FDA Notifies Ascendis of Deficiencies in Application for Approval of Hypoparathyroidism Therapy
April 4, 2023
Rare Daily Staff
The U.S. Food and Drug Administration notified Ascendis Pharma that it has identified deficiencies in the company’s New Drug Application for TransCon PTH for the rare endocrine disorder hypoparathyroidism.
The letter notifying the company of the deficiencies did not identify what they were, but the agency said that it precludes it from holding further discussions about labeling and post-marketing requirements/commitments. The agency, however, stated that this does not reflect their final regulatory decision on the company’s application.
“This notification from FDA relates to their review of our NDA, and since the NDA deficiencies were not disclosed in the letter, we are eager to work with FDA to learn, understand, and address them,” said Jan Mikkelsen, Ascendis Pharma’s president and CEO. “This development a month from the agency’s PDUFA action date may lead to a delay in the FDA’s final regulatory decision on the TransCon PTH NDA.”
Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH), resulting in low calcium and elevated phosphate levels in the blood. HP 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.
TransCon PTH is an experimental prodrug in development for the treatment of adult patients with hypoparathyroidism. In the United States, Ascendis submitted its NDA for TransCon PTH in hypoparathyroidism in August 2022. In Europe, Ascendis submitted its Marketing Authorisation Application (MAA) for TransCon PTH in hypoparathyroidism to the European Medicines Agency in November 2022. The European Commission decision on the Company’s MAA is anticipated during the fourth quarter of 2023.
To date, 145 out of 154 clinical trial participants continue to be treated with TransCon PTH in phase 2 and phase 3 clinical trial open label extensions, including 57 patients in the phase 2 PaTH Forward Trial (> 3 years), 76 in the Phase 3 PaTHway Trial (> 2 years), and 12 in the phase 3 PaTHway Japan (> 1 year). In these studies, TransCon PTH has been generally well tolerated, with no discontinuations related to study drug.
“Knowing the serious unmet medical need that patients with hypoparathyroidism face, we will continue to make TransCon PTH available to patients participating in these ongoing clinical trials, as well as to physicians through our U.S. EAP, which remains open for enrollment for eligible adult patients previously treated with parathyroid hormone,” continued Mikkelsen. “In Europe, our regulatory review continues as expected and we remain on track for a European Commission decision in the fourth quarter. In addition, we expect to submit an application for an EAP in Germany and open it for enrollment in the second quarter of this year.”
Photo: Jan Mikkelsen, Ascendis Pharma’s president and CEO
Sign up for updates straight to your inbox.