FDA Rejects TransCon PTH Application for Hypoparathyroidism

The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Ascendis Pharma regarding the New Drug Application (NDA) for TransCon^™ PTH (palopegteriparatide) for the treatment of adults with hypoparathyroidism.

TransCon PTH is an investigational, once-daily, long-acting prodrug of parathyroid hormone (PTH[1-34]) designed to restore physiologic levels of PTH for 24 hours. The NDA included data from the phase 3 PaTHway trial (ClinicalTrials.gov Identifier: NCT04701203) and the phase 2 PaTH Forward trial (ClinicalTrials.gov Identifier: NCT04009291), which evaluated the efficacy and safety of TransCon PTH in adults with hypoparathyroidism. The application also included data from the open-label extension studies for both trials.

In the letter, the FDA cited concerns related to the manufacturing control strategy for variability of delivered dose in the TransCon PTH drug/device combination product. No additional clinical trials to evaluate the safety or efficacy of the product were requested in the CRL.

“We are committed to working collaboratively with the FDA and, because the agency did not suggest that additional phase 3 studies may be needed to demonstrate the product’s safety and efficacy, we believe we are well prepared to address their concerns,” said Jan Mikkelsen, Ascendis Pharma’s President and CEO. “People with hypoparathyroidism need new treatment options and we are working with urgency to resolve the FDA’s concerns, with the goal of bringing TransCon PTH to patients in the US.”

Findings from the PaTHway trial showed that a statistically significantly greater proportion of patients treated with TransCon PTH met the primary endpoint achieving serum calcium levels within normal range and independence from therapeutic levels of conventional therapy compared with placebo. In the PaTH Forward trial, long-term treatment with TransCon PTH provided a durable response, with 93% of patients achieving independence from conventional therapy with active vitamin D and therapeutic levels of calcium through week 110.