Yorvipath Palopegteriparatide 168 ug/.56mL Injection, Solution — NDC 73362-100-01 (Billing 73362-0100-01)

1 INDICATIONS AND USAGE YORVIPATH is indicated for the treatment of hypoparathyroidism in adults. YORVIPATH is a parathyroid hormone analog (PTH(1-34)) indicated for the treatment of hypoparathyroidism in adults. ( 1 ) Limitations of Use : Not studied for acute post-surgical hypoparathyroidism.

( 1 ) Titration scheme 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. ( 1 ) Limitations of Use 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 [see Dosage and Administration (2.3 , 2.4) and Clinical Studies (14) ] .

2 DOSAGE AND ADMINISTRATION Use only one injection to achieve the once daily recommended dosage. ( 2.1 ) Maximum recommended YORVIPATH dosage is 30 mcg subcutaneously once daily. ( 2.1 ) Individualize YORVIPATH dosage based on serum calcium. ( 2.1 ) Refer to the Full Prescribing Information for complete dosage and administration information. ( 2 )

2.1Overview of Dosage and Monitoring Use only one injection to achieve the once daily recommended dosage. Using two injections to achieve the recommended once daily dosage increases the risk of unintended changes in serum calcium levels, including hypocalcemia and hypercalcemia [see Dosage and Administration (2.4 , 2.6) and Warnings and Precautions (5.2) ] . The maximum recommended dosage is 30 mcg subcutaneously once daily.

If an adequate response is not achieved with a maximum YORVIPATH dosage of 30 mcg, consider adding or restarting calcium and/or active vitamin D therapy and/or seek other treatment options [see Warnings and Precautions (5.2) ] . YORVIPATH's once daily subcutaneous dosage is individualized. The recommended starting dosage is 18 mcg once daily and is titrated in 3 mcg increments or decrements with the goal of maintaining serum calcium within the normal range without the need for active vitamin D (e.g., calcitriol) or therapeutic calcium doses (elemental calcium > 600 mg/day).

Calcium supplementation sufficient to meet daily dietary requirements may be continued. Advise patients to monitor daily for clinical signs and symptoms of hypocalcemia or hypercalcemia. Measure serum calcium 7 to 10 days after the first YORVIPATH dose and after any dose change in YORVIPATH, active vitamin D, or calcium supplements, and monitor for clinical signs and symptoms of hypocalcemia or hypercalcemia.

Once the YORVIPATH maintenance dosage is achieved, measure serum calcium levels at a minimum every 4 to 6 weeks or as indicated for symptoms of hypocalcemia or hypercalcemia. Adjust YORVIPATH, active vitamin D, and/or calcium supplements per Figure 1. Some patients may require an increase in the YORVIPATH dose over time to maintain the same therapeutic effect [see Clinical Studies (14) ] .

Refer to the Instructions for Use (IFU) for detailed instructions on the proper preparation and administration of YORVIPATH [see Dosage and Administration (2.6) ] .

2.2Laboratory Testing Prior to Initiation of YORVIPATH Within two weeks before the first dose of YORVIPATH, confirm serum 25(OH) vitamin D is within the normal range and albumin-corrected serum calcium is ≥ 7.8 mg/dL.

2.3Modification of Active Vitamin D and Calcium Supplements on Day of YORVIPATH Initiation or Up-titration On the day of initiation or up-titration of YORVIPATH, adjust the dose of active vitamin D and calcium supplements based on albumin-corrected serum calcium and current active vitamin D intake (Table 1). Table 1: Dosage Adjustments to Active Vitamin D (calcitriol) and Calcium Supplements Upon Initiation or Up-titration of YORVIPATH Treatment Albumin-Corrected Serum Calcium Current Active Vitamin D (calcitriol) Intake Adjust Active Vitamin D (calcitriol) Intake Adjust Calcium Supplements ≥8.3 mg/dL >1 mcg/day Reduce calcitriol dosage by ≥50% Maintain current calcium dosage ≥8.3 mg/dL ≤1 mcg/day Discontinue calcitriol Maintain current calcium dosage ≥7.8 to <8.3 mg/dL Any amount Reduce calcitriol dosage by ≥50% Maintain current calcium dosage ≥7.8 mg/dL Not currently on active vitamin D Not applicable Reduce calcium daily dosage by at least 1500 mg or discontinue If calcium supplements are needed to meet dietary requirements, continuing dietary calcium supplements at elemental dosages ≤ 600 mg/day may be considered instead of discontinuing the calcium entirely. if current calcium daily dosage is ≤1500 mg/day

2.4Recommended Dosage, Titration Scheme, and Monitoring The recommended starting dosage of YORVIPATH is 18 mcg once daily. Dosage adjustments should be made in 3 mcg increments or decrements. Do not increase the YORVI… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS Injection: Clear, colorless solution in single-patient-use prefilled pens in three presentations Table 2 displays the YORVIPATH prefilled pen presentations, strengths, labeled doses, and deliverable dose ranges. Table 2: YORVIPATH Prefilled Pen Presentations, Strengths, Labeled Doses, and Deliverable Dose Ranges Pen Type and Strength Labeled Dose (mcg) Range of Deliverable Dose Deliverable dose range at each labeled dose setting based on prefilled pen performance. Use only labeled dose for titration (refer to Figure 1).

(Minimum – Maximum) (mcg) Prefilled pen with blue push button (168 mcg/0.56 mL) 6 4.5 - 7.5 9 7.5 - 10.5 12 10.5 -

13.5Prefilled pen with orange push button (294 mcg/0.98 mL) 15 13.1 - 16.5 18 16.1 - 19.5 21 19.1 -

22.5Prefilled pen with burgundy push button (420 mcg/1.4 mL) 24 21.6 - 25.5 27 24.6 - 28.5 30 27.6 -

31.5Injection: single-patient-use prefilled pen ( 3 ) 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

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Dosage and Administration Advise patients to use only one injection to achieve the once daily recommended dosage [see Dosage and Administration (2.1) and Warnings and Precautions (5.2) ] . Advise patients that the healthcare provider may change the dose of YORVIPATH, calcium, or active vitamin D supplements based on serum calcium levels.

Advise patients to administer YORVIPATH subcutaneously to the abdomen or front of the thigh. Advise patients to rotate the injection site daily [see Dosage and Administration (2.6) ]. Adverse Reactions Hypersensitivity Reactions Advise patients that serious hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, can occur with YORVIPATH.

Advise patients to discontinue YORVIPATH and promptly seek medical attention if signs or symptoms of hypersensitivity reactions occur [see Contraindications (4) and Warnings and Precautions (5.1) ] . Risk of YORVIPATH Adverse Reactions with Use of Two Injections to Achieve the Recommended Once Daily Dosage Advise patients that 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.

Advise patients to use only one YORVIPATH injection to achieve the recommended once daily dosage [see Warnings and Precautions (5.2) ]. Serious Hypercalcemia and Serious Hypocalcemia Advise patients taking YORVIPATH to contact their healthcare provider promptly if they develop symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy, muscle weakness) or hypocalcemia, to report abrupt discontinuations in YORVIPATH dosing, and to follow recommended serum calcium monitoring [see Warnings and Precautions (5.3 , 5.4) ] .

Potential Risk of Osteosarcoma Advise patients that administration of other PTH products causes an increase in the incidence of osteosarcoma in rats. No increased risk of osteosarcoma was observed with teriparatide compared to a general population. Advise 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 [see Warnings and Precautions (5.5) ] .

Orthostatic Hypotension When initiating YORVIPATH treatment, advise patients to be prepared to immediately sit or lie down during or after administration if they feel lightheaded or have palpitations after the injection until their symptoms resolve. If these symptoms persist or worsen, advise patients to consult their healthcare provider [see Warnings and Precautions (5.6) ] . Digoxin Toxicity Advise patients to report use of a digoxin-containing medication and to follow recommended serum calcium and digoxin monitoring [see Warnings and Precautions (5.7) ] .

Pregnancy Advise females who are exposed to YORVIPATH during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to Ascendis Pharma (1-877-229-2184) [see Use in Specific Populations (8.1) ] .

MEDICATION GUIDE YORVIPATH ® (YOR-vih-path) (palopegteriparatide) injection, for subcutaneous use This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 8/2026 What is the most important information I should know about YORVIPATH? YORVIPATH may cause serious side effects, including: Allergic (hypersensitivity) reactions, including anaphylaxis .

Stop taking YORVIPATH and get medical help right away if you have any of the following symptoms of an allergic reaction: swelling of your face, lips, mouth, or tongue breathing problems fainting, dizziness, feeling lightheaded (low blood pressure) fast heartbeat itching rash hives High levels of calcium in the blood (hypercalcemia). YORVIPATH can cause some people to have higher blood calcium levels than normal. Your health care provider should check your blood calcium before you start and during your treatment with YORVIPATH.

Tell your health care provider if you have nausea, vomiting, dizziness, feeling thirsty, confusion, muscle weakness, and irregular heartbeat. Hypercalcemia is more likely to occur within the first 3 months of starting YORVIPATH, but it may occur at any time. Low levels of calcium in the blood (hypocalcemia).

People who stop using, miss, or change a dose of YORVIPATH may have an increased risk of low blood calcium levels, but hypocalcemia may occur at any time. Tell your health care provider if you have tingling in your fingertips, toes, lips or tongue, muscle spasms or cramps, oral numbness, depression, have problems thinking or remembering, abnormal heart rhythms, and seizures. Possible bone cancer (osteosarcoma).

Tell your health care provider right away if you have pain in any areas of your body that does not go away or any new or unusual lumps or swelling under your skin that is tender to touch. These are some of the signs and symptoms of osteosarcoma and your health care provider may need to do further tests. Tell your health care provider right away if you have any of these signs and symptoms of osteosarcoma, or high or low blood calcium levels.

See " What are the possible side effects of YORVIPATH? " for information about side effects. What is YORVIPATH? YORVIPATH is a prescription medicine used to treat adults with low parathyroid hormone (PTH) (hypoparathyroidism).

It is not known if YORVIPATH is safe and effective in people who have been recently diagnosed with hypoparathyroidism after surgery. It is not known if YORVIPATH is safe and effective if it is started in people with low levels of calcium in the blood. It is not known if YORVIPATH is safe and effective in children.

YORVIPATH should not be used in children and young adults whose bones are still growing. Who should not take YORVIPATH? Do not use YORVIPATH if you: have had a severe allergic reaction to palopegteriparatide or any of the other ingredients in YORVIPATH.

Ask your health care provider if you are not sure. See the end of this Medication Guide for a complete list of ingredients in YORVIPATH. Before using YORVIPATH, tell your health care provider about all of your medical conditions, including if you: are at higher risk of a type of bone cancer called osteosarcoma.

This is especially important: if you have a bone disease that increases your risk of developing osteosarcoma (including if you have Paget's disease). if a blood test shows that you have unexplained increases in bone alkaline phosphatase. if you have cancer of the bones or other cancer that has spread to your bones. if you are having or have had radiation therapy to the skeleton. if you are affected with a condition that runs in your family that can increase your chance of getting cancer in your bones. take medicines that contain digoxin. take medicines used to treat osteoporosis. take medicines that can affect calcium levels in your blood. are pregnant or plan to become pregnant.

It is not known if YORVIPATH will harm your unborn baby. Tell your health care provider if you become pregnant during… [Excerpted — this section continues on DailyMed.]

Label Content FRONT INSTRUCTIONS FOR USE Yorvipath ® (palopegteriparatide) injection, for subcutaneous use For 6, 9 or 12 mcg doses only This Instructions for Use contains information on how to inject YORVIPATH 168 mcg/0.56 mL (300 mcg/mL) prefilled pen for 6, 9 or 12 mcg doses only ascendis pharma Back Additional information If you need help, please ask your health care provider or nurse for advice or contact the Ascendis Pharma Helpline: Ascendis Pharma Helpline: Toll-free telephone number: 1-844-442-7236 Ascendis Pharma Bone Diseases A/S Tuborg Boulevard 12 DK-2900 Hellerup Denmark ascendis pharma Panel 1 1.

How often must I test the pen flow? You should only test the pen flow (Section 2) the first time you use a new pen (or if you think it might be damaged) to not waste medicine. The test checks to make sure the medicine flows through the pen so that you get the right doses of medicine.

2. I do not see drops appear after I have tested the pen flow 5 times. What should I do?

If you see no drop on the needle tip after 5 attempts it might be because there is no flow through the pen and needle. Change the needle (see Section 5, Step 12 ) and test the pen flow again (see Section 2, Steps A-C ). You can be sure the flow works correctly when you see the drop of medicine.

If it still does not work, throw away (discard) the pen and contact your health care provider. 3. How do I know I have completed the injection?

Your injection is only completed after you have pressed the push button all the way in and the dose selector has rotated back to the "•" and you have kept the needle in the skin for 5 seconds . 4. Why do I have to keep holding the pen in the skin for 5 seconds?

Some medicine might flow back into the pen or flow backward from the injection site and be left on the skin. Holding the pen in the skin for 5 seconds helps to make sure that all the medicine has been injected. 5.

I cannot dial the dose selector to the required dose. What should I do? The pen does not allow a larger dose to be set than what is left in the pen.

If your dose is larger than the amount of medicine left in the pen you will not be able to dial a full dose. You must throw away your pen and take the full dose of medicine with a new pen. Panel 2 Until first use, refrigerate your pens between 2°C to 8°C (36°F to 46°F) and keep in the package to protect from light.

After first use, store your pen for 14 days at room temperature below 30°C (86°F). Do not leave your pen in a car or another place where it can get too hot or too cold. Do not freeze your pen.

Store YORVIPATH away from heat. Keep the YORVIPATH pen out of the reach of children. Tip: You should take a new pen out of the refrigerator 20 minutes before first use to allow the medicine to get to room temperature before injecting.

Panel 3 Caring For Your Pen Handle your pen with care. Keep your pen dry. Use a moist cloth to clean your pen.

Do not drop or knock your pen against hard surfaces. If you do, test the pen flow again (Section 2, Steps A – C) before next use. Do not apply extra force to your pen.

It might be empty, damaged and no longer works properly. Do not attempt to repair a damaged pen yourself. If your pen is damaged, contact the Ascendis Pharma Helpline.

Panel 4 Important Information You Need To Know Before Using Your YORVIPATH Pen Read and follow this Instructions for Use carefully so that you inject YORVIPATH the right way. If you do not understand or are unable to complete a step that is described in this Instructions for Use, contact your health care provider or nurse or the Ascendis Pharma Helpline. Make sure you have received training from your health care provider or nurse before injecting.

This is important to make sure that you get the correct treatment. Inject YORVIPATH into the belly (abdomen) or in the front of the thigh. Your pen can deliver doses of 6, 9 or 12 mcg .

It is used for injections under the skin (subcutaneous) for daily treatment of hypoparathyroidism. Your pen is a… [Excerpted — this section continues on DailyMed.]