Ascendis Pharma

Ascendis Pharma: Progress and Challenges in NDA Submission

Ascendis Pharma has recently made significant progress toward the approval of its drug TransCon PTH for the treatment of chronic hypoparathyroidism. This article highlights recent developments, study results, and the company’s future steps in this complex process.

Milestones and Challenges of the NDA Submission

Initial Submission and FDA Response

In August 2022, Ascendis Pharma submitted the New Drug Application (NDA) for TransCon PTH to the FDA. In May 2023, the company received a Complete Response Letter from the FDA, raising concerns about the manufacturing strategy to control the variability of the delivered dose. However, there were no concerns regarding clinical data, new preclinical studies, or Phase 3 clinical studies on the safety or efficacy of the drug.

Resubmission of the NDA

Ascendis Pharma resubmitted the NDA in December 2023. The FDA responded with a Complete Response of Class 2, setting a PDUFA target date of May 14, 2024. Due to the response classified as a "major amendment to the NDA," the FDA extended the PDUFA date to August 14, 2024, allowing an additional three months for review.

Results of the Phase 3 PaTHway Study

The Phase 3 PaTHway study was a randomized, double-blind, placebo-controlled parallel-group study involving 82 adult participants with chronic hypoparathyroidism. The randomization ratio was 3:1 (palopegteriparatide: placebo), and the study lasted 26 weeks.

Primary and Secondary Endpoints

The results were promising: 79% of patients in the palopegteriparatide group achieved the primary endpoint, compared to only 5% in the placebo group (P < .0001). The secondary endpoints also showed significant improvements in all areas of the Hypoparathyroidism Patient Experience Scale (all P < .01) and in the SF-36 subscale score for physical function (P = .0347) compared to placebo.

Subsequent Analyses and Presentations

The study results were published in January 2023 in the Journal of Bone and Mineral Research. Subsequent analyses provided new data and insights, presented at the European Congress of Endocrinology 2024. These analyses showed significant and sustained improvements in kidney function among adults with chronic hypoparathyroidism.

Further Approvals and Market Launches

During the FDA review, TransCon PTH, marketed as Yorvipath in Europe, was approved by the EMA in November of last year and received approval in the United Kingdom in April. Ascendis has already begun the market launch in Germany and Austria.

Importance and Impact of Hypoparathyroidism

Hypoparathyroidism affects about 70,000 people in the USA. This condition leads to insufficient calcium production by the parathyroid glands, resulting in muscle discomfort, cramps, and long-term kidney complications and cognitive impairments. TransCon PTH has shown in studies that it increases calcium levels in 79% of patients and frees 95% of patients from traditional therapy with oral calcium supplements and active vitamin D.

Company Perspective and Projections

Ascendis Pharma aims for its second FDA approval within three years. The first approved drug, Skytroka, a long-acting growth hormone for children, was approved in 2021 and generated revenue of €179 million ($194 million) last year. For the current year, the company forecasts Skytroka sales between €320 million ($346 million) and €340 million ($368 million).

Conclusion

Ascendis Pharma has made significant progress in the development and approval of TransCon PTH. Despite challenges in the manufacturing process, the company shows great potential with strong clinical results and international market approvals. The coming months will be crucial as the FDA review and market launches in additional countries continue.