FDA Approves YORVIPATH® (Palopegteriparatide) as the First and Only Treatment for Hypoparathyroidism in Adults (2024)

Ascendis Pharma A/S (Nasdaq: ASND) today announced that the U.S.Food & Drug Administration (FDA) has approvedYORVIPATH^® (palopegteriparatide; developed as TransConPTH) for the treatment of hypoparathyroidism in adults. YORVIPATHis a prodrug of parathyroid hormone (PTH[1-34]), administered oncedaily, designed to provide continuous exposure to released PTH overthe 24-hour dosing period. Hypoparathyroidism is a rare endocrinedisease caused by insufficient levels of parathyroid hormone thatimpact multiple organs and affects an estimated 70,000 to 90,000people in the United States.

“FDA approval of our second TransCon product, YORVIPATH,reflects our values and dedication to following the science to helppatients, as well as our unwavering commitment these past years toaddressing the significant unmet medical needs of thehypoparathyroidism community in the United States,” said JanMikkelsen, Ascendis Pharma’s President and Chief Executive Officer.“We are deeply grateful to patients, clinicians, and advocates fortheir many contributions to this important milestone.”

At launch, Ascendis plans to offer a suite of patient servicesfor YORVIPATH through its U.S. Ascendis Signature Access Program(A.S.A.P.), including support navigating the treatment journey andfinancial assistance programs for eligible patients.

“FDA approval of YORVIPATH is such an important milestone forour community,”said Patty Keating, Executive Director of theHypoPARAthyroidism Association.“We are thankful that theseriousness of our condition has been understood and our voicesheard. We look forward to having this new treatment option to helpus move beyond the limits and risks of conventional therapy.”

The FDA based its approval of YORVIPATH on their review of theclinical package for TransCon PTH (palopegteriparatide) submittedwith the Company’s New Drug Application, including data from theglobal Phase 2 PaTH Forward and Phase 3 PaTHway trials.

“The consequences of hypoparathyroidism on the health andquality of life of our patients can be extraordinarilydebilitating,” said Lynn Kohlmeier, M.D., endocrinologist atSpokane Osteoporosis & Endocrinology, Chair of the MedicalAdvisory Board of the HypoPARAthyroidism Association, and aninvestigator in the PaTHway Trial. “The ability to address theunderlying cause of this disease is crucial and will be animportant advancement for our patients withhypoparathyroidism.”

Ascendis is completing manufacturing of commercial product forthe U.S. market and anticipates initial supply will be available inthe first quarter of 2025. In addition, Ascendis plans to requestFDA approval to commercialize existing manufactured product, which,if approved, could be introduced in the U.S. in the fourth quarterof 2024.

Conference Call and Webcast Information
Ascendis will host a call to review the FDA approval on Monday,August 12, 2024, at 8:00 am Eastern Time / 5:00 am Pacific Time.Those who would like to participate may access the live webcasthere, or register in advance for the teleconference here. The linkto the live webcast will also be available on the Investors &News section of the Ascendis Pharma website athttps://investors.ascendispharma.com. A replay of the webcast willbe available on this section of the Ascendis Pharma website shortlyafter conclusion of the event for 30 days.

The following information is intended for the U.S.audience only:

YORVIPATH (palopegteriparatide) Important SafetyInformation

INDICATION AND LIMITATIONS OF USE
YORVIPATH (palopegteriparatide) is indicated for the treatment ofhypoparathyroidism in adults.

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

Important Safety Information (cont’d)

CONTRAINDICATIONS
YORVIPATH is contraindicated in patients with severehypersensitivity to palopegteriparatide or to any of itsexcipients. Hypersensitivity reactions, including anaphylaxis,angioedema, and urticaria, have been observed with parathyroidhormone (PTH) analogs.

WARNINGS AND PRECAUTIONS
Risk of Unintended Changes in Serum Calcium Levels Relatedto Number of Daily Injections
Use only one YORVIPATH injection to achieve the recommended oncedaily dosage. Using two YORVIPATH injections to achieve therecommended once daily dosage increases the variability of thetotal delivered dose, which can cause unintended changes in serumcalcium levels, including hypercalcemia and hypocalcemia.

Serious Hypercalcemia
Serious events of hypercalcemia requiring hospitalization have beenreported with YORVIPATH. The risk is highest when starting orincreasing the dose of YORVIPATH but may occur at any time. Measureserum calcium 7 to 10 days after any dose change or if there aresigns or symptoms of hypercalcemia, and at a minimum of every 4 to6 weeks once the maintenance dose is achieved. Treat hypercalcemiaif needed. If albumin-corrected serum calcium is greater than 12mg/dL, withhold YORVIPATH for at least 2-3 days. For less serioushypercalcemia, adjust the dose of YORVIPATH, active vitamin D,and/or calcium supplements.

Serious Hypocalcemia
Serious events of hypocalcemia have been observed with PTHproducts, including YORVIPATH. The risk is highest when YORVIPATHis abruptly discontinued, but may occur at any time, even inpatients who have been on stable doses of YORVIPATH. Measure serumcalcium 7 to 10 days after any dose change or if there are signs orsymptoms of hypocalcemia, and at a minimum of every 4 to 6 weeksonce the maintenance dosage is achieved. Treat hypocalcemia ifneeded, and adjust the dose of YORVIPATH, active vitamin D, and/orcalcium 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 ratstreated with PTH analogs, including teriparatide. Osteosarcomaoccurrence in rats is dependent on teriparatide or PTH dose andtreatment duration. Osteosarcoma has been reported in patientstreated with teriparatide in the postmarketing setting; however, anincreased risk of osteosarcoma has not been observed inobservational studies in humans. There are limited data assessingthe risk of osteosarcoma beyond 2 years of teriparatide use.

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

• Open epiphyses. YORVIPATH is not approved in pediatricpatients.

• 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 therapyinvolving 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 tenderto 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 managedby dosing at bedtime, while reclining. YORVIPATH should beadministered initially when the patient can sit or lie down due tothe potential of orthostatic hypotension.

Risk of Digoxin Toxicity with Concomitant Use ofDigitalis Compounds
YORVIPATH increases serum calcium, and therefore, concomitant usewith digoxin (which has a narrow therapeutic index) may predisposepatients to digitalis toxicity if hypercalcemia develops. Digoxinefficacy may be reduced if hypocalcemia is present. When YORVIPATHis used concomitantly with digoxin, measure serum calcium anddigoxin levels routinely, and monitor for signs and symptoms ofdigoxin toxicity. Refer to the digoxin prescribing information fordose adjustments, if needed.

ADVERSE REACTIONS
The most common adverse reactions (≥ 5%) in patients treated withYorvipath were injection site reactions (39%), vasodilatory signsand 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, concomitantuse with digoxin (which has a narrow therapeutic index) maypredispose patients to digitalis toxicity if hypercalcemiadevelops. Digoxin efficacy may be reduced if hypocalcemia ispresent. When YORVIPATH is used concomitantly with digoxin, measureserum calcium and digoxin levels, and monitor for signs andsymptoms of digoxin toxicity. Adjustment of the digoxin and/orYORVIPATH dose may be needed.

Drugs Known to Affect Serum Calcium
Drugs that affect serum calcium may alter the therapeutic responseto YORVIPATH. Measure serum calcium more frequently when YORVIPATHis used concomitantly with these drugs, particularly after thesedrugs are initiated, discontinued, or dose adjusted.

USE IN SPECIFIC POPULATIONS
Pregnancy
Available data from reports of pregnancies in the clinical trialsfrom drug development are insufficient to identify adrug-associated risk of major birth defects, miscarriage, or otheradverse maternal or fetal outcomes. If YORVIPATH is administeredduring pregnancy, or if a patient becomes pregnant while receivingYORVIPATH, healthcare providers should report YORVIPATH exposure bycalling 1-844-442-7236.

Lactation
Monitor infants breastfed by females treated with YORVIPATH forsymptoms of hypercalcemia or hypocalcemia. Consider monitoringserum 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 effectsto Ascendis Pharma at 1-844-442-7236.

Please click here to review full Prescribing Information forYORVIPATH^® in the United States.

About Hypoparathyroidism
Hypoparathyroidism is an endocrine disease caused by insufficientlevels of parathyroid hormone (PTH), the primary regulator ofcalcium and phosphate balance in the body, acting directly on boneand kidneys and indirectly on the intestines. Individuals withhypoparathyroidism may experience a range of severe and potentiallylife-threatening short-term and long-term complications, includingneuromuscular irritability, renal complications, extra-skeletalcalcifications, and cognitive impairment. Post-surgicalhypoparathyroidism accounts for the majority of cases (70-80%),while other etiologies include autoimmune and idiopathiccauses.

About Ascendis Pharma A/S
Ascendis Pharma is applying its innovative TransCon technologyplatform to build a leading, fully integrated biopharma companyfocused on making a meaningful difference in patients’ lives.Guided by its core values of Patients, Science, and Passion,Ascendis uses its TransCon technologies to create new andpotentially best-in-class therapies. Ascendis is headquartered inCopenhagen, Denmark and has additional facilities in Europe and theUnited States. Please visit ascendispharma.com to learn more.

Forward-Looking Statements
This press release contains forward-looking statements that involvesubstantial risks and uncertainties. All statements, other thanstatements of historical facts, included in this press releaseregarding Ascendis’ future operations, plans and objectives ofmanagement are forward-looking statements. Examples of suchstatements include, but are not limited to, statements relating to(i) the potential benefits of YORVIPATH, (ii) Ascendis’expectations regarding the timing of initial commercial supply ofYORVIPATH for the U.S. market, (iii) Ascendis’ plans to request FDAapproval to commercialize existing manufactured product and thepotential timing of introduction in the U.S., if such request isapproved, (iv) Ascendis’ plans regarding a suite of patientservices, (v) Ascendis’ ability to apply its TransCon technologyplatform to build a leading, fully integrated biopharma company,and (vi) Ascendis’ use of its TransCon technologies to create newand potentially best-in-class therapies. Ascendis may not actuallyachieve the plans, carry out the intentions or meet theexpectations or projections disclosed in the forward-lookingstatements and you should not place undue reliance on theseforward-looking statements. Actual results or events could differmaterially from the plans, intentions, expectations, andprojections disclosed in the forward-looking statements. Variousimportant factors could cause actual results or events to differmaterially from the forward-looking statements that Ascendis makes,including the following: dependence on third party manufacturers,distributors and service providers for Ascendis’ products andproduct candidates; unforeseen safety or efficacy results inAscendis’ development programs or on-market products; unforeseenexpenses related to commercialization of any approved Ascendisproducts; unforeseen expenses related to Ascendis’ developmentprograms; unforeseen selling, general and administrative expenses,other research and development expenses and Ascendis’ businessgenerally; delays in the development of its programs related tomanufacturing, regulatory requirements, speed of patientrecruitment or other unforeseen delays; Ascendis’ ability to obtainadditional funding, if needed, to support its business activities;the impact of international economic, political, legal, compliance,social and business factors. For a further description of the risksand uncertainties that could cause actual results to differ fromthose expressed in these forward-looking statements, as well asrisks relating to Ascendis’ business in general, see Ascendis’Annual Report on Form 20-F filed with the U.S. Securities andExchange Commission (SEC) on February 7, 2024, and Ascendis’ otherfuture reports filed with, or submitted to, the SEC.Forward-looking statements do not reflect the potential impact ofany future licensing, collaborations, acquisitions, mergers,dispositions, joint ventures, or investments that Ascendis mayenter into or make. Ascendis does not assume any obligation toupdate any forward-looking statements, except as required bylaw.

Ascendis, Ascendis Pharma, the Ascendis Pharma logo, thecompany logo, TransCon, and YORVIPATH^®are trademarks owned by the Ascendis Pharma group. © August2024 Ascendis Pharma A/S.