteosarcoma (a malignant bone tumor) has been reported in male and female rats treated with PTH analogs, including teriparatide. Osteosarcoma occurrence in rats is dependent on teriparatide or PTH dose and treatment duration. Osteosarcoma has been reported in patients treated with teriparatide in the postmarketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use.

YORVIPATH is not recommended in patients who are at increased risk of osteosarcoma, such as patients with:

  • Open epiphyses. YORVIPATH is not approved in pediatric patients.
  • Metabolic bone diseases other than hypoparathyroidism, including Paget’s disease of bone.
  • Unexplained elevations of alkaline phosphatase.
  • Bone metastases or a history of skeletal malignancies.
  • History of external beam or implant radiation therapy involving the skeleton.
  • Hereditary disorders predisposing to osteosarcoma.

Instruct patients to promptly report clinical symptoms (e.g., persistent localized pain) and signs (e.g., soft tissue mass tender to palpation) that could be consistent with osteosarcoma.

Orthostatic Hypotension

Orthostatic hypotension has been reported with YORVIPATH. Associated signs and symptoms may include decreased blood pressure, dizziness (including postural dizziness), palpitations, tachycardia, presyncope, or syncope. Such symptoms can be managed by dosing at bedtime, while reclining. YORVIPATH should be administered initially when the patient can sit or lie down due to the potential of orthostatic hypotension.

Risk of Digoxin Toxicity with Concomitant Use of Digitalis Compounds

YORVIPATH increases serum calcium, and therefore, concomitant use with digoxin (which has a narrow therapeutic index) may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy may be reduced if hypocalcemia is present. When YORVIPATH is used concomitantly with digoxin, measure serum calcium and digoxin levels routinely, and monitor for signs and symptoms of digoxin toxicity. Refer to the digoxin prescribing information for dose adjustments, if needed.

ADVERSE REACTIONS

The most common adverse reactions (≥ 5%) in patients treated with YORVIPATH were injection site reactions (39%), vasodilatory signs and symptoms (28%), headache (21%), diarrhea (10%), back pain (8%), hypercalcemia (8%) and oropharyngeal pain (7%).

DRUG INTERACTIONS

Drugs Affected by Serum Calcium

Digoxin: YORVIPATH increases serum calcium, therefore, concomitant use with digoxin (which has a narrow therapeutic index) may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy may be reduced if hypocalcemia is present. When YORVIPATH is used concomitantly with digoxin, measure serum calcium and digoxin levels, and monitor for signs and symptoms of digoxin toxicity. Adjustment of the digoxin and/or YORVIPATH dose may be needed.

Drugs Known to Affect Serum Calcium

Drugs that affect serum calcium may alter the therapeutic response to YORVIPATH. Measure serum calcium more frequently when YORVIPATH is used concomitantly with these drugs, particularly after these drugs are initiated, discontinued, or dose adjusted.

USE IN SPECIFIC POPULATIONS

Pregnancy

Available data from reports of pregnancies in the clinical trials from drug development are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. If YORVIPATH is administered during pregnancy, or if a patient becomes pregnant while receiving YORVIPATH, healthcare providers should report YORVIPATH exposure by calling 1‑844‑442‑7236.

Lactation

Monitor infants breastfed by females treated with YORVIPATH for symptoms of hypercalcemia or hypocalcemia. Consider monitoring serum calcium in the breastfed infant.

You are encouraged to report side effects to FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Ascendis Pharma at 1‑844‑442‑7236.

Please click here for full Prescribing Information for YORVIPATH.

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