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FDA Extends Review for TransCon PTH in Hypoparathyroidism to August 2024

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The FDA has extended the review period for palopegteriparatide in treatment of hyperparathyroidism in adult patients by 3 months to August 14, 2024.

The US Food and Drug Administration has extended the review period for Ascendis Pharma’s application for palopegteriparatide (TransCon PTH) in the treatment of hypoparathyroidism in adult patients by 3 months until August 14, 2024, according to a release from Ascendis Pharma.1

Announced on May 14, 2024, the FDA’s decision to extend the review period is based on the agency’s determination that information submitted in response to the NDA constituted a major amendment and comes less than a month after Ascendis Pharma announced the agent had received marketing authorization from the United Kingdom’s Medicines & Healthcare products Regulatory Agency in mid-April.1,2

“We have responded to all requests received to date from FDA and will work with the agency as they continue their review of our NDA,” said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer.1 “Adults with hypoparathyroidism in the United States, who are receiving TransCon PTH in our clinical trials and our Expanded Access Program (EAP) will continue to receive their medication, and the EAP remains open for enrollment for eligible patients. We remain committed to bringing TransCon PTH to adults with hypoparathyroidism in the United States, who face an urgent need for new treatments.”

The journey to a potential approval for palopegteriparatide has been fraught with twists and turns. After submitting their NDA in August 2022, the company announced the receipt of a Complete Response Letter from the FDA in May 2023. In this announcement, the company pointed out the FDA cited concerns related to the manufacturing control strategy for variability of delivered dose in the TransCon PTH drug/device combination product, but did not express concern about the clinical data submitted as part of the NDA package and no new preclinical studies, or Phase 3 clinical trials to evaluate safety or efficacy, were requested in the letter. In December 2023, Ascendis Pharma announced the resubmission of the NDA for palopegteriparatide, which the agency considered a complete class 2 response and set a PDUFA goal date of May 14, 2024.1,3,4,5

The basis of the application by Ascendis Pharma was phase 3 PaTHway trial. A randomized, double‐blind, placebo‐controlled, parallel‐group trial, PaTHWAY randomized 82 adults with chronic hypoparathyroidism in a 3:1 ratio to palopegteriparatide or placebo therapy for 26 weeks.6

Results of the trial demonstrated 79% of the palopegteriparatide group achieved the primary outcome compared to 5% among the placebo group (P <.0001). Analysis of secondary outcomes of interest revealed use was also associated with significant improvement in all key secondary endpoint Hypoparathyroidism Patient Experience Scale domain scores (all P <.01) and the SF‐36 Physical Functioning subscale score (P=.0347) relative to placebo.6

Since the trial was published in the Journal of Bone and Mineral Research in January 2023, multiple analyses of the trial have come forth bringing new data and insight into the effects of the therapy, including a post-hoc analysis presented at the European Congress of Endocrinology 2024 the day prior to approval. In this analysis, results indicated use of was associated with significant and sustained improvements in renal function in adults with chronic hypoparathyroidism.7

References:

  1. Ascendis Pharma. Ascendis Pharma Announces Extension of U.S. Food and Drug Administration Review of TransCon™ PTH NDA [Internet]. Ascendis Pharma. May 14, 2024. Accessed May 14, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-pharma-announces-extension-us-food-and-drug-1.
  2. Ascendis Pharma. United Kingdom’s MHRA approves YORVIPATH® (palopegteriparatide) in Great Britain for the treatment of adults with chronic hypoparathyroidism: Ascendis Pharma. Ascendis Pharma. April 24, 2024. Accessed May 13, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/united-kingdoms-mhra-approves-yorvipathr-palopegteriparatide.
  3. Ascendis Pharma. Ascendis Pharma Submits TransconTM PTH New Drug Application to the U.S. FDA for adult patients with Hypoparathyroidism: Ascendis Pharma. Ascendis Pharma. August 31, 2022. Accessed May 13, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-pharma-submits-transcontm-pth-new-drug-application-us.
  4. Ascendis Pharma. U.S. Food & Drug Administration Issues Complete Response Letter for TransConTM PTH in Hypoparathyroidism: Ascendis Pharma. Ascendis Pharma. May 1, 2023. Accessed May 13, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/us-food-drug-administration-issues-complete-response-letter.
  5. Ascendis Pharma. FDA accepts for review resubmitted NDA for transcon PTH (palopegteriparatide) in adult patients with hypoparathyroidism: Ascendis Pharma. Ascendis Pharma. December 11, 2023. Accessed May 13, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/fda-accepts-review-resubmitted-nda-transcon-pth.
  6. Khan AA, Rubin MR, Schwarz P, et al. Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial. J Bone Miner Res. 2023;38(1):14-25. doi:10.1002/jbmr.4726
  7. Ascendis Pharma. Significant and sustained improvements in renal function reported for adults with chronic hypoparathyroidism treated with TransconTM PTH (palopegteriparatide): 2-year results from phase 3 pathway trial: Ascendis pharma. Ascendis Pharma. May 13, 2024. Accessed May 13, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/significant-and-sustained-improvements-renal-function-reported.

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