Drug Trials Snapshots: YORVIPATH
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the YORVIPATH Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
YORVIPATH (palopegteriparatide) injection
(YOR-vih-path)
Ascendis Pharma Bone Disease Division A/S
Approval date: August 9, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
YORVIPATH is a parathyroid hormone analog that is approved for the treatment of hypoparathyroidism in adults.
Hypoparathyroidism is a disease in which there is insufficient parathyroid hormone (PTH) production, which leads to hypocalcemia (blood calcium levels that are low).
How is this drug used?
YORVIPATH is injected by the patient once daily.
Who participated in the clinical trials?
The FDA approved YORVIPATH based on evidence from one clinical trial (Study 1, NCT04701203) of 82 adults with hypoparathyroidism. The trial was conducted at 21 sites in seven countries including Canada, Denmark, Germany, Hungary, Italy, Norway, and the United States. Of the 82 patients, 30 were from the United States.
How were the trials designed?
YORVIPATH was evaluated in one randomized, placebo-controlled, phase 3 clinical trial of 26-weeks duration in 82 adults with hypoparathyroidism (Study 1, NCT04701203). During the double-blind period, subjects were randomized to either YORVIPATH (N=61) or placebo (N=21), at a starting dose of 18 µg/day, co-administered with conventional therapy (calcium and active vitamin D). Study drug and conventional therapy were subsequently titrated to maintain the albumin-corrected serum calcium levels in the normal range (8.3 to 10.6 mg/dL).
Efficacy was assessed based on the proportion of subjects who achieved all the following at Week 26:
- Albumin-corrected serum calcium in the normal range (8.3 to 10.6 mg/dL),
- Independence from conventional therapy (defined as requiring no active vitamin D and no more than 600 mg/day of calcium supplementation) since Week 22,
- No increase in the study drug dose since Week 22,
- No missing active vitamin D and calcium data since Week 22, and
- Study drug dose of 30 µg or less once daily during the 26-week treatment period.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were in the clinical trial used to evaluate the efficacy and safety of YORVIPATH.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trial used to evaluate the efficacy and safety of YORVIPATH.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy and safety of YORVIPATH.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy and safety of YORVIPATH.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics
| Demographic | YORVIPATH N=61 |
Placebo N=21 |
|---|---|---|
| Sex, n (%) | ||
| Female | 46 (75.4) | 18 (85.7) |
| Male | 15 (24.6) | 3 (14.3) |
| Age, years | ||
| Mean (SD) | 49.0 (13.1) | 47.3 (11.4) |
| Median (min, max) | 50.0 (19.0, 75.0) | 44.0 (34.0, 78.0) |
| Age groups, years, n (%) | ||
| <65 | 53 (86.9) | 19 (90.5) |
| ≥65 | 8 (13.1) | 2 (9.5) |
| Race, n (%) | ||
| White | 57 (93.4) | 19 (90.5) |
| Asian | 3 (4.9) | 2 (9.5) |
| Other | 1 (1.6) | 0 |
| Ethnicity, n (%) | ||
| Not Hispanic or Latino | 57 (93.4) | 18 (85.7) |
| Not reported | 3 (4.9) | 1 (4.8) |
| Unknown | 1 (1.6) | 2 (9.5) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
More patients treated with YORVIPATH were able to maintain normal serum calcium levels without needing active vitamin D and high doses of calcium supplements compared to those who were treated with placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results, Efficacy Population
Parameter |
YORVIPATH N=61 n (%) |
Placebo N=21 n (%) |
Response Rate Difference (95% CI) |
|---|---|---|---|
| Overall response at Week 26 | 42 (68.9) | 1 (4.8) | 64.2 (49.5, 78.8) |
| Response for each component | |||
| Normal albumin-corrected serum calciuma | 49 (80.3) | 10 (47.6) | 32.7 (9.2, 56.3) |
| Independence from active vitamin Db | 58 (95.1) | 5 (23.8) | 71.3 (52.5, 90.2) |
| Independence from therapeutic dose of calciumc | 53 (86.9) | 1 (4.8) | 82.2 (70.0, 94.4) |
| No increase in study drug dose since Week 22d | 57 (93.4) | 12 (57.1) | 36.4 (14.2, 58.5) |
| Study drug dose ≤30 µg/day up to Week 26e | 56 (91.8) | NA | NA |
Source: YORVIPATH Prescribing Information
a Normal range for albumin-corrected serum calcium was 8.3 to 10.6 mg/dL.
b No daily standing doses of active vitamin D, no PRN doses, and no missing active vitamin D data within four weeks prior to Week 26 visit.
c Average daily standing dose of elemental calcium ≤600 mg, no PRN doses, and no missing calcium data within four weeks prior to Week 26 visit.
d No increase in study drug dose within four weeks prior to Week 26 visit.
e Subjects who received more than 30 µg/day at any timepoint during the 26-week treatment period were considered as non-responders for the efficacy endpoint.
Abbreviations: CI, confidence interval; NA, not applicable; PRN, pro re nata
The proportion of subjects randomized to YORVIPATH who met the efficacy endpoint decreased over time as follows: 68.9% (42/61) at Week 26 and 39.3% (24/61) at both Week 52 and Week 78 during the open-label extension period. Allowing for dose up titration, the proportion of subjects who were able to maintain normal calcium levels without needing active vitamin D and high doses of calcium was 64% (39/61) at Week 52 and 66% (40/61) at Week 78.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The observed effect of YORVIPATH was larger for females than males. Because of limited data, this difference may be due to chance.
- Race: The number of patients of races other than White was small; therefore, differences in how YORVIPATH worked among races could not be determined.
- Age: The number of patients 65 years of age and older was small; therefore, differences in how YORVIPATH worked among ages could not be determined.
- Ethnicity: The number of patients of ethnicity other than not Hispanic or Latino was small; therefore, differences in how YORVIPATH worked among ethnic groups could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Efficacy Results by Subgroup, Efficacy Population
| Subgroup | YORVIPATH N=61 n/Ns (%) |
Placebo N=21 n/Ns (%) |
YORVIPATH Shrinkage Response Rate Posterior Mean (95% CI) |
|---|---|---|---|
| Sex | |||
| Female | 34/46 (73.9) | 1/18 (5.6) | 71.1 (57.4, 83.3) |
| Male | 8/15 (53.3) | 0/3 (0.0) | 61.7 (37.6, 79.9) |
Source: Adapted from FDA Review
Shrinkage for YORVIPATH arm was conducted with a Bayesian logistic regression model with a random effect for the subgroup. The patient’s response status was modeled using a Bernoulli random variable where the log odds of probability of success 𝛽 follows 𝑁(𝜇, 𝜎2), with prior 𝜇~𝑁(0, 5) and 1/𝜎2~𝐺amma(0.001, 0.001).The response rate was obtained by the inverse logit transformation of 𝛽.
Abbreviations: CI, credible interval; N, number of patients in the treatment arm; n, number of patients meeting the efficacy endpoint; Ns, total number of patients for each subgroup assigned to that specific arm
What are the possible side effects?
Serious side effects of YORVIPATH include a risk of high levels of calcium in the blood (hypercalcemia), low levels of calcium in the blood (hypocalcemia), bone cancer (osteosarcoma), dizziness upon standing (orthostatic hypotension), and a risk of a drug interaction with digoxin (a medicine for certain heart conditions). There is also a serious risk of unintended changes in serum calcium levels if more than one YORVIPATH injection is given daily (for this reason, only one injection of YORVIPATH should be given each day and the maximum recommended dose is 30 mg). Other side effects include injection site reactions, headache, diarrhea, back pain, and oropharyngeal (throat) pain.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Safety Results, Safety Population
Adverse Reaction |
YORVIPATH N=61 n (%) |
Placebo N=21 n (%) |
|---|---|---|
| Injection site reactionsa | 24 (39) | 1 (5) |
| Vasodilatory signs and symptomsb | 17 (28) | 0 |
| Headache | 13 (21) | 2 (10) |
| Diarrhea | 6 (10) | 1 (5) |
| Back painc | 5 (8) | 0 |
| Hypercalcemia | 5 (8) | 0 |
| Oropharyngeal pain | 4 (7) | 0 |
Source: YORVIPATH Prescribing Information
a Injection site reactions includes the preferred terms injection site bruising, injection site erythema, injection site rash, and injection site reaction.
b Vasodilatory signs and symptoms includes the preferred terms blood pressure orthostatic decreased, dizziness, dizziness postural, orthostatic hypotension, palpitations, postural orthostatic tachycardia syndrome, presyncope, syncope, and vertigo.
c Back pain includes the preferred terms back pain, flank pain, and spinal pain.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects of YORVIPATH among sex could not be determined because of limited data.
- Race: The number of patients of races other than White was small; therefore, the occurrence of side effects of YORVIPATH worked among races could not be determined.
- Age: The number of patients 65 years of age and older was small; therefore, occurrence of side effects of YORVIPATH worked among ages could not be determined.
- Ethnicity: The number of patients of ethnicity other than not Hispanic or Latino was small; therefore, the occurrence of side effects of YORVIPATH worked among ethnic groups could not be determined.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.