FDA turns back Ascendis' hormone drug over manufacturing issues

After the FDA threw a wrench in Ascendis’ hypoparathyroidism drug application by flagging deficiencies in the filing, the agency has now issued a manufacturing-related complete response letter to the company.

In rejecting the hormone replacement therapy TransCon PTH, the agency cited concerns about Ascendis’ manufacturing control strategy for variability of delivered doses. The FDA did not find issues with the clinical data and didn’t request more studies, the company said.

“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,” Ascendis CEO Jan Mikkelsen said in a statement. Ascendis is working “with urgency” to resolve the FDA’s concerns, Mikkelsen added.

Last October, the agency said it wouldn’t hold an advisory committee meeting on the application and slated the drug for an approval decision by April 30, 2023. But, in early April, the FDA flagged “deficiencies” in the filing that prevented it from further discussing labeling and post-marketing requirements.

As regulatory talks progressed, Ascendis was gearing up for a potential launch. In the company's full-year earnings release for 2022, Ascendis said its commercial, medical affairs and product supply teams were continuing “launch readiness activities."

In Europe, the company is expecting a decision from the European Committee during the fourth quarter of this year. It plans to launch in Germany in early 2024 if all goes as planned.  

Ascendis will request a meeting with the FDA “as soon as possible to agree on the best path forward,” the company said after the recent FDA rejection.

TransCon PTH is meant to boost parathyroid hormones in patients with hypoparathyroidism, a condition in which parathyroid glands don't produce enough calcium, causing symptoms such as muscle aches and spasms. In a phase 3 trial last year, the drug improved calcium levels in nearly 78.7% of patients. In addition, 95% of patients were able to achieve independence from conventional therapy.  

In 2021, Ascendis scored its first approval with Skytrofa, a long-acting growth hormone indicated to treat children with growth hormone deficiency. The drug brought in full-year 2022 earnings of 35.7 million euros ($39.16 million).