FDA Approves Ascendis’ Hypoparathyroidism Drug After Delays

Rare Daily Staff

The U.S. Food and Drug Administration approved Ascendis’ Yorvipath for the treatment of adults with the rare endocrine disorder hypoparathyroidism.

The approval follows a decision by the FDA to extend the review time for Yorvipath in May because of additional information the company submitted that the agency said constituted a major amendment to the application. In May 2023, the FDA rejected the company’s first attempt to secure approval for the drug because of concerns it had over the company’s manufacturing control strategy.

It comes as Takeda is expected to discontinue global production of its hypothyroidism drug Natpara at the end of 2024 because of supply issues.

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 to 80 percent), while other causes include autoimmune and unknown causes.

Yorvipath is a prodrug of parathyroid hormone (PTH) administered once daily. It is designed to provide continuous exposure to released PTH over a 24-hour dosing period. Current standard of care treatment with calcium and calcitriol does not effectively address both the short-term symptoms of low calcium in the blood and long-term complications of calcium deposits in the organs, or the quality-of-life impacts of hypoparathyroidism.

“The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating,” said Lynn Kohlmeier, 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 United States in the fourth quarter of 2024.

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