The FDA has thrown a curveball to Ascendis, bringing the company’s hypoparathyroidism drug approval request to a screeching halt less than a month before a decision was due.
The Danish drugmaker had its sites firmly set on an approval decision date of April 30, a schedule set out by the FDA back in October. At the time, the agency said it wasn’t planning to hold an advisory committee meeting to discuss the application for the hormone replacement therapy, dubbed TransCon PTH.
But now the FDA has notified Ascendis of deficiencies in the application “that at this time precludes them from holding further discussions about labeling and post-marketing requirements/commitments,” the biotech announced in a release this morning.
The issues raised were not disclosed in the FDA’s previous letter, Ascendis pointed out. The regulator also made clear that these issues don’t reflect the final decision on the application.
The biotech seems to have been assuming the therapy would cruise to approval, revealing last month that its commercial, medical affairs and product supply teams were readying themselves in both the U.S. and Europe, where product launches were expected in this quarter and early 2024, respectively.
“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,” said Ascendis CEO Jan Mikkelsen in the release. “The safety of patients remains our highest priority and, since our NDA submission, no new safety signals have been observed to date in our ongoing TransCon PTH phase 2 and phase 3 clinical trials or in our expanded access program and these programs continue unchanged.”
A review of TransCon PTH for approval in Europe “continues as expected,” Mikkelsen added, with the biotech remaining on track for a decision from the European Commission in the fourth quarter of the year.
Investors didn’t seem reassured, sending the Copenhagen-based company’s stock plummeting 38% on the Nasdaq to $66.47 from a Friday closing price of $107.22.
When it came to the FDA’s surprise response to TransCon PTH, analysts “certainly didn’t see this one coming,” Evercore’s Josh Schimmer said in a note Monday morning. “In light of the overall profile and high unmet need, our base scenario is the median delay for approved drugs post deficiencies notification of roughly one year,” Schimmer added.
Hypoparathyroidism (hypopara) is the underactivity of one or more parathyroid glands, which are responsible for producing calcium in the blood. Symptoms include muscle aches, twitching or spasms and a burning sensation in the toes, feet or lips.
TransCon PTH is designed to boost parathyroid hormones. It acts as a prodrug, meaning it begins to take effect after it’s metabolized. The therapy aced a phase 3 trial last year, improving calcium levels in nearly 80% of patients treated and lessening disease severity.
Up until today, the company had been on a home run with regulators, having secured FDA approval in 2021 for Skytrofa, a treatment for pediatric patients with an endogenous growth hormone deficiency. The following year, the therapy got the greenlight from European regulators as well.