FDA Issues Complete Response Letter for TransCon PTH in Hypoparathyroidism

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Announced on May 1, the CRL from the FDA expressed concerns related to manufacturing control strategy, but did not express concern related to clinical data submitted as part of the NDA package for TransCon PTH.

US Food and Drug Administration logo | Credit: US Food and Drug Administration

Credit: US Food and Drug Administration

Ascendis Pharma has announced the receipt of a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) for palopegteriparatide (TransCon PTH) as a treatment for hypoparathyroidism.1

Announced on May 1, the CRL from the FDA cited concerns related to the manufacturing control strategy for variability of delivered dose in the drug/device combination product, but did not express concern about the clinical data submitted as part of the NDA package and did not request new studies or data. According to Ascends Pharma, the company will request a Type A meeting with the FDA at the soonest opportunity to determine the best path forward.1

“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.1 “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 U.S.”

The company’s announcement of the CRL receipt from the FDA comes less than a month after the company announced the FDA identified deficiencies in the NDA for palopegteriparatide in hypoparathyroidism precluding the agency from holding further discussions about labeling and post-marketing requirements/commitment on April 3, 2023. At the time of the release, Ascends noted the FDA stated this did not reflect their final regulatory decision.2

A rare disorder characterized by the underproduction of parathyroid hormone, hypoparathyroidism impacts about 70,000 people in the US, according to the National Organization for Rare Diseases. With the main causes of the disorder identified as neck surgery or family history, the current standards of care for hypoparathyroidism include calcium and vitamin D replacement.3

Designed to restore parathyroid hormone levels, TransCon PTH is billed as a once-daily hormone replacement. The agent was examined a s treatment in adults with hypoparathyroidism within the PaTHway trial, which was a randomized, double-blind, placebo-controlled trials of 82 adults. In March 2022, Ascendis Pharma announced topline data from the trial, which indicated the trial had met primary and all key secondary endpoints.4

In the trial, which had a primary composite endpoint defined as achievement of serum calcium levels in the normal range and independence from therapeutic levels of conventional therapy, 78.7% of palopegteriparatide-treated patients met the primary endpoint compared to just 4.8% of placebo-treated patients (P <.0001). Additionally, Ascendis point out use was associated with statistically significant improvements compared to control for all key secondary endpoints and there were no discontinuations related to study drug.4

According to Ascendis Pharma, the company expects a European Commission decision on its marketing authorization application during the fourth quarter of 2023 and, if approved, are planning the first EU launch in Germany in early 2024. The company also noted plans to enroll their first patient in a German early access program, if approved, during the second quarter of 2023.1
References:

  1. U.S. Food & Drug Administration Issues Complete Response Letter for TransCon™ PTH in Hypoparathyroidism: Ascendis Pharma. U.S. Food & Drug Administration Issues Complete Response Letter for TransCon™ PTH in Hypoparathyroidism | Ascendis Pharma. https://investors.ascendispharma.com/news-releases/news-release-details/us-food-drug-administration-issues-complete-response-letter. Published May 1, 2023. Accessed May 1, 2023.
  2. Ascendis Pharma provides update on regulatory reviews of TransCon PTH™ in Hypoparathyroidism: Ascendis Pharma. Ascendis Pharma Provides Update on Regulatory Reviews of TransCon PTH™ in Hypoparathyroidism | Ascendis Pharma. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-pharma-provides-update-regulatory-reviews-transcon. Published April 3, 2023. Accessed May 1, 2023.
  3. Hypoparathyroidism - symptoms, causes, treatment: Nord. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/hypoparathyroidism/. Published January 24, 2017. Accessed May 1, 2023.
  4. Ascendis Pharma A/S announces phase 3 pathway trial of transcon™ pth in adults with hypoparathyroidism met primary and all key secondary endpoints: Ascendis Pharma. Ascendis Pharma A/S Announces Phase 3 PaTHway Trial of TransCon™ PTH in Adults with Hypoparathyroidism Met Primary and All Key Secondary Endpoints | Ascendis Pharma. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-pharma-announces-phase-3-pathway-trial-transcontm-pth. Published March 13, 2022. Accessed May 1, 2023.
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