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

-   Hypoparathyroidism is a rare endocrine disease with multi-organ impacts affecting an estimated 70,000 to 90,000 people in the United States

-   Ascendis to host investor conference call Monday, August 12, at 8:00 a.m. E.T.

COPENHAGEN, Denmark, Aug. 12, 2024 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (NASDAQ:ASND) today announced that the U.S. Food & Drug Administration (FDA) has approved YORVIPATH^® (palopegteriparatide; developed as TransCon PTH) for the treatment of hypoparathyroidism in adults. YORVIPATH is a prodrug of parathyroid hormone (PTH[1-34]), administered once daily, designed to provide continuous exposure to released PTH over the 24-hour dosing period. Hypoparathyroidism is a rare endocrine disease caused by insufficient levels of parathyroid hormone that impact multiple organs and affects an estimated 70,000 to 90,000 people in the United States.

"FDA approval of our second TransCon product, YORVIPATH, reflects our values and dedication to following the science to help patients, as well as our unwavering commitment these past years to addressing the significant unmet medical needs of the hypoparathyroidism community in the United States," said Jan Mikkelsen, Ascendis Pharma's President and Chief Executive Officer. "We are deeply grateful to patients, clinicians, and advocates for their many contributions to this important milestone."

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

"FDA approval of YORVIPATH is such an important milestone for our community," said Patty Keating, Executive Director of the HypoPARAthyroidism Association. "We are thankful that the seriousness of our condition has been understood and our voices heard. We look forward to having this new treatment option to help us move beyond the limits and risks of conventional therapy."

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

"The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating," said Lynn Kohlmeier, M.D., endocrinologist at Spokane Osteoporosis & Endocrinology, Chair of the Medical Advisory Board of the HypoPARAthyroidism Association, and an investigator in the PaTHway Trial. "The ability to address the underlying cause of this disease is crucial and will be an important advancement for our patients with hypoparathyroidism."

Ascendis is completing manufacturing of commercial product for the U.S. market and anticipates initial supply will be available in the first quarter of 2025. In addition, Ascendis plans to request FDA approval to commercialize existing manufactured product, which, if approved, could be introduced in the U.S. in the fourth quarter of 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 webcast here, or register in advance for the teleconference here. The link to the live webcast will also be available on the Investors & News section of the Ascendis Pharma website at https://investors.ascendispharma.com. A replay of the webcast will be available on this section of the Ascendis Pharma website shortly after conclusion of the event for 30 days.

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

YORVIPATH (palopegteriparatide) 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.

Important Safety Information (cont'd)

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 to review full Prescribing Information for YORVIPATH^® in the United States.

About Hypoparathyroidism

Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidneys and indirectly on the intestines. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune and idiopathic causes.

About Ascendis Pharma A/S

Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused 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 and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more.

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis' future operations, plans and objectives of management are forward-looking statements. Examples of such statements 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 of YORVIPATH for the U.S. market, (iii) Ascendis' plans to request FDA approval to commercialize existing manufactured product and the potential timing of introduction in the U.S., if such request is approved, (iv) Ascendis' plans regarding a suite of patient services, (v) Ascendis' ability to apply its TransCon technology platform to build a leading, fully integrated biopharma company, and (vi) Ascendis' use of its TransCon technologies to create new and potentially best-in-class therapies. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations, and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including the following: dependence on third party manufacturers, distributors and service providers for Ascendis' products and product candidates; unforeseen safety or efficacy results in Ascendis' development programs or on-market products; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen expenses related to Ascendis' development programs; unforeseen selling, general and administrative expenses, other research and development expenses and Ascendis' business generally; delays in the development of its programs related to manufacturing, regulatory requirements, speed of patient recruitment or other unforeseen delays; Ascendis' ability to obtain additional 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 risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis' business in general, see Ascendis' Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 7, 2024, and Ascendis' other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law.

Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, and YORVIPATH^® are trademarks owned by the Ascendis Pharma group. © August 2024 Ascendis Pharma A/S.

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