FDA Approves Palopegteriparatide for Hypoparathyroidism

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has granted approval to palopegteriparatide (YORVIPATH®), developed as TransCon PTH, for the treatment of hypoparathyroidism in adults.¹

Announced on August 12, 2024, by Ascendis Pharma, the FDA based approval on the review of palopegteriparatide's New Drug Application (NDA), including results from the global Phase 2 PaTH Forward and Phase 3 PaTHway trials.

Ascendis plans to complete commercial product manufacturing for the US market, with initial supply expected for the first quarter of 2025. The company also announced plans to request FDA approval to commercialize existing manufactured product – pending approval, this product could be introduced in the US in the fourth quarter of 2024.

“The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating,” said Lynn Kohlmeier, MD, an endocrinologist at Spokane Osteoporosis & Endocrinology, chair of the Medical Advisory Board of the HypoPARAthyroidism Association, and an investigator in the PaTHway Trial. “The ability to address the underlying cause of this disease is crucial and will be an important advancement for our patients with hypoparathyroidism.”

Hypoparathyroidism is a rare endocrine disease caused by insufficient levels of parathyroid hormone that can impact multiple organs.² The rare endocrine disease affects an estimated 70,000 to 90,000 people in the United States.

Administered once daily, palopegteriparatide is a prodrug of parathyroid hormone (PTH) designed to allow continuous exposure to released PTH during a 24-hour dosing period.¹

Results from the Phase 3 PaTHway trial demonstrated that 79% of patients randomized to palopegteriparatide therapy achieved a primary composite endpoint of normal serum calcium levels and independence from therapeutic levels of conventional therapy, compared with 5% in the placebo group (P <.0001).³

In the trial, palopegteriparatide was also linked to 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.

After the initial NDA submission in August 2022, Ascendis received a Complete Response Letter (CRL) from the FDA in May 2023, citing concerns related to the manufacturing control strategy for variability of delivered dose in the TransCon PTH drug/device combination product, but not the submitted clinical data.³

The company resubmitted the NDA in December 2023, which the FDA considered a complete class 2 response and set a PDUFA goal of May 2024.⁴ In May 2024, the review period for palopegteriparatide was extended by 3 months to August 2024, based on the FDA’s decision that information submitted in response to the May 2023 CRL constituted a major amendment.

“FDA approval of our second TransCon product, YORVIPATH, reflects our values and dedication to following the science to help patients, as well as our unwavering commitment these past years to addressing the significant unmet medical needs of the hypoparathyroidism community in the United States,” said Jan Mikkelsen, president and chief executive officer, Ascendis Pharma.¹

At the product launch, the company plans to offer patient services for palopegteriparatide through its US Ascendis Signature Access Program, involving support for the treatment journey and financial assistance programs for eligible individuals with hypoparathyroidism.

“FDA approval of YORVIPATH is such an important milestone for our community,” said Patty Keating, executive director of the HypoPARAthyroidism Association.¹ “We are thankful that the seriousness of our condition has been understood and our voices heard. We look forward to having this new treatment option to help us move beyond the limits and risks of conventional therapy.”

References

1. _{FDA approves YORVIPATH® (palopegteriparatide) as the first and only treatment for hypoparathyroidism in adults: Ascendis Pharma. FDA Approves YORVIPATH® (Palopegteriparatide) as the First and Only Treatment for Hypoparathyroidism in Adults | Ascendis Pharma. August 12, 2024. Accessed August 12, 2024. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-yorvipathr-palopegteriparatide-first-and-only.}
2. _{Sakane EN, Vieira MCC, Vieira GMM, Maeda SS. Treatment options in hypoparathyroidism. Arch Endocrinol Metab. 2022;66(5):651-657. doi:10.20945/2359-3997000000554}
3. _{Campbell P. FDA issues complete response letter for transcon PTH in hypoparathyroidism. HCP Live. May 1, 2023. Accessed August 12, 2024. https://www.hcplive.com/view/fda-issues-complete-response-letter-transcon-pth-in-hypoparathyroidism.}
4. _{Campbell P. FDA extends review for Transcon pth in hypoparathyroidism to August 2024. HCP Live. June 4, 2024. Accessed August 12, 2024. https://www.hcplive.com/view/fda-extends-review-for-transcon-pth-in-hypoparathyroidism-to-august-2024.}