Ascendis Pharma A/S announced it has submitted a New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) for TransCon PTH, an investigational prodrug designed to restore parathyroid hormone (PTH [1-34]) to physiological levels over 24 hours in adult patients with hypoparathyroidism. TransCon PTH has been granted Orphan designation in the United States and European Union. The NDA is based on data from the global Phase 3 PaTHway Trial and the Phase 2 PaTH Forward Trial, as well as data from the Company's ongoing open-label extension studies for both trials.

Notably, 57 out of 59 patients continue in the open-label portion of the Phase 2 trial beyond two years of treatment, and 78 out of 79 patients continue in the open-label portion of the Phase 3 trial of TransCon PTH. In these studies, TransCon PTH has been generally well tolerated, with no discontinuations related to study drug. In the fourth quarter of this year, Ascendis Pharma plans to submit a Marketing Authorisation Application (MAA) for TransCon PTH in hypoparathyroidism to the European Medicines Agency and expects to announce topline results for Pathway Japan, the Phase 3 trial of TransCon PTH in Japan.

A phase 3 trial of TransCon PTH in hypoparathyroidism is ongoing in Greater China through VISEN Pharmaceuticals. TransCon refers to “transient conjugation.” Ascendis Pharma's proprietary TransCon platform is an innovative technology designed to create new therapies that optimize therapeutic effect, including efficacy, safety and dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two.

When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active unmodified parent drug, in a predictable manner and at predictable levels. TransCon technology is designed to be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and to be used systemically or locally.

Hypoparathyroidism is a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), resulting in low calcium and elevated phosphate levels in the blood. Hypoparathyroidism affects approximately 200,000 patients in the United States, Europe, and Japan, most of whom develop the condition following damage to or accidental removal of the parathyroid glands during thyroid surgery. Conventional treatment with calcium supplements and active vitamin D (also called calcitriol) does not effectively address the short-term symptoms, long-term complications, or quality-of-life impacts of hypoparathyroidism.

Short-term symptoms include weakness, severe muscle cramps (tetany), abnormal sensations such as tingling, burning and numbness (paresthesia), memory loss, impaired judgment, and headache. Patients often experience decreased quality of life, and, over the long term, this complex disorder can increase risk of major complications, such as calcium deposits in the brain, blood vessels, eye, and other soft tissues – including the kidneys, which can lead to impaired renal function. Hypoparathyroidism remains among the few hormonal insufficiency states without a replacement therapy that restores the missing hormone at physiologic levels.

Current standard of care with high doses of calcium and active vitamin D does not fully control the disease or address its underlying cause and may contribute to risk of renal disease. Patients with hypoparathyroidism have an estimated 4- to 8-fold greater risk of renal disease compared to healthy populations. Hypoparathyroidism is also associated with a 2-fold increased risk of depression or bipolar disorder compared to healthy populations.